Pharmacogenomics and Oncology

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.

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

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