Use of pharmacogenetics for predicting cancer prognosis and treatment exposure, response and toxicity

Abstract

Cancer treatment is complicated because of a multitude of treatment options and little patient-specific information to help clinicians choose appropriate therapy. There are two genomes relevant in cancer treatment: the tumor (somatic) and the patient (germline). Together, these two genomes dictate treatment outcome through four processes: the somatic genome primarily determines tumor prognosis and response while the germline genome modulates treatment exposure and toxicity. In this review, we describe the influence of these genomes on treatment outcomes by highlighting examples of genetic variation that are predictors of each of these four factors, prognosis, response, toxicity and exposure, and discuss the translation and clinical implementation of each. Use of pre-treatment pharmacogenetic testing will someday enable clinicians to make individualized therapy decisions about aggressiveness, drug selection and dose, improving treatment outcomes for cancer patients.

Gene-Environment Interactions in Human Health

“…Somatic mutations are most commonly studied in the context of tumor cells, although they have also been observed in neurons (Poduri et al 2013) and other tissues (O'Huallachain et al 2012). Some researchers are investigating the relationship between these somatic genetic alterations and response to therapy (Hertz and McLeod 2013), a form of pharmacogenomics. Another form of genetic variation which may be investigated is epigenetic variation.…”

The genetic variants underlying breast cancer treatment-induced chronic and late toxicities: A systematic review

“…However, the sporadic and unpredictable nature of chronic and late toxicities suggests a potential role for genetics in their etiologies. A patient's germline genome plays an important role in the determination of their individual response to therapeutic agents [59,60]. Thus, the presence of germline mutations in genes that encode for drug-metabolizing enzymes, transporters, receptors and signaling pathways may result in the large disparity in individual responses to anti-cancer treatments.…”

Imatinib-induced ophthalmological side-effects in GIST patients are associated with the variations of EGFR, SLC22A1, SLC22A5 and ABCB1

“…10,11 Increasing body of evidence recognized that influx-and efflux-transporters of ABC (adenosine triphosphatebinding cassette) 12,13 and SLC (solute carrier) families with great affinity to Imatinib influence clinical responses. [14][15][16][17][18] Patients with low expression or activity of OCT1 (encoded by SLC22A1) had a lower probability of achieving a cytogenetic or molecular remission to CML.…”