Pharmacological Profile and Pharmacogenomics of Anti-Cancer Drugs Used for Targeted Therapy.
Drugs for targeted therapies are primarily Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA molecules and microRNA. The use of these new agents generates a multifaceted step in the pharmacokinetics (PK) of these drugs. Individual PK variability is often large, and unpredictability observed in the response to the pharmacogenetic profile of the patient (e.g. cytochome P450 enzyme), patient characteristics such as adherence to treatment and environmental factors.



This review aims to overview the latest anticancer drugs eligible for targeted therapies and the most recent finding in pharmacogenomics related to toxicity/resistance of either individual gene polymorphisms or acquired mutation in a cancer cell. In addition, an early outline evaluation of the genotyping costs and methods has been taken into consideration. Future Outlook: To date, therapeutic drug monitoring (TDM) of mAbs and SMIs is not yet supported by heavy scientific evidence. Extensive effort should be made for targeted therapies to better define concentration-effect relationships and to perform comparative randomized trials of classic dosing versus PK-guided adaptive dosing. The detection of individual pharmacogenomics profile could be the key for the oncologists that will have new resources to make treatment decisions for their patients in order to maximize the benefit and minimize the toxicity. Based on this purpose, the clinician should evaluate advantages and limitations, in terms of costs and applicability, of the most appropriate pharmacological approach to performing a tailored therapy.
Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples, Italy.
Raffaele
R
Di Francia
Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples, Italy.
Angela
A
De Monaco
Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples, Italy.
Mariangela
M
Saggese
Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples, Italy.
Giancarla
G
Iaccarino
Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples, Italy.
Stefania
S
Crisci
Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples, Italy.
Ferdinando
F
Frigeri
Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
Rosaria
R
De Filippi
Department of Medical Oncology; CRO National Cancer Institute, Aviano (PN), Italy.
Massimiliano
M
Berretta
Hematology-Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Fondazione "G. Pascale" IRCCS, Naples, Italy.
Antonio
A
Pinto
D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016903:Drug Monitoring; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D011379:Prognosis; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins
Anticancer mAbs; cancer cell; personalized medicine; pharmacogenomics; tailored therapy; tyrosine kinase inhibitors.