Pharmacogenetics of anticancer monoclonal antibodies

Dmitrii Shek; Scott A Read; Golo Ahlenstiel; Irina Piatkov

doi:10.20517/cdr.2018.20

Pharmacogenetics of anticancer monoclonal antibodies

Cancer Drug Resist. 2019 Mar 19;2(1):69-81. doi: 10.20517/cdr.2018.20. eCollection 2019.

Authors

Dmitrii Shek¹, Scott A Read^{1

2}, Golo Ahlenstiel^{1

2

3}, Irina Piatkov³

Affiliations

¹ Blacktown Clinical School, Western Sydney University, Blacktown, NSW 2148, Australia.
² Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
³ Blacktown Hospital, Blacktown, NSW 2148, Australia.

Abstract

Pharmacogenetics is the study of therapeutic and adverse responses to drugs based on an individual's genetic background. Monoclonal antibodies (mAbs) are a rapidly evolving field in cancer therapy, however a number of newly developed and highly effective mAbs (e.g., anti-CTLA-4 and anti-PD-1) possess pharmacogenomic profiles that remain largely undefined. Since the first chemotherapeutic mAb Rituximab was approved in 1997 by the US Food and Drug Administration for cancer treatment, a broad number of other mAbs have been successfully developed and implemented into oncological practice. Nowadays, mAbs are considered as one of the most promising new approaches for cancer treatment. The efficacy of mAb treatment can however be significantly affected by genetic background, where genes responsible for antibody presentation and metabolism, for example, can seriously affect patient outcome. This review will focus on current anticancer mAb treatments, patient genetics that shape their efficacy, and the molecular pathways that bridge the two.

Keywords: Pharmacogenetics; cancer immunotherapy; immune-checkpoint proteins; monoclonal antibodies; personalized medicine; pharmacogenomics.

Publication types

Review