E-Mail karger@karger.com Review Oncology DOI: 10.1159/000446437 Molecular Targets in Advanced Therapeutics of Cancers: The Role of Pharmacogenetics Murtala B. Abubakar a, b Siew Hua Gan a a Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia; b Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Dan Fodiyo University, Sokoto, Nigeria Introduction For many years, chemotherapy has been the gold stan- dard for the treatment of patients with advanced malig- nancies, such as non-small cell lung carcinoma (NSCLC), metastatic colorectal and metastatic breast cancers. Nev- ertheless, evolving advanced molecular targeted therapy is becoming more and more available and contributes to improving the prognoses for these advanced diseases [1–3]. In contrast to conventional chemotherapies, targeted therapies are specifically directed against molecules that are associated with disease development and its progres- sion (e.g. tumor development and its progression in the case of malignant disease). Some of the established, cur- rently investigated, and potential therapeutic target mol- ecules include: insulin-like growth factor 1 receptor (IGF- 1R) [4–7]; mechanistic target of rapamycin (mTOR) [8– 10]; tyrosine kinases (TKs), such as platelet-derived growth factor receptor (PDGFR) [11, 12] and v-kit Har- dy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) [12]; epidermal growth factor receptors (EGFRs) [13–15]; vascular endothelial growth factor receptors (VEGFRs) [16]; poly (ADP ribose) polymerase 1 (PARP- 1) [17–19]; phosphatidylinositol 3-kinase (PI3K) [17, 20] Key Words Targeted therapy · Molecular targets · Advanced therapeutics · Pharmacogenetics Abstract The advent of advanced molecular targeted therapy has re- sulted in improved prognoses for patients with advanced malignancies. However, despite the significant success and specificity of this advocated targeted therapy, significant on- and off-target adverse effects and inter-individual variability in treatment responses have been reported. The interpatient variability in drug response has been suggested to be partly due to variations in patient genomes. Therefore, the identi- fication of genetic biomarkers by conducting pharmacoge- netics studies can help predict patient responses to targeted therapy and may serve as a basis for individualized treat- ment. In this review, both clinically established and potential molecular targets are highlighted. Overall, current literature suggests that individualization of targeted therapy is prom- ising; however, integrating the clinical benefits of identified biomarkers into clinical practice for personalized medicine remains a major challenge, and further studies to validate these markers and identify novel therapeutic approaches are needed. © 2016 S. Karger AG, Basel Received: November 23, 2015 Accepted after revision: April 25, 2016 Published online: May 27, 2016 Dr. Murtala B. Abubakar Human Genome Centre, School of Medical Sciences Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150 Kota Bharu (Malaysia) E-Mail murtalaabubakar704  @  gmail.com © 2016 S. Karger AG, Basel 0030–2414/16/0000–0000$39.50/0 www.karger.com/ocl Downloaded by: University of Cincinnati 129.137.5.42 - 5/27/2016 1:26:27 PM