New targets and challenges in the molecular therapeutics of cancer.
The past 20 years have seen an explosion of information on the molecular changes that lead to cancer. The pathways that have been uncovered include many targets for the development of novel therapeutics. Several such drugs have been approved for clinical use and many additional drugs and targets are now being evaluated in preclinical studies. These new drugs may exhibit impressive therapeutic activity, but this is often restricted to a subpopulation of cancers with a particular molecular change. Moreover, toxicity or even antagonism may result from off-target effects of the drugs. Accordingly, it will be critical to stratify patients for treatment based on the propensity of their tumours to respond. In addition, defining the appropriate dose of targeted agents to administer is challenging; early clinical trial designs must include assays to define the effective biological dose, in addition to more traditional end-points such as the maximum tolerable dose. These and many other challenges exist in the preclinical and clinical development of these drugs.
Eastman
Alan
A
Department of Pharmacology and Toxicology, Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, NH 03756, USA. alan.r.eastman@dartmouth.edu
Perez
Raymond P
RP
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010597:Pharmacogenetics
D000970:Antineoplastic Agents