Imatinib and the long tail of targeted drug development

Article metrics

New molecular insights occasionally lead to the rapid development of therapeutic agents that improve the outcomes of patients with cancer; however, these breakthroughs can be followed by extensive, empirically driven and often unsuccessful efforts at extending the drug to other indications or combinations. Herein, we describe the clinical development of imatinib, a paradigm of rapid molecularly driven drug development, and advocate for a balanced portrayal of the potential of molecularly targeted therapies for cancer.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Accumulating evidence and research organization (AERO)8 diagram of published clinical trials of imatinib.


  1. 1.

    TIME. Drugs that fight cancer. TIME,16641,20010528,00.html (2001).

  2. 2.

    Cohen, M. H. et al. Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin. Cancer Res. 8, 935–942 (2002).

  3. 3.

    FDA. Drugs@FDA: FDA approved drug products. FDA (2018).

  4. 4.

    Yam, C. et al. A phase II study of imatinib mesylate and letrozole in patients with hormone receptor-positive metastatic breast cancer expressing c-kit or PDGFR-β. Invest. New Drugs 36, 1103–1109 (2018).

  5. 5.

    Carlisle, B. G. et al. Patient benefit and risk in anticancer drug development: a systematic review of the ixabepilone trial portfolio. medRxiv (2019).

  6. 6.

    Boyiadzis, M. M. et al. Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease. J. Immunother. Cancer 6, 35 (2018).

  7. 7.

    Walker, I. & Newell, H. Do molecularly targeted agents in oncology have reduced attrition rates? Nat. Rev. Drug Discov. 8, 15–16 (2008).

  8. 8.

    Hey, S. P., Heilig, C. M. & Weijer, C. Accumulating Evidence and Research Organization (AERO) model: a new tool for representing, analyzing, and planning a translational research program. Trials 14, 1 (2013).

Download references


The work of J.K. is funded by the Canadian Institutes of Health Research (CIHR; EOG111391). Without in any way implying endorsement of the contents of this article, the authors thank members of STREAM and H. Atkins for helpful consultations.

Author information

Correspondence to Jonathan Kimmelman.

Ethics declarations

Competing interests

The authors declare no competing interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Carlisle, B.G., Zheng, T. & Kimmelman, J. Imatinib and the long tail of targeted drug development. Nat Rev Clin Oncol (2019) doi:10.1038/s41571-019-0287-0

Download citation