title: Pharmacogenomics, Pharmacokinetics, and Pharmacodynamics in the Era of Targeted Therapies.
abstract: The complex nature of the pharmacologic aspects of cancer therapeutics has become more apparent in the past several years with the arrival of a cascade of target-based agents and the difficult challenge of bringing individualized precision medicine to oncology. Interpatient variability in drug action, singularly in novel agents, is in part caused by pharmacogenomic (PG), pharmacokinetic, and pharmacodynamic (PD) factors, and drug selection and dosing should take this into consideration to optimize the benefit for our patients in terms of antitumor activity and treatment tolerance. In this regard, somatic genetic evaluation of tumors is useful in not only predicting response to initial targeted therapies but also in anticipating and guiding therapy after the development of acquired resistance; therapeutic drug monitoring of novel small molecules and monoclonal antibodies must be incorporated in our day-to-day practice to minimize the negative effect on clinical outcome of interindividual variability on pharmacokinetic processes of these drugs for all patients, but especially for fragile patient populations and those with organ dysfunction or comorbidities. For these populations, incorporating frailty assessment tools into trials of newer agents and validating frailty-based dose adjustment should be an important part of further drug development.
authors.affiliation: From 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.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Calvo
authors.affiliation: From 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Walko
authors.affiliation: From 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.
authors.forename: E Claire
authors.initials: EC
authors.lastname: Dees
authors.affiliation: From 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.
authors.forename: Belén
authors.initials: B
authors.lastname: Valenzuela
mesh_terms: D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010597:Pharmacogenetics
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor