Pharmacogenetics of anticancer monoclonal antibodies
Dmitrii Shek1, Scott A Read1,2, Golo Ahlenstiel1,2,3
1Blacktown Clinical School, Western Sydney University, 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.
Insights
Pharmacogenetics explores how individual genetics impact drug responses. This review examines how patient genetics influence the effectiveness of monoclonal antibodies (mAbs) in cancer therapy, focusing on current treatments and underlying molecular pathways.
Area of Science:
- Oncology
- Pharmacogenetics
- Immunotherapy
Background:
- Monoclonal antibodies (mAbs) are a significant advancement in cancer therapy, with increasing clinical use.
- Despite their efficacy, the pharmacogenomic profiles of many novel mAbs, such as anti-CTLA-4 and anti-PD-1, are not well-defined.
- The genetic background of patients can substantially influence the efficacy and outcomes of mAb treatments.
Purpose of the Study:
- To review current anticancer monoclonal antibody (mAb) treatments.
- To explore the role of patient genetics in shaping the efficacy of these mAb therapies.
- To identify and discuss the molecular pathways that connect patient genetics to mAb treatment outcomes.
Main Methods:
- Literature review of current anticancer mAb therapies.
- Analysis of studies investigating the impact of genetic variations on mAb efficacy.
- Exploration of molecular mechanisms underlying pharmacogenetic effects in mAb treatment.
Main Results:
- The efficacy of monoclonal antibody (mAb) therapy is significantly influenced by individual genetic factors.
- Specific genes involved in antibody presentation and metabolism play a crucial role in patient response.
- Undefined pharmacogenomic profiles for novel mAbs highlight a gap in personalized cancer treatment.
Conclusions:
- Understanding the pharmacogenetics of mAbs is essential for optimizing cancer therapy.
- Personalizing mAb treatment based on patient genetics can improve therapeutic outcomes.
- Further research into molecular pathways is needed to bridge genetics and mAb efficacy.
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