Drugs have different effects on different people, and pharmacogenomics is the study of how a drug’s effects vary by the genetics of the patient.  Why might we want this information? Individual response to drugs can help drug developers come up with medicines that will have greater impact or benefit more patients.  It can explain why some medicines work on a set of patients but not on another set.  And it can help doctors choose the best regimen for a given case, possibly lowering risk of serious side effects and lowering cost.

The results of a detailed genetic analysis and knowledge of the broader science may enable the treating physician to better choose a drug regimen or to better establish the best dosage.

The website of the American Society of Clinical Oncology stresses that pharmacogenetics is different from gene testing that many patients with breast cancer get.  Breast cancer and sometimes other cancers are classified by whether the patient has particular genes – BRCA1 and BRCA2 genes for instance.  Pharmacogenetics is more subtle – looks for possible interactions among genes. 

Pharmacogenetics can help in treatment of acute lymphoblastic leukemia . Some people have a genetic variation that results in lower levels of the enzyme thiopurine methyltransferase (TPMT). Patients with low levels of this enzyme (or the genetic indicator that suggests low levels) may be given lower doses of chemotherapy.

The UGT1A1 test can be used to determine whether colon cancer patients have an enzyme that breaks down the chemotherapy drug irinotecan. The results of this test can help the health care team decide the appropriate dosage.

Analysis of the tumor or the healthy tissue?

Tumors can have mutations that make their genome differ from the rest of the body.  Does pharmacogenomics call for the analysis of the tumor or of the germline?  Both are possible, but most of the time you’re interested in the germline.  Can the body process the chemo agent? Is a question doctors ask and analysis of the germline 

Germline analysis is often done on blood cells, unless the patient has blood cancer in which case a cell from the saliva is used.

So far, pharmacogenomics-influenced treatment of cancer is more promise than reality.  It has had some success in the clinic.  It has identified individuals who have low levels of enzymes that break down the chemotherapy agents mercaptopurine, irinotecan, and fluorouracil.

These are examples where looking at the germline was important, not the tumor genome. The germline results told the doctors whether the patients have high enough enzyme levels to handle the drugs.

In addition to pharmacogenetic considerations, a patient’s reaction to a medicine is affected by factors that include:

• Stage of cancer and size and extent of tumor
• Medications taken for other conditions
• Lifestyle habits, such as smoking and drinking alcohol
• Other diseases (comorbidities)
  • Related to this is whether the patients smokes, level of alcohol consumption
• Sex
• Age

Status and Future

Pharmacogenetics is not widely used in the clinic.  Like other elements of personalized therapy, pharmacogenetics has a lot of people excited about its potential, but it is expensive and not many doctors and scientists know what to do with the information gained from the analysis.  Also, privacy concerns plague discussions and enthusiasm for anything that looks too closely at a person’s genes.

NIH on pharmacogenetics: https://www.genome.gov/FAQ/Pharmacogenomics

Good article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668552/

Article on gene testing: https://www.mayo.edu/research/centers-programs/center-individualized-medicine/patient-care/pharmacogenomics/drug-gene-testing