Therapeutic Targeting of Cancer Cells: Era of Molecularly Targeted Agents

Recent advances in cancer genomics and proteomics, and the emergence of rapid and cost-efficient genomic profiling methods, have accelerated the development of molecularly targeted agents (MTAs) with the goal of targeting unique molecular features of cancer cells while sparing normal cells. Successful development of MTAs may require different strategies than those traditionally used for the development of conventional cytotoxic chemotherapeutic agents, as the optimal biologic dose may be appreciably different from the maximum tolerated dose. The upsurge in the number of MTAs over the past decade has created new challenges with regard to dose determination and efficacy evaluation, requiring close alignment of laboratory and clinical research with ongoing assessment of pharmacokinetic and pharmacodynamic data for real-time guidance of dosing decisions. Future trial designs of MTAs may need to rely more on pharmacodynamic endpoints as markers or surrogates for antitumor effect rather than on toxicity. Evolution of optimal development of MTAs will see the emergence of individualized cancer therapeutics with the goal of producing more effective and less toxic anticancer therapies.