Cancer Translational Medicine

Review | Open Access

Vol.7 (2021) | Issue-1 | Page No: 31-41

DOI: https://doi-ds.org/doilink/01.2022-28757155/CTM/01.2022-11557263/2021.V7/I1/A4

Role of PD-1/PD-L1 Inhibitors in the Treatment of Metastatic Lung Cancer

Yufei Chen1, Mei Zhong2, Zhenhua Pan2, Jun Chen2, Hongli Chen2, Fengjie Guo2, 3,*

 

 

Affiliations  

1Tianjin Key Laboratory of Optoelectronic Detection Technology and Systems, School of Life Sciences, Tiangong University, Tianjin, China;

2Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China;

3The South China University of Technology School of Medicine, Guangzhou, China

*Corresponding Author

Address for correspondence: Prof. Fengjie Guo, The South China University of Technology School of Medicine, Guangzhou Higher Education Mega Centre, Panyu District, Guangzhou 510006, Guangdong, China.E-mail address:guofengjie@scut.edu.cn 


Important Dates  

Date of Submission:   16-Nov-2021

Date of Acceptance:   27-Dec-2021

Date of Publication:   29-Dec-2021

ABSTRACT

Lung cancer is one of the most lethal solid cancers worldwide. At present, the treatment of lung cancer, especially metastatic lung cancer, is still a huge challenge. In recent years, the application of immune checkpoint inhibitors in the treatment of metastatic lung cancer therapy has become more and more mature, and the drugs mainly composed of programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), inhibitors are effective in the treatment of metastatic lung cancer. This paper summarizes the latest progress in PD-1/PD-L1 inhibitors as immunotherapy drugs in metastatic lung cancer.


INTRODUCTION

Lung cancer has one of the highest rates of morbidity and mortality among malignant tumors. According to the 2018 data of the international agency for research on cancer, lung cancer is the most common cancer and the leading cause of cancer deaths.[1] Based on the pathological classification, lung cancer can be divided into small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC) accounting for about 20% and 80%, respectively. It is hard to recognize early lung cancer by the common typical symptoms, consequently letting the patients to be diagnosed in advanced stage that increases the probability of metastasis in such patients. Chemotherapy combined with radiotherapy has good curative effects on SCLC. However, SCLC is mostly metastasized at diagnosis, resulting in relapse following treatment. There are some potential metastatic sites for lung cancer, such as bone, brain, liver, adrenal gland, etc. Brain metastasis is a significant feature of SCLC, which occurs in more than 50% of SCLC patients, in whom the quality of life and prognosis is influenced seriously.[2] Most patients with NSCLC are in the middle and advanced stage at diagnosis. The prognosis is determined by the tumor stage and the effectiveness of the treatment; however, the 5-year survival rate is still very low in NSCLC patients. About 10%-20% of NSCLC patients have brain metastasis at first diagnosis. With the advancing disease, the incidence of brain metastasis in NSCLC patients can be as high as 30%-50%.[3] The traditional treatment of metastatic lung cancer mainly focuses on surgery, chemotherapy and radiotherapy, which are harmful to the patients’ body. However, immunotherapy aims to improve the ability of biological response (including immunity), during which the patients experience least damage with maximum benefit along with longer average time to maintain the curative effect. Because of these advantages, immunotherapy has gradually gained importance in the field of lung cancer treatment and has emerged as a new treatment mode in addition to surgery, radiotherapy, chemotherapy and targeted therapy.[4] A meta-analysis involving 3025 people from five trials showed that PD-1/PD-L1 inhibitor monotherapy can significantly prolong the overall survival (OS) and progression-free survival (PFS) of NSCLC patients.[5] Another meta-analysis showed that immune checkpoint inhibitor plus chemotherapy was a more effective first-line treatment plan for patients with advanced NSCLC regardless of PD-L1 expression level.[6] In addition, compared with chemotherapy alone, chemotherapy following PD-1 inhibitor treatment is also shown to significantly improve the objective response rate (ORR).[7] The introduction of  immunotherapy has increased the 5-year survival rate of NSCLC patients to 16% - 23%, from 5% in chemotherapy treated patients.[8] In recent years, the application of PD-1/PDL1 inhibitors has become the focus of treatment for metastatic lung cancer. This paper reviews the functions and mechanisms of PD-1/PD-L1 inhibitors in metastatic lung cancer.


PD-1/PD-L1 INHIBITORS

PD-1/PD-L1 inhibitor is relatively a new drug developed for immunotherapy, which targets immune cells rather than cancer cells and is thus different from surgery, chemoradiotherapy and targeted therapy.[9] PD-1, a protein receptor located on the surface of T cells for immune regulation, is an important immunosuppressive molecule, belonging to the CD28 superfamily. PD-1 has two recognized ligands: PD-L1 (B7-H1 or CD274) and PD-L2 (B7-DC or CD273). Compared to PD-L1, the affinity of PD1 to PD-L2 is found to be 2-6 times heigher.[10] If PD-L2 were expressed at the same level as PD-L1, it would be expected to exceed PD-L1 in binding PD-1. However, because PD-L2 is usually expressed at a lower level,  PD-L1 is the preferred primary binding ligand for PD-1.[11] PD-1 combined with PD-L1 can inhibit the activation and proliferation of T cells, by down-regulating the secretion of T cell immunostimulatory cytokines to inhibit T cell immune response and promote T cell apoptosis.[12]2 When PD-L1 on the surface of tumor cells combines with PD-1 on T cells, the immune function of T cells gets turned off, resulting in immune evasion.[13],[14] The immune checkpoint inhibitors targeting PD-1/PD-L1 are shown in Figure 1.

Figure 1
Figure 1.Mechanism of action of PD-1/PD-L1 inhibitors. When PD-L1 on the surface of tumor cells is combined with PD-1 on T cells, the immune function of T cells will be turned off. The immune checkpoint inhibitors targeting PD-1 or PD-L1 can block this interaction resulting in activation of T cell.

Inhibiting the interaction of PD-1 and PD-L1 can activate T cells, causing them to effectively suppress tumor growth until the tumor cells are killed.[15] Two PD-1 inhibitors pembrolizumab (keytruda) and nivolumab (opdivo), and three PD-L1 inhibitors atezolizumab (tecentriq), durvalumab (imfinzi) and avelumab (bavencio) are being used in the treatment of lung cancer. Tislelizumab and camrelizumab are other promising PD1 inhibitors that are being studied (Table 1).

Table 1
Table 1. List of PD-1/PD-L1 inhibitors and their trade names, target, manufacturing company and the type of antibody


BIOMARKERS FOR PREDICTING EFFICACY OF PD-1/PD-L1 INHIBITORS IN LUNG CANCER

Previous clinical studies showed that PD-1/PD-L1 inhibitors are a promising treatment option for metastatic lung cancer, and have unprecedented therapeutic effects on such patients. However, a considerable number of patients gain little or no benefit after receiving PD-1/PD-L1 inhibitors. It is necessary to identify biomarkers to establish effective predictors of treatment response. It is reported that immunosuppressive molecules including PD-L1, PD-1, indoleamine 2,3-dioxygenase (IDO), and different Mismatch Repair (dMMR) have been listed as potential predictors of anti-PD-1/PD-L1 treatment response.[16] In addition, other biomarkers have also been identified, such as Tumor-infiltrating lymphocytes (TILs), immune score, TCR clonality, gene markers, plasma biomarkers(cytokines) and tumor mutation burden (TMB).[17],[18] At present, PD-L1 expression and TMB are widely used.

