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Clinical evaluation of biologically targeted drugs: Obstacles and opportunities

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Abstract

Recent insights into the molecular mechanisms of cancer have indicated that a variety of fundamental cellular processes are dysregulated in malignant cells. These processes include cell cycle control, signal transduction pathways, apoptosis, telomere stability, angiogenesis, and interactions with the extracellular matrix. Remarkable advances in molecular genetics, enzymology, and medicinal chemistry have permitted the design of compounds that modulate some of these processes with specificity that was unimaginable a decade ago. As these novel, biologically targeted compounds enter the clinic, they will require a strategy for clinical evaluation and development different from that used commonly for cytotoxic antineoplastic agents. This review examines the development of cancer drugs directed against angiogenesis, metastasis, signal transduction, telomerase, and molecular message (anti-sense), outlines strategies for the clinical testing of agents directed at these processes, and contrasts these efforts with traditional approaches to cancer drug testing.

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  1. Massachusetts General Hospital Cancer Center, Boston, MA, USA

    Anthony L. Boral, Scott Dessain & Bruce A. Chabner

  2. Massachusetts General Hospital Cancer Center, Cox Building, 640, 100 Blossom Street, 02114, Boston, MA, USA

    Bruce A. Chabner

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Work presented at the 13th Bristol-Myers Squibb Nagoya International Cancer Treatment Symposium, “Strategic Cross Talk between Major Oncology Groups/Clinical Pharmacology in Cancer Chemotherapy,” 17–18 October 1997, Nagoya, Japan

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Boral, A.L., Dessain, S. & Chabner, B.A. Clinical evaluation of biologically targeted drugs: Obstacles and opportunities. Cancer Chemother Pharmacol 42 (Suppl 1), S3–S21 (1998). https://doi.org/10.1007/s002800051075

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