Pharmacogenetics: Role in Cancer treatment

Pharmacogenetics is the study of how the genes in an individual are likely to influence the response towards a drug.

The need for Pharmacogenetics:

Pharmacogenetics helps to classify patients as those that are likely to respond, those that are unlikely to respond and those that are likely to experience or unlikely to experience toxicity following administration of a drug.

Relation between Pharmacogenetics and Cancer:

Cancer usually results from gene polymorphisms that cause minor/major changes in the DNA sequences. These changes can be substitutions, deletions, insertions, repeats, gene copy number variations and in certain cases, rearrangements. Pharmacogenetics helps in identifying the relation between gene polymorphisms and drug response, in terms of efficacy, adverse effects and toxicity. This would help in the prescription of drugs having maximum efficacy and at the same time, reduced toxicity and improve health care. It can help to underline patient care in coming future of precision medicine.

Biomarkers in Pharmacogenetics:

Biomarkers are molecules such as DNA (genes), proteins or hormones which can be used as an indicator of an underlying disease or condition.

Biomarkers can be classified into 2 types –

1. Prognostics biomarkers which provide information on the likely course of cancer, including the aggressiveness of the disease, regardless of treatment.
2. Predictive biomarkers which can be used to identify patients which are likely to or unlikely to benefit from a particular treatment.

Examples of predictive biomarkers:

1. 5-Fluorouracil (5-FU) is a chemotherapeutic agent used in various cancer types such as colon, rectal and gastric cancers. Dihydropyrimidine dehydrogenase (DPYD) is the enzyme which is responsible for the metabolism of 5-FU to the inactive 5,6- dihydrofluorouracil. Genetic variants in the DPYD gene would likely confer deficient DPYD enzyme activity in patients, thus increasing the risk of 5-FU induced toxicity.
2. Activating mutations in the EGFR gene results in constitutive signaling via the PI3K-AKT and MAPK pathways. Deletions in exon 19 and a missense mutation in exon 21 are considered a positive predictive biomarker for small molecule TKIs (Tyrosine Kinase Inhibitors) such as erlotinib, gefitinib and afatinib which target the EGFR gene.

Benefits of Pharmacogenetic testing:

1. To a certain extent, it would help in predicting the risk from cancer for a given individual. This would include screening for biomarkers playing a role in the initiation of cancer, its aggressiveness and spreading to various body parts.
2. It can also help the clinicians to decide and come up with better treatment regimens having minimum toxicity.

References:

Padh, Harish. “Pharmacogenetics and cancer management.” (2018).

Patel, Jai N. “Cancer pharmacogenomics, challenges in implementation, and patient-focused perspectives.”Pharmacogenomics and personalized medicine 9 (2016): 65.

Robert, Jacques, et al. “On the use of pharmacogenetics in cancer treatment and clinical trials.”European journal of cancer 50.15 (2014): 2532-2543.

–By Royden Lobo