Many clinical studies have confirmed that the detection of PD-L1 protein expression by immunohistochemistry (IHC) is the most commonly used biomarker to predict the therapeutic efficacy of PD-1/PD-L1 inhibitors in the treatment of NSCLC.[19],[20],[21] NSCLC patients with PD-L1 expression (TPS>1%) can be treated with pembrolizumab monotherapy as first-line treatment.[22] A meta-analysis of 13 clinical trials involving 1979 patients treated with immunotherapy revealed an increased response rate in patients with PD-L1 expression (TPS>1%). Compared with PD-L1-negative, PD-L1-positive patients demonstrated a trend toward better 24-week progression-free survival and 1-year overall survival.[23] Another pembrolizumab clinical trial also showed that PD-L1-positive patients treated with immunotherapy had a better overall survival. In this study, patients whose PD-L1 expression in tumor cells exceeded 50% after pembrolizumab treatment had significantly longer overall survival and median progression-free survival (mPFS) than patients who received docetaxel. Moreover, a lower number of grade 3-5 treatment-related adverse events was observed in the pembrolizumab treatment group, as compared to the docetaxel treatment group.[24] These findings suggest that patients with PD-L1-positive lung cancer are more likely to benefit from PD-1/PD-L1 inhibitor treatment.

TMB, defined as the total number of synonymous and nonsynonymous point mutations, replacements, insertion and deletion mutations detected per million bases of somatic genes, is helpful in predicting the patient’s response to immunotherapy. TMB has thus become one of the most promising predictive biomarkers for immunotherapy.[25],[26] Rizvi et al. used whole exome sequencing (WES) to show that the therapeutic effectiveness of immunotherapy in advanced NSCLC was associated with a higher TMB.[27] Other studies have found that TMB in blood is not only linked to the efficacy of first-line immunotherapy, but also can predict the clinical efficacy of second-line immunotherapy in NSCLC patients.[28] In addition, the results of a clinical trial showed that the PFS of advanced NSCLC patients with TMB ≥ 10 mut/Mb  was significantly longer when treated with nivolumab and ipilimumab than those treated with chemotherapy alone; the 1-year progression-free survival rate was 42.6% in the nivolumab + ipilimumab group and only 13.2% in the chemotherapy group.[29] Further, the mPFS was also significantly prolonged in the nivolumab and ipilimumab group (7.2 months) compared with chemotherapy group (5.5 Months). This phase III clinical trial also confirmed for the first time that PFS of NSCLC patients with high TMB can be significantly improved by combined immunotherapeutic agents regardless of the expression level of PD-L1.


PD-1/PD-L1 INHIBITORS IN METASTATIC LUNG CANCER

The causes of high mortality of lung cancer patients are mainly attributable to malignant recurrence and distal metastasis. Lung cancer is easy to metastasize to brain, bone, liver, etc. In recent years, immune checkpoint PD-1/PD-L1 inhibitors have shown remarkable efficacy in the treatment of metastatic lung cancer.

 

Pembrolizumab

Pembrolizumab is a humanized anti-PD-1 monoclonal antibody that works by blocking PD-1 from binding to PD-L1/PD-L2, and thus activating T lymphocytes which in turn attack tumor cells. In 2015, Pembrolizumab was approved by the Food and Drug Administration (FDA) to treat patients with PD-L1 positive (TMB≥1%) metastatic NSCLC who have progressed on or after platinum-containing chemotherapy.[30]

In the KEYNOTE-189 phase-3 clinical trial involving 616 patients, who were previously untreated for metastatic non-squamous NSCLC without EGFR or ALK mutations, longer OS and PFS were shown in pembrolizumab-combination group (410 patients), as compared to placebo-combination group (206 patients).[31] In 2020 this analysis from KEYNOTE-189 was updated with the findings indicating that pembrolizumab plus pemetrexed-platinum still improved OS and PFS in metastatic non-squamous NSCLC patients with liver/brain metastases.[32]

Metastasis to the brain is typically more serious than that to bone and liver, because of the blood-brain barrier which block many drugs to pass through. Thus, systemic chemotherapy is almost ineffective in patients with brain metastasis, resulting in poor treatment outcomes. In this regard, for the first time, the KEYNOTE-001 clinical trial confirmed the efficacy of pembrolizumab on NSCLC with central nervous system metastasis. The common side effects, such as fatigue, pruritus and decreased appetite, are acceptable as they can be tolerated.  This study also showed that the efficacy of the drug was related to PD-L expression level.[33] Based on this study, the KEYNOTE-010 clinical trial evaluated the predictive value of PD-L1 expression on the efficacy of pembrolizumab, which showed that the patients expressing PD-L1>50% showed a significantly better progression-free survival to pembrolizumab treatment compared to docetaxel therapy.[24] KEYNOTE-024 clinical trial evaluated the efficacy of pembrolizumab as a first-line drug verses chemotherapy in the treatment of metastatic NSCLC. PFS and OS were significantly improved by pembrolizumab, and its side effects were less compared to chemotherapy.[34] Pembrolizumab treatment improved or maintained health-related quality-of-life (QOL) compared to platinum-based chemotherapy. In the treatment of lung cancer patients with brain metastasis, the use of a single PD-1/PD-L1 inhibitor as a second-line treatment was significantly better than the standard chemotherapy. PD-1/PD-L1 inhibitor has become the standard treatment in managing advanced NSCLC patients with brain metastasis, after the failure of the first-line chemotherapy. In addition, pembrolizumab has more advantages as the first-line treatment than other chemotherapeutic drugs.[35] In 2017, National Comprehensive Cancer Network (NCCT) indicated that pembrolizumab can be considered in patients with PD-L1-positive (≥ 50%) metastatic NSCLC as a first-line treatment.[36] Furthermore, pembrolizumab also shows activity and acceptable safety in NSCLC patients with brain metastasis, suggesting that pembrolizumab may be effective in patients with untreated or progressive brain metastasis.[37] In conclusion, these findings suggest that pembrolizumab is beneficial as the first-line and second-line treatment of lung cancer patients with brain metastasis, and provide a flexible choice for the clinical treatment. Another study evaluated the results of pembrolizumab combined chemotherapy verses chemotherapy alone in patients with PD-L1-negative advanced or metastatic NSCLC. The results demonstrated that pembrolizumab combined chemotherapy was safe, improved responsiveness and survival rate in these patients compared to chemotherapy alone. Regardless of PD-L1 expression, pembrolizumab combined with chemotherapy is the standard first-line treatment for patients with advanced NSCLC.[38]

 

Nivolumab

Nivolumab is a monoclonal antibody. As a PD-1 blocker, nivolumab can reduce the inhibitory effect of the PD-1 pathway on T cells by binding with PD-1. In 2015, FDA approved nivolumab for the treatment of metastatic or advanced NSCLC, which promoted the research of immunotherapy for metastatic lung cancer.

