PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies
Abstract With the widespread use of PD‐1/PD‐L1 monoclonal antibodies (mAbs) in the treatment of multiple malignant tumors, they were also gradually applied to advanced renal cell carcinoma (aRCC). Nowadays, multiple PD‐1/PD‐L1 mAbs, such as nivolumab, avelumab, and pembrolizumab, have achieved consi...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2021-09-01
|
Series: | Cancer Medicine |
Subjects: | |
Online Access: | https://doi.org/10.1002/cam4.4190 |
id |
doaj-9eaeaf7fb09744d79cba180282df563a |
---|---|
record_format |
Article |
spelling |
doaj-9eaeaf7fb09744d79cba180282df563a2021-09-17T05:24:01ZengWileyCancer Medicine2045-76342021-09-0110186384640110.1002/cam4.4190PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapiesLei Ding0Hui yu Dong1Tian ren Zhou2Yu hao Wang3Tao Yan4Jun chen Li5Zhong yuan Wang6Jie Li7Chao Liang8Department of Urology The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Urology The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Urology The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Urology The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Urology The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Urology The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Urology The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Urology The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Urology The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaAbstract With the widespread use of PD‐1/PD‐L1 monoclonal antibodies (mAbs) in the treatment of multiple malignant tumors, they were also gradually applied to advanced renal cell carcinoma (aRCC). Nowadays, multiple PD‐1/PD‐L1 mAbs, such as nivolumab, avelumab, and pembrolizumab, have achieved considerable efficacy in clinical trials. However, due to the primary, adaptive, and acquired resistance to these mAbs, the efficacy of this immunotherapy is not satisfactory. Theories also vary as to why the difference in efficacy occurs. The alterations of PD‐L1 expression and the interference of cellular immunity may affect the efficacy. These mechanisms demand to be revealed to achieve a sustained and complete objective response in patients with aRCC. Tyrosine kinase inhibitors have been proven to have synergistic mechanisms with PD‐1/PD‐L1 mAb in the treatment of aRCC, and CTLA‐4 mAb has been shown to have a non‐redundant effect with PD‐1/PD‐L1 mAb to enhance efficacy. Although combinations with targeted agents or other checkpoint mAbs have yielded enhanced clinical outcomes in multiple clinical trials nowadays, the potential of PD‐1/PD‐L1 mAbs still has a large development space. More potential mechanisms that affect the efficacy demand to be developed and transformed into the clinical treatment of aRCC to search for possible combination regimens. We elucidate these mechanisms in RCC and present existing combination therapies applied in clinical trials. This may help physicians’ select treatment options for patients with refractory kidney cancer.https://doi.org/10.1002/cam4.4190advanced renal cell carcinomacellular immunitycombination therapyfundamental mechanismsPD‐1PD‐L1 inhibitor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lei Ding Hui yu Dong Tian ren Zhou Yu hao Wang Tao Yan Jun chen Li Zhong yuan Wang Jie Li Chao Liang |
spellingShingle |
Lei Ding Hui yu Dong Tian ren Zhou Yu hao Wang Tao Yan Jun chen Li Zhong yuan Wang Jie Li Chao Liang PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies Cancer Medicine advanced renal cell carcinoma cellular immunity combination therapy fundamental mechanisms PD‐1 PD‐L1 inhibitor |
author_facet |
Lei Ding Hui yu Dong Tian ren Zhou Yu hao Wang Tao Yan Jun chen Li Zhong yuan Wang Jie Li Chao Liang |
author_sort |
Lei Ding |
title |
PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies |
title_short |
PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies |
title_full |
PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies |
title_fullStr |
PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies |
title_full_unstemmed |
PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies |
title_sort |
pd‐1/pd‐l1 inhibitors‐based treatment for advanced renal cell carcinoma: mechanisms affecting efficacy and combination therapies |
publisher |
Wiley |
series |
Cancer Medicine |
issn |
2045-7634 |
publishDate |
2021-09-01 |
description |
Abstract With the widespread use of PD‐1/PD‐L1 monoclonal antibodies (mAbs) in the treatment of multiple malignant tumors, they were also gradually applied to advanced renal cell carcinoma (aRCC). Nowadays, multiple PD‐1/PD‐L1 mAbs, such as nivolumab, avelumab, and pembrolizumab, have achieved considerable efficacy in clinical trials. However, due to the primary, adaptive, and acquired resistance to these mAbs, the efficacy of this immunotherapy is not satisfactory. Theories also vary as to why the difference in efficacy occurs. The alterations of PD‐L1 expression and the interference of cellular immunity may affect the efficacy. These mechanisms demand to be revealed to achieve a sustained and complete objective response in patients with aRCC. Tyrosine kinase inhibitors have been proven to have synergistic mechanisms with PD‐1/PD‐L1 mAb in the treatment of aRCC, and CTLA‐4 mAb has been shown to have a non‐redundant effect with PD‐1/PD‐L1 mAb to enhance efficacy. Although combinations with targeted agents or other checkpoint mAbs have yielded enhanced clinical outcomes in multiple clinical trials nowadays, the potential of PD‐1/PD‐L1 mAbs still has a large development space. More potential mechanisms that affect the efficacy demand to be developed and transformed into the clinical treatment of aRCC to search for possible combination regimens. We elucidate these mechanisms in RCC and present existing combination therapies applied in clinical trials. This may help physicians’ select treatment options for patients with refractory kidney cancer. |
topic |
advanced renal cell carcinoma cellular immunity combination therapy fundamental mechanisms PD‐1 PD‐L1 inhibitor |
url |
https://doi.org/10.1002/cam4.4190 |
work_keys_str_mv |
AT leiding pd1pdl1inhibitorsbasedtreatmentforadvancedrenalcellcarcinomamechanismsaffectingefficacyandcombinationtherapies AT huiyudong pd1pdl1inhibitorsbasedtreatmentforadvancedrenalcellcarcinomamechanismsaffectingefficacyandcombinationtherapies AT tianrenzhou pd1pdl1inhibitorsbasedtreatmentforadvancedrenalcellcarcinomamechanismsaffectingefficacyandcombinationtherapies AT yuhaowang pd1pdl1inhibitorsbasedtreatmentforadvancedrenalcellcarcinomamechanismsaffectingefficacyandcombinationtherapies AT taoyan pd1pdl1inhibitorsbasedtreatmentforadvancedrenalcellcarcinomamechanismsaffectingefficacyandcombinationtherapies AT junchenli pd1pdl1inhibitorsbasedtreatmentforadvancedrenalcellcarcinomamechanismsaffectingefficacyandcombinationtherapies AT zhongyuanwang pd1pdl1inhibitorsbasedtreatmentforadvancedrenalcellcarcinomamechanismsaffectingefficacyandcombinationtherapies AT jieli pd1pdl1inhibitorsbasedtreatmentforadvancedrenalcellcarcinomamechanismsaffectingefficacyandcombinationtherapies AT chaoliang pd1pdl1inhibitorsbasedtreatmentforadvancedrenalcellcarcinomamechanismsaffectingefficacyandcombinationtherapies |
_version_ |
1717377583349235712 |