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Ortho Biotech Oncology Research and Development, a Division of Johnson and Johnson, Raritan, New Jersey
Requests for reprints: William N. Hait, Ortho Biotech Oncology Research and Development, J&J PRD Building, 920 Route 202, Raritan, NJ 08869. Phone: 9089273516; Fax: 9089277716; E-mail: WHait{at}ITS.JNJ.COM.
Targeted therapies can be defined as drugs developed against a specific target based on its important biological function in cancer. In contrast, nontargeted therapies are drugs identified by phenotypic screening of natural products or chemical libraries against established cancer cell lines or preclinical animal models without a priori knowledge of the target. Targeted therapies are designed to selectively inhibit a target that is abnormal in malignant compared with normal tissues; these drugs often affect proximal events in signaling pathways that drive abnormal growth and have relatively low toxicity. In contrast, nontargeted therapies affect proteins or nucleic acids that may or may not be abnormal in malignant compared with normal tissues; these drugs often target the downstream consequences of activated signaling pathways, e.g., DNA synthesis and microtubule assembly, and are toxic. Whereas targeted therapies are highly effective in selected hematopoietic malignancies, most have shown limited efficacy against complex solid tumors. In contrast, nontargeted drugs include some of the most effective yet most toxic drugs in the oncology pharmacopoeia. In the future, advances in genomics, proteomics, biology, biomarkers, chemistry, and protein engineering will coalesce to accelerate the development of increasingly selective and effective targeted therapies. Understanding the target in context will help identify biomarkers predictive of response. Finally, a detailed understanding of the target's structure and function will help anticipate and identify mechanism of drug resistance and help design drugs and combinations of drugs that retain activity. [Cancer Res 2009;69(4):1263–7]
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Ortho Biotech Oncology Research and Development, a Division of Johnson and Johnson, Raritan, New Jersey
Requests for reprints: William N. Hait, Ortho Biotech Oncology Research and Development, J&J PRD Building, 920 Route 202, Raritan, NJ 08869. Phone: 9089273516; Fax: 9089277716; E-mail: WHait{at}ITS.JNJ.COM.
Targeted therapies can be defined as drugs developed against a specific target based on its important biological function in cancer. In contrast, nontargeted therapies are drugs identified by phenotypic screening of natural products or chemical libraries against established cancer cell lines or preclinical animal models without a priori knowledge of the target. Targeted therapies are designed to selectively inhibit a target that is abnormal in malignant compared with normal tissues; these drugs often affect proximal events in signaling pathways that drive abnormal growth and have relatively low toxicity. In contrast, nontargeted therapies affect proteins or nucleic acids that may or may not be abnormal in malignant compared with normal tissues; these drugs often target the downstream consequences of activated signaling pathways, e.g., DNA synthesis and microtubule assembly, and are toxic. Whereas targeted therapies are highly effective in selected hematopoietic malignancies, most have shown limited efficacy against complex solid tumors. In contrast, nontargeted drugs include some of the most effective yet most toxic drugs in the oncology pharmacopoeia. In the future, advances in genomics, proteomics, biology, biomarkers, chemistry, and protein engineering will coalesce to accelerate the development of increasingly selective and effective targeted therapies. Understanding the target in context will help identify biomarkers predictive of response. Finally, a detailed understanding of the target's structure and function will help anticipate and identify mechanism of drug resistance and help design drugs and combinations of drugs that retain activity. [Cancer Res 2009;69(4):1263–7]
School of Chemistry, The University of Sydney, Sydney, Australia
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