Zhang et al. discussed the efficacy of Nivolumab in the treatment NSCLC patients with brain metastases.[39] They collected clinical and pathological data of 22 patients with NSCLC brain metastases treated with nivolumab, and then evaluated its intracranial effect. The intracerebral ORR was 28.6%, and the intracranial disease control rate was 47.6%. The median intracranial progression-free survival of all the 22 patients was 5.2 months, and both 1-year and 2-year survival rates were 56.7%, indicating that the therapeutic effect of nivolumab on NSCLC patients with brain metastasis was similar to that of NSCLC patients without brain metastasis. Further, a study of nivolumab in progressed metastatic NSCLC patients showed a mOS of 7.8 months and mPFS of 3.7 months in these patients.[40]

In a phase Ⅰ/Ⅱ clinical study (checkmate 032), 109 SCLC patients with brain metastases received late nivolumab monotherapy or a third-line treatment. This study showed that the ORR was 11.9%, and the median duration of remission was 17.9 months. At 6 months, 17.2% of patients had no progress, and the overall survival rate at 12 and 18 months were 28.3% and 20.0%, respectively. As a third-line or late treatment for recurrent SCLC, nivolumab provides a lasting response along with a good tolerance. These results suggest that nivolumab can be effectively given as a third-line or late treatment for SCLC patients with brain metastasis.[41]

Nivolumab monotherapy, as second-line treatment, in the advanced NSCLC has been studied in three clinical trials: CheckMate 017, 057, and 063. A subgroup analysis of NSCLC patients with liver metastasis from two of these Phase Ⅲ clinical experiments (CheckMate 017 and CheckMate 057) was done to assess the effectiveness of nivolumab in such patients. The results showed that nivolumab was safe and improved OS in these patients, as compared to docetaxel, which was consistent with the results of the overall study population.[42] Further, nivolumab continued to show OS benefits after at least 3 years of follow-up in these patients. Ricciuti et al. reported a case of long-term response in lung cancer patient with liver metastasis following nivolumab, as second-line treatment, indicating that the long-term response to nivolumab (> 3 years) lasted during drug withdrawal.[43] Continuous radiological evaluation showed that during nivolumab withdrawal, not only the disease subsided, but also the tumor shrunk. This is the first case to report that the long-term response of patients with NSCLC to nivolumab continued during drug withdrawal, indicating that nivolumab is an effective treatment for advanced NSCLC.

Stimulating the immune system by targeting the PD-1/PD-L1 pathway can activate antitumor immunity. Apart from these clinical benefits, immunotherapy has also been linked to major immune-related adverse events. One study described a case of autoimmune encephalitis after PD-1 inhibitor treatment for metastatic adenocarcinoma of lung. After second-line treatment by nivolumab, the peripheral lesions subsided and the quality of life improved. Shortly thereafter, the patient developed brain injury (cerebral vasculitis), but there was no evidence of metastatic lung cancer. The analysis of the patient’s serum showed that antinuclear antibodies existed before the nivolumab treatment. In addition, it was also found that there were anti-vascular-endothelial antibodies in the serum, which showed that the patient had formed autoantibodies, inducing clinically related autoimmune diseases. In conclusion, the encephalitis of patients treated with PD-1/PD-L1 is similar to metastatic brain lesions, so it is significant to distinguish between a rare immune-related adverse event and metastatic symptoms of patients.[44] To date, studies have shown that nivolumab can provide sustained survival benefits for lung cancer patients with metastasis.

 

Atezolizumab

Atezolizumab is an IgG1 monoclonal antibody against PD-L1. As a blocker, atezolizumab can attenuate PD-1/PD-L1 mediated immunosuppression, thus promoting T cell mediated tumor suppression, by binding to PD-L1 on tumor cells and blocking its interaction with PD-1 on T cells and antigen-presenting cells. On October 18, 2016, atezolizumab was approved by FDA for the treatment of metastatic NSCLC that progress despite treating with platinum chemotherapy.

An open-label phase Ⅲ clinical study evaluated the efficacy of atezolizumab combined bevacizumab chemotherapy in patients with metastatic non-squamous NSCLC who had not received chemotherapy before. The study population included the wild-type genotype population (WT population, excluding the patients with EGFR or ALK gene changes), 336 of whom were treated with bevacizumab combining carboplatin and paclitaxel (BCP), and 356 patients were assigned to the atezolizumab and BCP (ABCP) group. The mPFS of the ABCP group was longer than that of the BCP group (8.3 months vs. 6.8 months, respectively), and the corresponding values of the WT population highly responsive to T cells were 11.3 months and 6.8 months, respectively. In WT population, the mOS of patients in the ABCP group (19.2 months) was longer than that of the BCP group (14.7 months). The study concluded that Atezolizumab combined chemotherapy can significantly improve PFS and OS in patients with metastatic non-squamous NSCLC.[45]

Another phase Ⅲ clinical study, referred to as OAK, aimed to compare atezolizumab and docetaxel in the treatment of 850 patients with advanced NSCLC. About 14% of these patients represented asymptomatic brain metastasis group, 61 of whom were in the atezolizumab group and 62 patients in the docetaxel group. Compared to docetaxel, treatment-related adverse events were less in atezolizumab group. Subgroup analysis of asymptomatic brain metastasis patients revealed a longer mOS in the atezolizumab group (16.0 months) than that in the docetaxel group (11.9 months). This result was in accordance with that of the remaining patients. Atezolizumab, apart from exhibiting OS benefit, also exhibited adequate neural safety, and compared to docetaxel, atezolizumab could prolong the time for identification of new symptomatic brain injury through imaging. This analysis showed that asymptomatic patients with brain metastases treated with atezolizumab had a lower probability of new symptomatic brain injury/lesions than with docetaxel at 6-24 months, demonstrating its neural safety and efficacy.[46]

FIR, a phase II clinical study, evaluated the safety and efficacy of atezolizumab in 138 patients diagnosed of advanced NSCLC. One cohort of the study included 13 patients with asymptomatic brain metastasis, in whom the ORR, mOS and mPFs after treatment with atezolizumab were found to be 23%, 6.8 months and 4.3 months, respectively. These results confirmed the safety and efficacy of atezolizumab monotherapy in advanced NSCLC patients with brain metastasis, which was consistent with previous trials.[47] The above studies convincingly show that NSCLC patients with asymptomatic brain metastasis can benefit from the treatment of atezolizumab.

Atezolizumab became the first immunomodulatory drug approved for the first-line treatment of SCLC, as a first step towards SCLC immunotherapy. IMPower-133 study showed that atezolizumab combined with ‘carboplatin and etoposide’ significantly improved the OS and PFS in patients with extensive-stage SCLC, as compared to those treated with ‘carboplatin and etoposide’ alone.[48] Notably, IMPower-133, for the first time, reported a significant improvement in OS compared with the current first-line standard treatment. And PCD4989g, a human phase I study, was the first to use atezolizumab in a cohort of patients with recurrent/refractory SCLC.[49] The study included 17 SCLC patients with brain metastasis, of which 65% received third-line or more treatment, and the mPFS and mOS of patients treated with atezolizumab were 1.5 months and 5.9 months, respectively. The study showed that atezolizumab, which had good tolerance and antitumor activity, improved ORR and PFS in SCLC patients with brain metastasis.

Another study pooled the results of 8 randomized controlled trials and analyzed and evaluated the effect of PD-1/PD-L1 inhibitor combined with chemotherapy as the first-line treatment for lung cancer with liver metastasis. Five of these studies focused on atezolizumab. PD-1/PD-L1 inhibitors plus chemotherapy reduced the risk of progression and death by 40% and 29%, respectively, in patients without liver metastasis, and by 31% and 21%, respectively, in patients with liver metastases. The pooled ratios of PFS-HRs and OS-HRs between lung cancer patients with liver metastasis and without liver metastasis were 1.11 and 1.03 respectively, indicating that lung cancer patients can obtain considerable curative effect by atezolizumab combined chemotherapy regardless of liver metastasis.[50]

 

Durvalumab

Durvalumab is an IgG1 monoclonal antibody, which can bind to PD-L1 on tumor cells and alleviate the immunosuppression caused by PD1/PD-L1 interaction. In Feb 2018, FDA approved durvalumab for the treatment of locally advanced unresectable NSCLC that did not progress after receiving concurrent radiotherapy and chemotherapy with a standard platinum-containing regimen.

