Oday Hamid1. 1. Pfizer Global Research and Development, Ann Arbor Laboratory, Ann Arbor, Mich 48105, USA. Oday.Hamid@pfizer.com
Abstract
OBJECTIVE: To describe the role of tyrosine kinase (TK) and its subreceptors in the development of cancer and the role of TK inhibitors in cancer treatment. DATA SOURCES: Published articles identified through MEDLINE using search terms such as tyrosine kinase, erbB1, erbB2, erbB3, erbB4, epidermal growth factor receptors (EGFR), and EGFR inhibitors. Additional sources were identified from bibliographies in the articles and from Web sites and reports from the National Cancer Institute, American Society of Clinical Oncology, and European Organization for Research and Treatment of Cancer. DATA SYNTHESIS: Progress in identifying the biochemical and molecular causes of cancer has led to discovery of abnormalities that characterize cancer cells and represent targets for development of drug therapies. TK receptors represent one such target when these are present in elevated quantities and/or aberrant forms. Abnormalities in these cell surface receptors have been correlated with development and progression of cancer, poor response to chemotherapeutic agents, and low survival rates. Several subtypes of TK receptors have been identified, and mutations in these have been associated with neoplasms of the breast, lung, colon, ovaries, and other organs. Approved agents, such as trastuzumab (Herceptin-Genentech) work by blocking a subtype of TK receptors that has been associated with breast cancer growth. Gefitinib (Iressa-AstraZeneca) was recently approved for treatment of non-small-cell lung cancer in patients who have failed treatment with traditional chemotherapeutic agents. Other agents such as cetuximab, erlotinib, and canertinib are in advanced stages of clinical trials and may be available for general clinical use in the next few years. CONCLUSION: Cancer continues to be a difficult disease to treat, but newly identified cellular targets have resulted in new medications, and these promising agents are giving hope for additional options for patients with various solid tumors.
OBJECTIVE: To describe the role of tyrosine kinase (TK) and its subreceptors in the development of cancer and the role of TK inhibitors in cancer treatment. DATA SOURCES: Published articles identified through MEDLINE using search terms such as tyrosine kinase, erbB1, erbB2, erbB3, erbB4, epidermal growth factor receptors (EGFR), and EGFR inhibitors. Additional sources were identified from bibliographies in the articles and from Web sites and reports from the National Cancer Institute, American Society of Clinical Oncology, and European Organization for Research and Treatment of Cancer. DATA SYNTHESIS: Progress in identifying the biochemical and molecular causes of cancer has led to discovery of abnormalities that characterize cancer cells and represent targets for development of drug therapies. TK receptors represent one such target when these are present in elevated quantities and/or aberrant forms. Abnormalities in these cell surface receptors have been correlated with development and progression of cancer, poor response to chemotherapeutic agents, and low survival rates. Several subtypes of TK receptors have been identified, and mutations in these have been associated with neoplasms of the breast, lung, colon, ovaries, and other organs. Approved agents, such as trastuzumab (Herceptin-Genentech) work by blocking a subtype of TK receptors that has been associated with breast cancer growth. Gefitinib (Iressa-AstraZeneca) was recently approved for treatment of non-small-cell lung cancer in patients who have failed treatment with traditional chemotherapeutic agents. Other agents such as cetuximab, erlotinib, and canertinib are in advanced stages of clinical trials and may be available for general clinical use in the next few years. CONCLUSION:Cancer continues to be a difficult disease to treat, but newly identified cellular targets have resulted in new medications, and these promising agents are giving hope for additional options for patients with various solid tumors.