Foreword

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Anticancer drug development is undergoing a radical change. The past era of non-specific cytotoxic “classical” chemotherapy is being supplanted by the rational discovery and design of new molecularly targeted agents. This revolutionary change is driven, in large part, by fundamental advances in our understanding of molecular oncology. The sequencing of the human genome and the elucidation of key signaling pathways involved in neoplastic cell proliferation and survival has uncovered a plethora of novel new targets for pharmacological intervention. Agents that affect these new targets have, in some cases, yielded impressive antitumor activity with minimal treatment related toxicities. Outstanding examples of these new class of drugs include imatinib (Gleevec™) which inhibits the bcr-abl and c-kit tyrosine kinases, or gefitinib (Iressa™) and erlotinib (Tarceva™), which inhibit the epidermal growth factor receptor (EGFR) tyrosine kinase. In addition, these specifically targeted therapies have mandated new paradigms for clinical drug development. In previous issues of Current Problems in Cancer, novel agents such as the EGFR inhibitors that target the growth and proliferation signaling pathways have been described in detail. In this issue, Drs. Mita and Tolcher outline another important pathway for therapeutic intervention, the apoptotic or “programmed cell death” pathway. A hallmark of the malignant cell is the ability to circumvent the elaborate machinery responsible for orderly controlled cell death. Acquired defects in apoptosis in tumor cells can have lethal consequences for the host patient. Early clinical development of agents targeting apoptotic pathways is highly promising and there is great expectation that this exciting area of research will yield clinically useful antineoplastic agents in the very near future.