Patients with stage III NSCLC who had no cancer progression after two or more cycles of platinum-based radiation and chemotherapy were included in a phase III clinical trial to determine the efficacy of durvalumab as consolidation therapy. This study recruited 709 patients who received consolidation treatment (473 in durvalumab and 236 in placebo group). Results showed that mPFS in the durvalumab group (16.8 months) was higher than that in the placebo group (5.6 months). The 12-month PFS rate was 55.9% in durvalumab group, but 35.3% in the placebo group. The 18-month PFS rate of the former was 44.2%, and the corresponding survival rate of the latter was 27.0%. The remission rate in the durvalumab group (28.4%) was higher than that in the placebo group (16.0%), and the median duration of remission and median time to death or distant metastasis were both longer in durvalumab group than the placebo group.[51] Another study illustrated that durvalumab combined with tremelimumab significantly improved OS or PFS compared with chemotherapy.[52]

 

Avelumab

Avelumab is a fully-humanized IgG1 monoclonal antibody targeting PD-L1. In March 2017, FDA approved avelumab for the treatment of Merck cell carcinoma, a rare skin cancer, and is recently being assessed for the treatment of metastatic lung cancer.

A study including184 patients evaluated the therapeutic efficacy of avelumab in patients with advanced NSCLC treated with platinum-based chemotherapy.[53] The results showed that 22 of these patients (1 complete remission and 21 partial remissions) achieved definite objective remission, and 70 were considered stable. In general, 92 of the 184 patients achieved disease control. Avelumab showed acceptable safety and antitumor activity in patients with progressive NSCLC. This study provided a theoretical foundation for further research of avelumab in the context of this disease.

 

Tislelizumab

Tislelizumab is a monoclonal antibody binding to the PD-1 receptor to abrogate the function of macrophages to activate T cell. RATIONALE 307 is a multicenter phase 3 trial from China, which showed that the tislelizumab in combination with chemotherapy improved the PFS in patients with metastatic squamous NSCLC.[54],[55] In another study, 54 patients with advanced or metastatic lung cancer were treated with tislelizumab in combination with platinum-doublet. The ORRs of non-squamous NSCLC, Squamous NSCLC cohort receiving paclitaxel + platinum (A) (SQ-A), or gemcitabine + platinum (B) (SQ-B) and extensive-stage SCLC were 44%, 80%, 67%, and 77% respectively. Correspondingly, median PFS in NSQ, SQ-A and SCLC were 9.0, 7.0, and 6.9 months, demonstrating an encouraging safety and efficacy of tislelizumab plus chemotherapy.[56]

 

Camrelizumab

Camrelizumab (SHR-1210) is a monoclonal antibody against PD-1. Chu Zhang et al. reported a case of lung adenocarcinoma patient with brain and spinal metastases, with a positive expression of PD-L1, treated with camrelizumab. After the failure of first-line treatment with pemetrexed/cisplatin and zoledronic acid, a complete remission of brain metastases was reportedly achieved by using camrelizumab as a second-line treatment.[57] Yan et al. reported that three patients with advanced metastatic NSCLC responded to decitabine in combination with camrelizumab with controllable adverse events.[58]


SUMMARY

As a treatment for metastatic lung cancer, PD-1/PD-L1 inhibitors, whether alone or combined with chemotherapy or other types of immune checkpoint inhibitors, have opened a new era of metastatic lung cancer treatment, and making more and more patients obtain lasting clinical benefits. However, at present, the clinical trials on metastatic lung cancer are still limited, because of the strict restriction on patients with metastatic lung cancer in clinical studies. Currently, more research is focused on basic research in the field of immunotherapy. In the future, clinical research needs to be strengthened, better treatment strategies need to be explored and formulated considering the specific characteristics of lung cancer population. In this way more patients with metastatic lung cancer will benefit from immunotherapy, in particular from PD-1/PD-L1 inhibitors.

 

Financial support and sponsorship

This work was financially supported by National Science Foundation of China (No.82070214, to Fengjie Guo).

 

Conflicts of interest

There are no conflicts of interest.


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Esther H. Chung, Hongwei Yang, Hongyan Xing, Rona S. Carroll, Mark D. Johnson


Utility of Fine Needle Aspiration Cytology in Diagnosing Bone Tumors

Sonal Mahajan1, Akash Arvind Saoji2, Anil Agrawal1


Histone H2A and H2B Deubiquitinase in Developmental Disease and Cancer

Demeng Chen1, Caifeng Dai2, Yizhou Jiang3


Genetic Characteristics of Glioblastoma: Clinical Implications of Heterogeneity

Qian Li1, Yanyang Tu1,2


Acute Lymphoblastic Leukemia with Normal Platelet Count

Khushboo Dewan, Kiran Agarwal


Galanin is a Novel Epigenetic Silenced Functional Tumor Suppressor in Renal Cell Carcinoma

Shengkun Sun1*, Axiang Xu1*, Guoqiang Yang1, Yingduan Cheng2

 


Selenium Dioxide Induced Apoptosis in Cervical Cancer Cells via Regulating Apoptosis-related Let-7a MicroRNA and Proteins

Sisun Liu1, Jieqi Xiong2, Ling Guo3, Min Xiu1,4, Feng He1,4, Yuanlei Lou5, Fei Guo6,7


Low Expression of Polo‑like Kinase 1 is Associated with Poor Prognosis in Liver Cancer

Weixia Li1, Kunpeng Liu1, Dechen Lin2, Xin Xu2, Haizhen Lu3, Xinyu Bi4, Mingrong Wang2


Extracorporeal Photopheresis for Steroid‑refractory Chronic Graft‑versus‑host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta‑Analysis

Runzhe Chen1, Baoan Chen1, Peter Dreger2, Michael Schmitt2, Anita Schmitt2


Glucans and Cancer: Historical Perspective

Petr Sima1, Luca Vannucci1, Vaclav Vetvicka2


Implications of Circadian Rhythm Regulation by microRNAs in Colorectal Cancer

Song Wu1, Andrew Fesler2, Jingfang Ju2


BCL2 Family, Mitochondrial Apoptosis, and Beyond

Haiming Dai1, X. Wei Meng2, Scott H. Kaufmann2


Quantum Dot‑based Immunohistochemistry for Pathological Applications

Li Zhou1, Jingzhe Yan2, Lingxia Tong3, Xuezhe Han4, Xuefeng Wu5, Peng Guo6


CD24 as a Molecular Marker in Ovarian Cancer: A Literature Review

Lu Huang1, Weiguo Lv2, Xiaofeng Zhao1


Etiological Trends in Oral Squamous Cell Carcinoma: A Retrospective Institutional Study

Varsha Salian, Chethana Dinakar, Pushparaja Shetty, Vidya Ajila


Effect of Irinotecan Combined with Cetuximab on Liver Function in Patients with Advanced Colorectal Cancer with Liver Metastases

Yan Liang1, Yang Li2, Xin Li3, Jianfu Zhao4


The Role of Precision Medicine in Pancreatic Cancer: Challenges for Targeted Therapy, Immune Modulating Treatment, Early Detection, and Less Invasive Operations

