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Pharmacogenomics, Pharmacokinetics, and Pharmacodynamics in the Era of Targeted Therapies

Emiliano Calvo1, Christine Walko1, E Claire Dees1

  • 1From the DeBartolo Family Personalized Medicine Institute, H. Lee Moffitt Cancer Center, Tampa, FL; UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Platform of Oncology, Hospital Quirón, Torrevieja, Alicante, Spain; START Madrid, Early Clinical Drug Development Program, Centro Integral Oncológico Clara Campal, Madrid, Spain.

American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting
|June 2, 2016
PubMed

Insights

Optimizing cancer treatment involves understanding pharmacogenomic, pharmacokinetic, and pharmacodynamic factors. Personalized medicine requires considering patient variability for better antitumor activity and tolerance.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Cancer therapeutics increasingly utilize targeted agents, presenting challenges for individualized precision medicine.
  • Interpatient variability in drug response, especially with novel agents, is influenced by pharmacogenomic (PG), pharmacokinetic (PK), and pharmacodynamic (PD) factors.

Purpose of the Study:

  • To emphasize the importance of considering PG, PK, and PD factors in drug selection and dosing for optimizing cancer treatment outcomes.
  • To highlight the utility of somatic genetic evaluation for predicting treatment response and guiding therapy post-resistance.
  • To advocate for the integration of therapeutic drug monitoring (TDM) and frailty assessments in clinical practice and drug development.

Main Methods:

  • Review of current literature on cancer pharmacogenomics, pharmacokinetics, and pharmacodynamics.
  • Analysis of the role of somatic genetic evaluation in predicting targeted therapy response and acquired resistance.
  • Discussion on the necessity of therapeutic drug monitoring for novel small molecules and monoclonal antibodies.
  • Exploration of incorporating frailty assessment tools and dose adjustments in clinical trials for vulnerable populations.

Main Results:

  • Pharmacogenomic, pharmacokinetic, and pharmacodynamic factors significantly contribute to interpatient variability in cancer drug action.
  • Somatic genetic tumor evaluation aids in predicting initial response and managing acquired resistance to targeted therapies.
  • Therapeutic drug monitoring is crucial for minimizing the clinical impact of pharmacokinetic variability, particularly in fragile patients.

Conclusions:

  • Personalized cancer therapy necessitates integrating PG, PK, and PD data for optimal drug selection and dosing.
  • Somatic genetic profiling and TDM are essential tools for enhancing antitumor activity and treatment tolerance.
  • Further drug development should include frailty assessments and validate frailty-based dose adjustments for improved outcomes in vulnerable patient groups.

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