As a field, precision medicine holds great promise in the prevention and treatment of cancer. To date, oncology has the largest share of the precision medicine market, and its use is expected to grow another 12% by 2020.
A subset of precision medicine, pharmacogenomics, is also growing exponentially, especially in oncology. Currently, 165 drugs or combinations are influenced by pharmacogenetics, and 58 of those are specific to oncology/hematology.
In her article in the December 2017 issue of the Clinical Journal of Oncology Nursing, Crystal H. Dodson, PhD, RN, BC-ADM, presented an overview of pharmacogenomics and the principles that oncology nurses need to understand as the field continues to permeate many aspects of oncology nursing practice, providing hope and improved outcomes for patients with cancer.
Relevance to Oncology Nursing
Dodson explained why every oncology nurse needs to have knowledge of pharmacogenomics: in addition to predicting response to treatment, pharmacogenomics can also show which patients are likely to have an adverse drug reaction (ADR). Plus, those ADRs can be minimized or prevented altogether by basing treatment choices and dosages on a patient’s genetic profile.
Additionally, as the primary healthcare point of contact for patients with cancer, oncology nurses are in a key position to educate and guide patients and caregivers regarding precision medicine treatments.
See Figure 1 for a list of resources oncology nurses can use to learn more about pharmacogenomics.
How Genomics and Tumor Markers Affect Treatments
Genetic polymorphisms are common in humans, and many do not cause disease and in fact remain quite neutral, Dodson said. However, certain ones are implicated in cancer and the effect of certain cancer treatments.
One such genetic variation is called a single nucleotide polymorphism (SNP), the most common of which are involved in drug metabolism. For example, a SNP called CYP2D6 can affect how patients metabolize tamoxifen into endoxifen, its primary active metabolite. Determining whether patients are poor metabolizers (inhibitors), intermediate metabolizers, extensive metabolizers (normal), or ultra-rapid metabolizers can predict how effective tamoxifen therapy can be in a given individual.
Similarly, tumor markers are produced by healthy and cancerous cells, but cancer cells release a much higher level of tumor markers. Many targeted cancer therapies depend on testing for the presence of a tumor marker to determine whether the drug is appropriate; precision medicine uses DNA-based tests that uncover patterns of gene expression and changes.
Examples of these tests include the BRCA1 and BRCA2 tests, which help clinicians determine the appropriate therapy for breast or ovarian cancer, and the BCR-ABL fusion test, that confirms diagnosis and Philadelphia chromosome status as well as predicts response to therapy for various leukemias.
Types of Tumor Marker Tests
Drug disposition: A drug disposition test looks for alterations in the function of proteins involved in the disposition of a drug (i.e., absorption, metabolism, distribution, excretion) that would lead to varying concentrations of the drug in different patients. Using the CYP2D6 example from before, studies have shown that patients who are intermediate or poor metabolizers have significantly lower relapse-free survival rates after using tamoxifen for breast cancer than extensive or ultra-rapid metabolizers. In addition to a lower response to treatment, those patients may also experience more ADRs from tamoxifen because of the reduced metabolism rate.
Drug target: These tests look for genetic polymorphisms that change the activity of a drug target, thereby altering the drug response. Dodson (2017) used the example of irinotecan, whose active metabolite is inactivated by UGT1A1. Low UGT1A1 enzyme activity increases a patient’s risk for ADRs, the most common of which is neutropenia. The risk is more profound when patients have two identical UGT1A1*28 alleles, so much that the U.S. Food and Drug Administration recommends a reduced irinotecan dose in these patients.
Targeted cancer therapies: Dodson explained that this is the most common pharmacogenomics test in today’s cancer practices, and it uses genetic and genomic information from cancer tissues to help clinicians choose appropriate targeted therapies for treatment. Most of the targets the tests look for are tumor markers. The example Dodson (2017) provided was HER2 overexpression in breast cancer, which is associated with improved median survival and decreased risk of death when trastuzumab is used in metastatic breast cancer.
For more information about pharmacogenomics in cancer care, refer to Dodson’s full article.
This monthly feature offers readers a concise recap of full-length articles published in the Clinical Journal of Oncology Nursing (CJON) or Oncology Nursing Forum. This edition summarizes “Pharmacogenomics: Principles and Relevance to Oncology Nursing,” by Crystal H. Dodson, PhD, RN, BC-ADM, which was published in the December 2017 issue of CJON. Questions regarding the information presented in this article should be directed to the CJON editor at CJONEditor@ons.org. Photocopying of this article for educational purposes and group discussion is permitted