Khaled Kyle Wong1, Zhirong Qian2, Yi Le3


Targeting Signal Transducer and Activator of Transcription 3 for Colorectal Cancer Prevention and Treatment with Natural Products

Weidong Li1,2*, Cihui Chen3*, Zheng Liu2, Baojin Hua1


The Potential of Wnt Signaling Pathway in Cancer: A Focus on Breast Cancer

Mahnaz M. Kazi, Trupti I. Trivedi, Toral P. Kobawala, Nandita R. Ghosh


Imaging‑driven Digital Biomarkers

Enrico Capobianco


Target‑Matching Accuracy in Stereotactic Body Radiation Therapy of Lung Cancer: An Investigation Based on Four‑Dimensional Digital Human Phantom

Jing Cai1,2, Kate Turner2, Xiao Liang2, W. Paul Segars2,3, Chris R. Kelsey1, David Yoo1, Lei Ren1,2, Fang‑Fang Yin1,2


Downregulation of Death‑associated Protein Kinase 3 and Caspase‑3 Correlate to the Progression and Poor Prognosis of Gliomas

Ye Song, Tianshi Que, Hao Long, Xi’an Zhang, Luxiong Fang, Zhiyong Li, Songtao Qi


Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis

Ana Paula Cleto Marolla1, Jaques Waisberg2, Gabriela Tognini Saba2, Demétrius Eduardo Germini2, Maria Aparecida da Silva Pinhal1


Melanoma Antigen Gene Family in the Cancer Immunotherapy

Fengyu Zhu1, Yu Liang1, Demeng Chen2, Yang Li1


Combined Chronic Lymphocytic Leukemia and Pancreatic Neuroendocrine Carcinoma: A Collision Tumor Variation

Kaijun Huang1, Panagiotis J. Vlachostergios1, Wanhua Yang2, Rajeev L. Balmiki3


Antiproliferative and Apoptotic Effect of Pleurotus ostreatus on Human Mammary Carcinoma Cell Line (Michigan Cancer Foundation‑7)

Krishnamoorthy Deepalakshmi, Sankaran Mirunalini


Impact of Age on the Biochemical Failure and Androgen Suppression after Radical Prostatectomy for Prostate Cancer in Chilean Men

Nigel P. Murray1,2, Eduardo Reyes1,3, Nelson Orellana1, Cynthia Fuentealba1, Omar Jacob1


Carcinoma of Unknown Primary: 35 Years of a Single Institution’s Experience

Rana I. Mahmood1,2, Mohammed Aldehaim1,3, Fazal Hussain4, Tusneem A. Elhassan4,
Zubeir A. Khan5, Muhammad A. Memon6


Metformin in Ovarian Cancer Therapy: A Discussion

Yeling Ouyang1, Xi Chen2, Chunyun Zhang1, Vichitra Bunyamanop1, Jianfeng Guo3


The Progress in Molecular Biomarkers of Gliomas

Jing Qi1, Hongwei Yang2, Xin Wang2, Yanyang Tu1


Correlation between Paclitaxel Tc > 0.05 and its Therapeutic Efficacy and Severe Toxicities in Ovarian Cancer Patients

Shuyao Zhang1*, Muyin Sun2*, Yun Yuan3*, Miaojun Wang4*, Yuqi She1*, Li Zhou5, Congzhu Li5, Chen Chen1, Shengqi Zhang4


Identifying Gaps and Relative Opportunities for Discovering Membrane Proteomic Biomarkers of Triple‑negative Breast Cancer as a Translational Priority

Bhooma Venkatraman


The Molecular Mechanism and Regulatory Pathways of Cancer Stem Cells

Zhen Wang1, Hongwei Yang2, Xin Wang2, Liang Wang3, Yingduan Cheng4, Yongsheng Zhang5, Yanyang Tu1,2


Nanoparticle Drug Delivery Systems and Three‑dimensional Cell Cultures in Cancer Treatments and Research

Wenjin Shi1, Ding Weng2,3, Wanting Niu2,3


Choline Kinase Inhibitors Synergize with TRAIL in the Treatment of Colorectal Tumors and Overcomes TRAIL Resistance

Juan Carlos Lacal1, Ladislav Andera2


MicroRNA Regulating Metabolic Reprogramming in Tumor Cells: New Tumor Markers

Daniel Otero‑Albiol, Blanca Felipe‑Abrio


Biomarkers of Colorectal Cancer: A Genome‑wide Perspective

José M. Santos‑Pereira1, Sandra Muñoz‑Galván2


Nicotinamide Adenine Dinucleotide+ Metabolism Biomarkers in Malignant Gliomas

Manuel P. Jiménez‑García, Eva M. Verdugo‑Sivianes, Antonio Lucena‑Cacace


Patient-derived Xenografts as Models for Personalized Medicine Research in Cancer

Marco Perez, Lola Navas, Amancio Carnero


Genome‑wide Transcriptome Analysis of Prostate Cancer Tissue Identified Overexpression of Specific Members of the Human Endogenous Retrovirus‑K Family

Behnam Sayanjali1,2


Clinical Utility of Interleukin‑18 in Breast Cancer Patients: A Pilot Study

Reecha A. Parikh, Toral P. Kobawala, Trupti I. Trivedi, Mahnaz M. Kazi, Nandita R. Ghosh


Current and Future Systemic Treatment Options for Advanced Soft‑tissue Sarcoma beyond Anthracyclines and Ifosfamide

Nadia Hindi1,2, Javier Martin‑Broto1,2


The Genomic Organization and Function of IRX1 in Tumorigenesis and Development

Pengxing Zhang1, Hongwei Yang2, Xin Wang2, Liang Wang3, Yingduan Cheng4, Yongsheng Zhang5, Yanyang Tu1,2


Stem Cell‑based Approach in Diabetes and Pancreatic Cancer Management

Yi‑Zhou Jiang1, Demeng Chen2


Mutation Detection with a Liquid Biopsy 96 Mutation Assay in Cancer Patients and Healthy Donors

Aaron Yun Chen, Glenn D. Braunstein, Megan S. Anselmo, Jair A. Jaboni, Fernando Troy Viloria, Julie A. Neidich, Xiang Li, Anja Kammesheidt


The Application of Estrogen Receptor‑1 Mutations’ Detection through Circulating Tumor DNA in Breast Cancer

Binliang Liu, Yalan Yang, Zongbi Yi, Xiuwen Guan, Fei Ma


Circulating MicroRNAs and Long Noncoding RNAs: Liquid Biomarkers in Thoracic Cancers

Pablo Reclusa1, Anna Valentino1, Rafael Sirera1,2, Martin Frederik Dietrich3, Luis Estuardo Raez3, Christian Rolfo1


Exosomes Biology: Function and Clinical Implications in Lung Cancer

Martin Frederik Dietrich1, Christian Rolfo2, Pablo Reclusa2, Marco Giallombardo2, Anna Valentino2, Luis E. Raez1


Circulating Tumor DNA: A Potential Biomarker from Solid Tumors’ Monitor to Anticancer Therapies

Ting Chen1,2, Rongzhang He1,3, Xinglin Hu1,3,4, Weihao Luo1, Zheng Hu1,3, Jia Li1, Lili Duan1, Yali Xie1,2, Wenna Luo1,2, Tan Tan1,2, Di‑Xian Luo1,2


Novel Molecular Multilevel Targeted Antitumor Agents

Poonam Sonawane1, Young A. Choi1, Hetal Pandya2, Denise M. Herpai1, Izabela Fokt3,
Waldemar Priebe3, Waldemar Debinski1


Fish Oil and Prostate Cancer: Effects and Clinical Relevance

Pei Liang, Michael Gao Jr.


