Chapter 1 - Preclinical Drug Development: Translating Basic Research into Clinical Work
Modern drug development in oncology relies on the identification of molecular changes that drive the malignant transformation and are responsible for the development and progression of cancer. This is now possible through improvements in our knowledge of the biology of cancer. The development of new cancer therapeutics has been, however, slow and inefficient; as such, alternative strategies are needed. Preclinical studies are important by providing information that is necessary for the subsequent clinical development of any new anti-cancer agent. Data generated from relevant cell lines and xenograft models are crucial to facilitate a better understanding of the agent’s target, mechanism of action, anti-tumour activity against different tumour types, pharmacology, and toxicology, before entering human clinical testing. The use of preclinical models that more closely reflect the biology of human cancer will help to improve the success rate of new anti-cancer compounds. Finally, the discovery of predictive biomarkers of response, their development in preclinical studies, and their subsequent validation in clinical studies will help to define patient populations most likely to benefit from future treatments.
Further Reading
- Damia G, D’Incalci M. Contemporary pre-clinical development of anticancer agents - What are the optimal preclinical models? Eur J Cancer 2009; 45:2768–2781.
- Garcia V.M., Cassier P.A., de Bono J. Parallel anticancer drug development andmolecular stratification to qualify predictive biomarkers: dealing with obstacles hindering progress. Cancer Discovery 2011; 1:207–212.
- Le Tourneau C, Stathis A, Vidal L, et al. Choice of starting dose for molecularly targeted agents evaluated in first-in-human phase I cancer clinical trials. J Clin Oncol 2010; 28:1401–1407.
- Ocana A, Pandiella A, Siu L.L., et al. Preclinical development of molecular-targeted agents for cancer. Nat Rev Clin Oncol 2010; 8:200–209.
- Politi K, Pao W. How genetically engineered mouse tumor models provide insights into human cancers. J Clin Oncol 2011; 29:2273–2281.
- Senderowicz A.M. Information needed to conduct first-in-human oncology trials in the United States: a view from a former FDA medical reviewer. Clin Cancer Res 2010; 16:1719–1725.
- Spigel D.R., Ervin T.J., Ramlau R, et al. Final efficacy results from OAM4558g, a randomized phase II study evaluating MetMAb or placebo in combination with erlotinib in advanced NSCLC. J Clin Oncol 2011; 29(Suppl): Abstr 7505.
