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Milestone 24

Precision weapons

Targeted cancer therapy

Nature Reviews Cancer volume 6, pages S22–S23 (2006)Cite this article

The first of these molecular-targeted treatments was a monoclonal antibody called trastuzumab (Herceptin; Genentech). Trastuzumab blocks the human epidermal growth factor receptor 2 (HER2) protein that is overexpressed by gene amplification in around 25% of breast cancer cases. Patients with this form of breast cancer have a worse prognosis; however, in the first trial carried out with trastuzumab, Dennis Slamon and colleagues found that women with advanced breast cancer who received the new drug as well as the usual chemotherapy fared better than those who received chemotherapy alone.

If trastuzumab proved that molecular-targeted treatments could effectively treat cancer, then a drug for chronic myeloid leukaemia (CML) called imatinib mesylate (Glivec; Novartis) changed our thinking about the power of designing such therapies. CML is a rare cancer that is characterized by the union of chromosomes 9 and 22, which fuses two genes called breakpoint cluster region ( BCR ) and Abelson murine leukaemia viral oncogene homologue 1 (ABL; also known as ABL1 ), to form a tyrosine kinase that signals myeloid cells to grow and proliferate continuously (see Milestone 10). Imatinib mesylate was rationally designed to block the BCR–ABL active site, and when Brian Druker and colleagues carried out the first trial with the drug they found that almost all patients (98%) with therapy-resistant CML saw their blood counts return to normal. Yet, it turns out that imatinib mesylate is not as selective as first thought, and this promiscuity could help to treat other cancers. George Demetri and colleagues were the first to show that imatinib mesylate could treat patients with advanced gastrointestinal stromal tumours by blocking c-KIT.

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ORIGINAL RESEARCH PAPERS

  1. Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783–792 (2001)

    Article  CAS  Google Scholar 

  2. Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR–ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031–1037 (2001)

    Article  CAS  Google Scholar 

  3. Demetri, G. D. et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med. 347, 472–480 (2002)

    Article  CAS  Google Scholar 

  4. Lynch, T. J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129–2139 (2004)

    Article  CAS  Google Scholar 

  5. Gorre, M. E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR–ABL gene mutation or amplification. Science 293, 876–880 (2001)

    Article  CAS  Google Scholar 

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  1. News Editor, Nature Reviews Drug Discovery,

    Simon Frantz

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  1. Simon Frantz
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Frantz, S. Precision weapons. Nat Rev Cancer 6 (Suppl 1), S22–S23 (2006). https://doi.org/10.1038/nrc1866

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