Stemness‑related Markers in Cancer

Wenxiu Zhao1, Yvonne Li2, Xun Zhang1


Autophagy Regulated by miRNAs in Colorectal Cancer Progression and Resistance

Andrew Fesler1, Hua Liu1, Ning Wu1,2, Fei Liu3, Peixue Ling3, Jingfang Ju1,3


Gastric Metastases Mimicking Primary Gastric Cancer: A Brief Literature Review

Simona Gurzu1,2,3, Marius Alexandru Beleaua1, Laura Banias2, Ioan Jung1


Possibility of Specific Expression of the Protein Toxins at the Tumor Site with Tumor‑specialized Promoter

Liyuan Zhou1,2, Yujun Li1,2, Changchen Hu3, Binquan Wang1,2


SKI‑178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models

Jeremy A. Hengst1,2, Taryn E. Dick1,2, Arati Sharma1, Kenichiro Doi3, Shailaja Hegde4, Su‑Fern Tan5, Laura M. Geffert1,2, Todd E. Fox5, Arun K. Sharma1, Dhimant Desai1, Shantu Amin1, Mark Kester5, Thomas P. Loughran5, Robert F. Paulson4, David F. Claxton6, Hong‑Gang Wang3, Jong K. Yun1,2


A T‑cell Engager‑armed Oncolytic Vaccinia Virus to Target the Tumor Stroma

Feng Yu1, Bangxing Hong1, Xiao‑Tong Song1,2,3


Real‑world Experience with Abiraterone in Metastatic Castration‑resistant Prostate Cancer

Yasar Ahmed1, Nemer Osman1, Rizwan Sheikh2, Sarah Picardo1, Geoffrey Watson1


Combination of Interleukin‑11Rα Chimeric Antigen Receptor T‑cells and Programmed Death‑1 Blockade as an Approach to Targeting Osteosarcoma Cells In vitro

Hatel Rana Moonat, Gangxiong Huang, Pooja Dhupkar, Keri Schadler, Nancy Gordon,
Eugenie Kleinerman


Efficacy and Safety of Paclitaxel‑based Therapy and Nonpaclitaxel‑based Therapy in Advanced Gastric Cancer

Tongwei Wu, Xiao Yang, Min An, Wenqin Luo, Danxian Cai, Xiaolong Qi


Motion Estimation of the Liver Based on Deformable Image Registration: A Comparison Between Four‑Dimensional‑Computed Tomography and Four‑Dimensional-Magnetic Resonance Imaging

Xiao Liang1, Fang‑Fang Yin1,2, Yilin Liu1, Brian Czito2, Manisha Palta2, Mustafa Bashir3, Jing Cai1,2


A Feasibility Study of Applying Thermal Imaging to Assist Quality Assurance of High‑Dose Rate Brachytherapy

Xiaofeng Zhu1, Yu Lei1, Dandan Zheng1, Sicong Li1, Vivek Verma1, Mutian Zhang1, Qinghui Zhang1, Xiaoli Tang2, Jun Lian2, Sha X. Chang2, Haijun Song3, Sumin Zhou1, Charles A. Enke1


Role of Exosome microRNA in Breast Cancer

Wang Qu, Ma Fei, Binghe Xu


Recent Progress in Technological Improvement and Biomedical Applications of the Clustered Regularly Interspaced Short Palindromic Repeats/Cas System

Yanlan Li1,2*, Zheng Hu1*, Yufang Yin3, Rongzhang He1, Jian Hu1, Weihao Luo1, Jia Li1, Gebo Wen2, Li Xiao1, Kai Li1, Duanfang Liao4, Di-Xian Luo1,5


The Significance of Nuclear Factor‑Kappa B Signaling Pathway in Glioma: A Review

Xiaoshan Xu1, Hongwei Yang2, Xin Wang2, Yanyang Tu1


Markerless Four‑Dimensional‑Cone Beam Computed Tomography Projection‑Phase Sorting Using Prior Knowledge and Patient Motion Modeling: A Feasibility Study

Lei Zhang1,2, Yawei Zhang2, You Zhang1,2,3, Wendy B. Harris1,2, Fang‑Fang Yin1,2,4, Jing Cai1,4,5, Lei Ren1,2


The Producing Capabilities of Interferon‑g and Interleukin‑10 of Spleen Cells in Primary and Metastasized Oral Squamous Cell Carcinoma Cells-implanted Mice

Yasuka Azuma1,2, Masako Mizuno‑Kamiya3, Eiji Takayama1, Harumi Kawaki1, Toshihiro Inagaki4, Eiichi Chihara2, Yasunori Muramatsu5, Nobuo Kondoh1


“Eating” Cancer Cells by Blocking CD47 Signaling: Cancer Therapy by Targeting the Innate Immune Checkpoint

Yi‑Rong Xiang, Li Liu


Glycosylation is Involved in Malignant Properties of Cancer Cells

Kazunori Hamamura1, Koichi Furukawa2


Biomarkers in Molecular Epidemiology Study of Oral Squamous Cell Carcinoma in the Era of Precision Medicine

Qing‑Hao Zhu1*, Qing‑Chao Shang1*, Zhi‑Hao Hu1*, Yuan Liu2, Bo Li1, Bo Wang1, An‑Hui Wang1


I‑Kappa‑B Kinase‑epsilon Activates Nuclear Factor‑kappa B and STAT5B and Supports Glioblastoma Growth but Amlexanox Shows Little Therapeutic Potential in These Tumors

Nadège Dubois1, Sharon Berendsen2, Aurélie Henry1,2, Minh Nguyen1, Vincent Bours1,
Pierre Alain Robe1,2


Suppressive Effect of Mesenchymal Stromal Cells on Interferon‑g‑Producing Capability of Spleen Cells was Specifically Enhanced through Humoral Mediator(s) from Mouse Oral Squamous Cell Carcinoma Sq‑1979 Cells In Vitro

Toshihiro Inagaki1,2, Masako Mizuno‑Kamiya3, Eiji Takayama1, Harumi Kawaki1, Eiichi Chihara4, Yasunori Muramatsu5, Shinichiro Sumitomo5, Nobuo Kondoh1


An Interplay Between MicroRNA and SOX4 in the Regulation of Epithelial–Mesenchymal Transition and Cancer Progression

Anjali Geethadevi1, Ansul Sharma2, Manish Kumar Sharma3, Deepak Parashar1


MicroRNAs Differentially Expressed in Prostate Cancer of African‑American and European‑American Men

Ernest K. Amankwah


The Role of Reactive Oxygen Species in Screening Anticancer Agents

Xiaohui Xu1, Zilong Dang2, Taoli Sun3, Shengping Zhang1, Hongyan Zhang1


Panobinostat and Its Combination with 3‑Deazaneplanocin‑A Induce Apoptosis and Inhibit In vitro Tumorigenesis and Metastasis in GOS‑3 Glioblastoma Cell Lines

Javier de la Rosa*, Alejandro Urdiciain*, Juan Jesús Aznar‑Morales, Bárbara Meléndez1,
Juan A. Rey2, Miguel A. Idoate3, Javier S. Castresana


Cancer Stem‑Like Cells Have Cisplatin Resistance and miR‑93 Regulate p21 Expression in Breast Cancer

Akiko Sasaki1, Yuko Tsunoda2, Kanji Furuya3, Hideto Oyamada1, Mayumi Tsuji1, Yuko Udaka1, Masahiro Hosonuma1, Haruna Shirako1, Nana Ichimura1, Yuji Kiuchi1


The Contribution of Hexokinase 2 in Glioma

Hui Liu1, Hongwei Yang2, Xin Wang3, Yanyang Tu1


The Mechanism of BMI1 in Regulating Cancer Stemness Maintenance, Metastasis, Chemo‑ and Radiation Resistance

Xiaoshan Xu, Zhen Wang, Nan Liu, Pengxing Zhang, Hui Liu, Jing Qi, Yanyang Tu


A Multisource Adaptive Magnetic Resonance Image Fusion Technique for Versatile Contrast Magnetic Resonance Imaging

Lei Zhang1,2, Fang‑Fang Yin1,2,3, Brittany Moore1,2, Silu Han1,2, Jing Cai1,2,4


Senescence and Cancer

Sulin Zeng1,2, Wen H. Shen2, Li Liu1


The “Wild”‑type Gastrointestinal Stromal Tumors: Heterogeneity on Molecule Characteristics and Clinical Features

Yanhua Mou1, Quan Wang1, Bin Li1,2


Retreatment with Cabazitaxel in a Long‑Surviving Patient with Castration‑Resistant Prostate Cancer and Visceral Metastasis

Raquel Luque Caro, Carmen Sánchez Toro, Lucia Ochoa Vallejo


Therapy‑Induced Histopathological Changes in Breast Cancers: The Changing Role of Pathology in Breast Cancer Diagnosis and Treatment

Shazima Sheereen1, Flora D. Lobo1, Waseemoddin Patel2, Shamama Sheereen3,
Abhishek Singh Nayyar4, Mubeen Khan5


Glioma Research in the Era of Medical Big Data

Feiyifan Wang1, Christopher J. Pirozzi2, Xuejun Li1


Transarterial Embolization for Hepatocellular Adenomas: Case Report and Literature Review

Jian‑Hong Zhong1,2, Kang Chen1, Bhavesh K. Ahir3, Qi Huang4, Ye Wu4, Cheng‑Cheng Liao1, Rong‑Rong Jia1, Bang‑De Xiang1,2, Le‑Qun Li1,2


Nicotinamide Phosphoribosyltransferase: Biology, Role in Cancer, and Novel Drug Target

Antonio Lucena‑Cacace1,2,3, Amancio Carnero1,2


Enhanced Anticancer Effect by Combination of Proteoglucan and Vitamin K3 on Bladder Cancer Cells

Michael Zhang, Kelvin Zheng, Muhammad Choudhury, John Phillips, Sensuke Konno


Molecular Insights Turning Game for Management of Ependymoma: A Review of Literature

Ajay Sasidharan, Rahul Krishnatry


IDH Gene Mutation in Glioma

Leping Liu1, Xuejun Li1,2


Challenges and Advances in the Management of Pediatric Intracranial Germ Cell Tumors: A Case Report and Literature Review

Gerard Cathal Millen1, Karen A. Manias1,2, Andrew C. Peet1,2, Jenny K. Adamski1


Assessing the Feasibility of Using Deformable Registration for Onboard Multimodality‑Based Target Localization in Radiation Therapy

Ge Ren1,2,3, Yawei Zhang1,2, Lei Ren1,2


Research Advancement in the Tumor Biomarker of Hepatocellular Carcinoma

Qing Du1, Xiaoying Ji2, Guangjing Yin3, Dengxian Wei3, Pengcheng Lin1, Yongchang Lu1,
Yugui Li3, Qiaohong Yang4, Shizhu Liu5, Jinliang Ku5, Wenbin Guan6, Yuanzhi Lu7


Novel Insights into the Role of Bacterial Gut Microbiota in Hepatocellular Carcinoma

Lei Zhang1, Guoyu Qiu2, Xiaohui Xu2, Yufeng Zhou3, Ruiming Chang4


Central Odontogenic Fibroma with Unusual Presenting Symptoms

Aanchal Tandon, Bharadwaj Bordoloi, Safia Siddiqui, Rohit Jaiswal


The Prognostic Role of Lactate in Patients Who Achieved Return of Spontaneous Circulation after Cardiac Arrest: A Systematic Review and Meta‑analysis

Dongni Ren1, Xin Wang2, Yanyang Tu1,2


Inhibitory Effect of Hyaluronidase‑4 in a Rat Spinal Cord Hemisection Model

Xipeng Wang1,2, Mitsuteru Yokoyama2, Ping Liu3


Research and Development of Anticancer Agents under the Guidance of Biomarkers

Xiaohui Xu1, Guoyu Qiu1, Lupeng Ji2, Ruiping Ma3, Zilong Dang4, Ruling Jia1, Bo Zhao1


Idiopathic Hypereosinophilic Syndrome and Disseminated Intravascular Coagulation

Mansoor C. Abdulla


Phosphorylation of BRCA1‑Associated Protein 1 as an Important Mechanism in the Evasion of Tumorigenesis: A Perspective

Guru Prasad Sharma1, Anjali Geethadevi2, Jyotsna Mishra3, G. Anupa4, Kapilesh Jadhav5,
K. S. Vikramdeo6, Deepak Parashar2


Progress in Diagnosis and Treatment of Mixed Adenoneuroendocrine Carcinoma of Biliary‑Pancreatic System

Ge Zengzheng1, Huang-Sheng Ling2, Ming-Feng Li2, Xu Xiaoyan1, Yao Kai1, Xu Tongzhen3,
Ge Zengyu4, Li Zhou5


Surface-Enhanced Raman Spectroscopy to Study the Biological Activity of Anticancer Agent

Guoyu Qiu1, Xiaohui Xu1, Lupeng Ji2, Ruiping Ma3, Zilong Dang4, Huan Yang5


Alzheimer’s Disease Susceptibility Genes in Malignant Breast Tumors

Steven Lehrer1, Peter H. Rheinstein2


OSMCC: An Online Survival Analysis Tool for Merkel Cell Carcinoma

Umair Ali Khan Saddozai1, Qiang Wang1, Xiaoxiao Sun1, Yifang Dang1, JiaJia Lv1,2, Junfang Xin1, Wan Zhu3, Yongqiang Li1, Xinying Ji1, Xiangqian Guo1


Protective Activity of Selenium against 5‑Fluorouracil‑Induced Nephrotoxicity in Rats

Elias Adikwu, Nelson Clemente Ebinyo, Beauty Tokoni Amgbare


Advances on the Components of Fibrinolytic System in Malignant Tumors

Zengzheng Ge1, Xiaoyan Xu1, Zengyu Ge2, Shaopeng Zhou3, Xiulin Li1, Kai Yao1, Lan Deng4


A Patient with Persistent Foot Swelling after Ankle Sprain: B‑Cell Lymphoblastic Lymphoma Mimicking Soft‑tissue Sarcoma

Crystal R. Montgomery‑Goecker1, Andrew A. Martin2, Charles F. Timmons3, Dinesh Rakheja3, Veena Rajaram3, Hung S. Luu3


Coenzyme Q10 and Resveratrol Abrogate Paclitaxel‑Induced Hepatotoxicity in Rats

Elias Adikwu, Nelson Clemente Ebinyo, Loritta Wasini Harris


Progress in Clinical Follow‑up Study of Dendritic Cells Combined with Cytokine‑Induced Killer for Stomach Cancer

