Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Cancer, obesity, and diabetes: TKIs exert multiple effects on glucose homeostasis

Nature Reviews Clinical Oncology volume 14, page 268 (2017)Cite this article

Subjects

Cancer, obesity, and type II diabetes mellitus (T2DM) are becoming increasingly prevalent worldwide; a greater understanding of the links between these medical conditions is urgently needed in order to identify novel targets for treatment. In a Review published in the February 2017 issue of this distinguished journal (Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing? Nat. Rev. Clin. Oncol. 14, 82–99; 2017)1, Klil-Drori et al. summarize the current evidence regarding the relationships between obesity, T2DM, and cancer. We completely agree with the authors' statements regarding the influence of various medications used to treat diabetes on cancer development and/or outcomes. Moreover, we appreciate the clear evidence presented by the authors that, conversely, some anticancer treatments can perturb glucose homeostasis and, therefore, lead to or exacerbate hyperglycaemia and T2DM. This Review neglects, however, the potential effects of tyrosine-kinase inhibitors (TKIs) that are used routinely in the treatment of cancer on glycaemic control.

TKIs are now used successfully in the treatment of many malignancies. Many of these agents target signalling pathways that influence cellular glucose metabolism, and increasing amounts of data demonstrate that TKI therapy can result in either elevated or decreased blood glucose levels, depending on the agent used and the clinical context2,3 (Table 1). In some settings, hyperglycaemia has been reported as a common adverse effect of TKI therapy4. Generally, however, TKIs contribute to lower glucose level and, thus, improve glycaemic control. In one study5, the hypoglycaemic effects of imatinib, dasatinib, sorafenib, and sunitinib occurred in both diabetic and nondiabetic patients, but the exact underlying mechanisms remain to be determined. Importantly, this effect might actually be beneficial for patients with T2DM by enabling them to discontinue antidiabetic drugs; in the aforementioned study5, eight of the 17 diabetic patients (47%) attained a level of glycaemic control with TKI therapy that enabled them to discontinue their antidiabetic medications, including insulin in some patients.

Table 1 Effect of TKIs approved for the treatment of cancer on glucose homeostasis
Full size table

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Klil-Drori, A. J., Azoulay, L. & Pollak, M. N. Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing? Nat. Rev. Clin. Oncol. 14, 85–99 (2017).

    Article  CAS  Google Scholar 

  2. Shlomai, G., Neel, B., LeRoith, D. & Gallagher, E. J. Type 2 diabetes mellitus and cancer: the role of pharmacotherapy. J. Clin. Oncol. 34, 4261–4269 (2016).

    Article  CAS  Google Scholar 

  3. Malek, R. & Davis, S. N. Tyrosine kinase inhibitors under investigation for the treatment of type II diabetes. Expert Opin. Investig. Drugs 25, 287–296 (2016).

    Article  CAS  Google Scholar 

  4. Saglio, G. et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N. Engl. J. Med. 362, 2251–2259 (2010).

    Article  CAS  Google Scholar 

  5. Agostino, N. M. et al. Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice. J. Oncol. Pharm. Pract. 17, 197–202 (2011).

    Article  CAS  Google Scholar 

  6. Verges, B., Walter, T. & Cariou, B. Endocrine side effects of anti-cancer drugs: effects of anti-cancer targeted therapies on lipid and glucose metabolism. Eur. J. Endocrinol. 170, R43–R55 (2014).

    Article  CAS  Google Scholar 

  7. Lodish, M. B. & Stratakis, C. A. Endocrine side effects of broad-acting kinase inhibitors. Endocr. Relat. Cancer 17, R233–R244 (2010).

    Article  CAS  Google Scholar 

  8. Le Jeune, S. et al. Refractory hypoglycemia controlled by sorafenib in solitary fibrous tumor. J. Clin. Oncol. 31, e118–e121 (2013).

    Article  Google Scholar 

  9. Lee, S. W. et al. Recurrent hypoglycemia triggered by sorafenib therapy in a patient with hemangiopericytoma. Endocrinol. Metab. (Seoul) 29, 202–205 (2014).

    Article  Google Scholar 

  10. Veneri, D., Franchini, M. & Bonora, E. Imatinib and regression of type 2 diabetes. N. Engl. J. Med. 352, 1049–1050 (2005).

    Article  CAS  Google Scholar 

  11. Ono, K. et al. Rapid amelioration of hyperglycemia facilitated by dasatinib in a chronic myeloid leukemia patient with type 2 diabetes mellitus. Intern. Med. 51, 2763–2766 (2012).

    Article  Google Scholar 

  12. Simon, G. R. et al. Phase 2 trial of docetaxel and gefitinib in the first-line treatment of patients with advanced nonsmall-cell lung cancer (NSCLC) who are 70 years of age or older. Cancer 112, 2021–2029 (2008).

    Article  CAS  Google Scholar 

  13. Costa, D. B. & Huberman, M. S. Improvement of type 2 diabetes in a lung cancer patient treated with erlotinib. Diabetes Care 29, 1711 (2006).

    Article  Google Scholar 

  14. Motzer, R. J. et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med. 356, 115–124 (2007).

    Article  CAS  Google Scholar 

  15. Oh, J. J. et al. Impact of sunitinib treatment on blood glucose levels in patients with metastatic renal cell carcinoma. Jpn J. Clin. Oncol. 42, 314–317 (2012).

    Article  Google Scholar 

Download references

Acknowledgements

The work of the J.J. is supported by grants from the National Natural Science Foundation of China (81572738), the Natural Science Foundation of Guangxi (2015GXNSFEA139003), and the Lijiang Scholar Award.

Author information

Authors and Affiliations

  1. Minglin Lin and Junfei Jin are at the Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, 15 Lequn Road, Guilin, 541001, Guangxi, China.,

    Minglin Lin & Junfei Jin

Authors
  1. Minglin Lin
    View author publications

    Search author on:PubMed Google Scholar

  2. Junfei Jin
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Junfei Jin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, M., Jin, J. Cancer, obesity, and diabetes: TKIs exert multiple effects on glucose homeostasis. Nat Rev Clin Oncol 14, 268 (2017). https://doi.org/10.1038/nrclinonc.2017.56

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/nrclinonc.2017.56

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer