[Possibilities and limitations of stratified medicine based on biomarkers and targeted therapies in oncology].
Research over the past two decades has untangled the molecular heterogeneity of cancer at the cellular level. The molecular techniques that have been developed in the past 5 to 10 years are dramatically improving our understanding of the genomic aberrations that underlie the malignant transformation of normal cells. At the same time, however, advances in our understanding of the genetic basis of solid tumours and hematologic malignancies have revealed how complex cancer is, and consequently how much more challenging it is in many of the more common cancers to identify the right drug for the right patient in the adequate dose at the right time. Given the slow pace of translation from genome science to individualised medicine in oncology, this expert review, mainly taking into account recently published perspective articles and reviews, describes the molecular heterogeneity of cancer, the difficulties in developing novel molecularly targeted agents, and the need for developing biomarkers to optimise drug development and clinical use. Distinct types of biomarkers, breakthroughs as well as disappointments in the clinical implementation of biomarkers and targeted therapeutics into clinical practice are discussed by focusing on four targeted anti-cancer drugs. Finally, as clinical biomarker tests that predict response to particular therapies will play an important role in achieving stratified medicine in the near future, this article will conclude by giving some recommendations for effective biomarker evaluation and clinical trial designs for predictive biomarker validation.
Klinik für Hämatologie, Onkologie und Tumorimmunologie im HELIOS Klinikum Berlin-Buch. wolf-dieter.ludwig@helios-kliniken.de
Wolf-Dieter
WD
Ludwig
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001688:Biological Products / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics; D019317:Evidence-Based Medicine / Q000379:methods*; D018740:Genetic Heterogeneity / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D057285:Precision Medicine / Q000379:methods*; D011379:Prognosis
D000970:Antineoplastic Agents; D001688:Biological Products; D014408:Biomarkers, Tumor