Targeting the Programmed Cell Death-1 Pathway in Genitourinary Tumors: Current Progress and Future Perspectives

Current Drug Metabolism
Steven A MannLiang Cheng

Abstract

Immune checkpoint inhibitors have revolutionized the treatment of many malignancies with over a dozen new United States Food and Drug Administration (FDA) approvals in the past six years. Due to the combination of potent treatment success and potentially deadly adverse effects from immune checkpoint inhibitors, gathering prognostic and predictive information about FDA-indicated tumors is prudent. PD-L1 expression is a poor prognostic factor and predictive of better responses from both PD-1 and PD-L1 inhibitors in a variety of tumor types including Renal Cell Carcinoma (RCC) and urothelial carcinoma. Each FDAapproved PD-1/PD-L1 drug is paired with a PD-L1 Immunohistochemistry (IHC) assay. The majority of PD-1/PDL1 inhibitor clinical trials use proprietary IHC antibodies with undefined validation data. Thus, there is need for improved knowledge and application of PD-1/PD-L1 IHC biomarkers. There is a wealth of recent publications using antibody clones to characterize tumor PD-1/PD-L1 expression profiles. PD-1 is expressed on lymphocytes. PD-L1 is expressed on both tumor cells and immune cells. IHC staining appears in membranous fashion. A cutoff of at least 5% tumor cell PD-L1 staining for positivity has worked for most studies. ...Continue Reading

Citations

Sep 20, 2019·Journal for Immunotherapy of Cancer·Mouhammed Amir HabraAung Naing
Aug 3, 2019·Archives of Pathology & Laboratory Medicine·Martin J Magers, Liang Cheng
Nov 20, 2018·Frontiers in Oncology·Antonio Lopez-BeltranRodolfo Montironi
Feb 10, 2019·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Peter SchramlHolger Moch
Apr 12, 2019·Frontiers in Oncology·Alessia CimadamoreMarina Scarpelli
Nov 25, 2017·International Journal of Urology : Official Journal of the Japanese Urological Association·Teruo InamotoHaruhito Azuma
Jan 28, 2021·Biomedicines·Izabela KarwackaKrzysztof Sworczak
Mar 27, 2021·Investigational New Drugs·Andrew W HahnAung Naing

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Related Papers

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Sukhmani K PaddaHeather A Wakelee
© 2022 Meta ULC. All rights reserved