Cancer Drug Delivery: Pharmacogenetics, Biomarkers, and Targeted Therapies

Cancer Drug Delivery: Pharmacogenetics, Biomarkers, and Targeted Therapies

Jai N. Patel (Levine Cancer Institute, USA) and Jeryl Villadolid (Levine Cancer Institute, USA)
Copyright: © 2017 |Pages: 44
DOI: 10.4018/978-1-5225-1762-7.ch008
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Abstract

Advancements in cancer drug delivery have led to the development of personalized oncology care through molecularly-driven targeted therapies. Understanding molecular and cellular mechanisms which drive tumor progression and resistance is critical in managing new treatment strategies which have shifted from empiric to biomarker-directed therapy selection. Biomarker-directed therapies have improved clinical outcomes in multiple malignancies as monotherapy and in combination with other treatment modalities, however the changing scope of treatment options presents new opportunities and challenges for research. Furthermore, pharmacogenetics may provide a rationale method of personalizing anticancer drug dosing and supportive care management for oncology patients. This chapter reviews biomarker classifications and pharmacogenetics in anticancer therapy and supportive care. Examples of biomarker-directed therapies and clinical assays, in addition to future directions of molecular profiling in oncology therapy management are discussed.
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Introduction

Novel methods of individualizing cancer drug delivery and selection are critical to improve patient outcomes given the large heterogeneity in drug response that exists across the cancer patient population. Until recently, the majority of genomic cancer research has been in discovery and validation; however, as our knowledge of tumor molecular profiling improves, the implementation of genomic cancer medicine in the clinic becomes increasingly tangible, paralleled with the development of dozens of targeted cancer therapies (Tran et al., 2012). Our current understanding of cancer at the molecular level has resulted in a shift from characterizing tumors solely based on their anatomical location and histology to consideration of their molecular profile, opening an array of possibilities for a targeted approach to cancer therapy (Macconaill, Van Hummelen, Meyerson, & Hahn, 2011).

Pharmacogenetic biomarkers found within the tumor and the host offer valuable information for personalizing anticancer drug delivery. As the number of clinical assays available to test for pharmacogenetic biomarkers increases, it is imperative for clinicians to understand the therapeutic implications of mutations occurring within these molecular pathways to aid in drug selection and delivery. This chapter aims to summarize clinically relevant pharmacogenetic biomarkers, which may be used to personalize cancer therapy selection and dosing, in addition to a review of pharmacogenetics in supportive care management related to the treatment of cancer-related symptoms. Tables 1 and 2 summarize clinically relevant somatic and germ-line pharmacogenetic biomarkers and drug targets, and their respective clinical assays available in practice.

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