Ling Wang1,2, Run Wan1,2, Cong Chen1,2, Ruiliang Su1,2, Yumin Li1,2


Supraclavicular Lymphadenopathy as the Initial Manifestation in Carcinoma of Cervix

Priyanka Priyaarshini1, Tapan Kumar Sahoo2


ABO Typing Error Resolution and Transfusion Support in a Case of an Acute Leukemia Patient Showing Loss of Antigen Expression

Debasish Mishra1, Gopal Krushna Ray1, Smita Mahapatra2, Pankaj Parida2


Protein Disulfide Isomerase A3: A Potential Regulatory Factor of Colon Epithelial Cells

Yang Li1, Zhenfan Huang2, Haiping Jiang3


Clinicopathological Association of p16 and its Impact on Outcome of Chemoradiation in Head‑and‑Neck Squamous Cell Cancer Patients in North‑East India

Srigopal Mohanty1, Yumkhaibam Sobita Devi2, Nithin Raj Daniel3, Dulasi Raman Ponna4,
Ph. Madhubala Devi5, Laishram Jaichand Singh2


Potential Inhibitor for 2019‑Novel Coronaviruses in Drug Development

Xiaohui Xu1, Zilong Dang2, Lei Zhang3, Lingxue Zhuang4, Wutang Jing5, Lupeng Ji6, Guoyu Qiu1


Best‑Match Blood Transfusion in Pediatric Patients with Mixed Autoantibodies

Debasish Mishra1, Dibyajyoti Sahoo1, Smita Mahapatra2, Ashutosh Panigrahi3


Characteristics and Outcome of Patients with Pheochromocytoma

Nadeema Rafiq1, Tauseef Nabi2, Sajad Ahmad Dar3, Shahnawaz Rasool4


Comparison of Histopathological Grading and Staging of Breast Cancer with p53‑Positive and Transforming Growth Factor‑Beta Receptor 2‑Negative Immunohistochemical Marker Expression Cases

Palash Kumar Mandal1, Anindya Adhikari2, Subir Biswas3, Amita Giri4, Arnab Gupta5,
Arindam Bhattacharya6


Chemical Compositions and Antiproliferative Effect of Essential Oil of Asafoetida on MCF7 Human Breast Cancer Cell Line and Female Wistar Rats

Seyyed Majid Bagheri1,2, Davood Javidmehr3, Mohammad Ghaffari1, Ehsan Ghoderti‑Shatori4


Cyclooxygenase‑2 Contributes to Mutant Epidermal Growth Factor Receptor Lung Tumorigenesis by Promoting an Immunosuppressive Environment

Mun Kyoung Kim1, Aidin Iravani2, Matthew K. Topham2,3


Potential role of CircMET as A Novel Diagnostic Biomarker of Papillary Thyroid Cancer

Yan Liu1,2,3,4#, Chen Cui1,2,3,4#, Jidong Liu1,2,3,4, Peng Lin1,2,3,4,Kai Liang1,2,3,4, Peng Su5, Xinguo Hou1,2,3,4, Chuan Wang1,2,3,4, Jinbo Liu1,2,3,4, Bo Chen6, Hong Lai1,2,3,4, Yujing Sun1,2,3,4* and Li Chen 1,2,3,4*


Cuproptosis-related Genes in Glioblastoma as Potential Therapeutic Targets

Zhiyu Xia1,2, Haotian Tian1, Lei Shu1,2, Guozhang Tang3, Zhenyu Han4, Yangchun Hu1*, Xingliang Dai1*


Cancer Diagnosis and Treatments by Porous Inorganic Nanocarriers

Jianfeng Xu1,2, Hanwen Zhang1,2, Xiaohui Song1,2, Yangong Zheng3, Qingning Li1,2,4*


Delayed (20 Years) post-surgical Esophageal Metastasis of Breast Cancer - A Case Report

Bowen Hu1#, Lingyu Du2#, Hongya Xie1, Jun Ma1, Yong Yang1*, Jie Tan2*


Subtyping of Undifferentiated Pleomorphic Sarcoma and Its Clinical Meaning

Umair Ali Khan Saddozai, Zhendong Lu, Fengling Wang, Muhammad Usman Akbar, Saadullah Khattak, Muhammad Badar, Nazeer Hussain Khan, Longxiang Xie, Yongqiang Li, Xinying Ji, Xiangqian Guo


Construction of Glioma Prognosis Model and Exploration of Related Regulatory Mechanism of Model Gene

Suxia Hu, Abdusemer Reyimu, Wubi Zhou, Xiang Wang, Ying Zheng, Xia Chen, Weiqiang Li, Jingjing Dai


ESRP2 as a Non-independent Potential Biomarker-Current Progress in Tumors

Yuting Chen, Yuzhen Rao, Zhiyu Zeng, Jiajie Luo, Chengkuan Zhao, Shuyao Zhang


Resection of Bladder Tumors at the Ureteral Orifice Using a Hook Plasma Electrode: A Case Report

Jun Li, Ziyong Wang, Qilin Wang


Structural Characterization and Bioactivity for Lycium Barbarum Polysaccharides

Jinghua Qi1,2,  Hangping Chen3,Huaqing Lin2,4,Hongyuan Chen1,2,5* and Wen Rui2,3,5,6*


The Role of IL-22 in the Prevention of Inflammatory Bowel Disease and Liver Injury

Xingli Qi1,2, Huaqing Lin2,3, Wen Rui2,3,4,5 and Hongyuan Chen1,2,3


RBM15 and YTHDF3 as Positive Prognostic Predictors in ESCC: A Bioinformatic Analysis Based on The Cancer Genome Atlas (TCGA)

Yulou Luo1, Lan Chen2, Ximing Qu3, Na Yi3, Jihua Ran4, Yan Chen3,5*


Mining and Analysis of Adverse Drug Reaction Signals Induced by Anaplastic Lymphoma Kinase-Tyrosine Kinase Inhibitors Based on the FAERS Database

Xiumin Zhang1,2#, Xinyue Lin1,3#, Siman Su1,3#, Wei He3, Yuying Huang4, Chengkuan Zhao3, Xiaoshan Chen3, Jialin Zhong3, Chong Liu3, Wang Chen3, Chengcheng Xu3, Ping Yang5, Man Zhang5, Yanli Lei5*, Shuyao Zhang1,3*


Advancements in Immunotherapy for Advanced Gastric Cancer

Min Jiang1#, Rui Zheng1#, Ling Shao1, Ning Yao2, Zhengmao Lu1*


Tumor Regression after COVID-19 Infection in Metastatic Adrenocortical Carcinoma Treated with Immune Checkpoint Blockade: A Case Report

Qiaoxin Lin1, Bin Liang1, Yangyang Li2, Ling Tian3*, Dianna Gu1*


Mining and Analysis of Adverse Events of BRAF Inhibitors Based on FDA Reporting System

Silan Peng1,2#, Danling Zheng1,3#, Yanli Lei4#, Wang Chen3, Chengkuan Zhao3, Xinyue Lin1, Xiaoshan Chen3, Wei He3, Li Li3, Qiuzhen Zhang5*, Shuyao Zhang1,3*


Malignant Phyllodes Tumor with Fever, Anemia, Hypoproteinemia: A Rare and Strange Case Report and Literature Review

Zhenghang Li1, Yuxian Wei1*


Construction of Cuproptosis-Related LncRNA Signature as a Prognostic Model Associated with Immune Microenvironment for Clear-Cell Renal Cell Carcinoma

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