Cancers 2011, 3(3), 3029-3054; doi:10.3390/cancers3033029
Review

Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance

1 Departments of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 2 Departments of Thoracic Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 3 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
* Author to whom correspondence should be addressed.
Received: 10 May 2011; in revised form: 6 July 2011 / Accepted: 19 July 2011 / Published: 26 July 2011
(This article belongs to the Special Issue Cancer Signaling Pathways and Crosstalk)
PDF Full-text Download PDF Full-Text [902 KB, uploaded 26 July 2011 11:14 CEST]
Abstract: The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R) function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients. Though a small subset of patients enrolled within phase I or II clinical trials revealed dramatic clinical response to IGF-1R targeted therapies (most using monoclonal antibodies to IGF-1R), in toto, the anticancer effect has been underwhelming and unsustained, as even those with marked clinical responses seem to rapidly acquire resistance to IGF-1R targeted agents when used alone through yet to be identified mechanisms. As the IGF-1R receptor is just one of many that converge upon common intracellular signaling cascades, it is likely that effective IGF-1R targeting must occur in parallel with blockade of redundant signaling paths. Herein, we present the rationale for dual targeting of IGF-1R and other signaling molecules as an effective strategy to combat acquired drug resistance by carcinomas and sarcomas.
Keywords: IGF-1R; insulin-like growth factor; combination therapy; drug resistance; Ewing sarcoma

Article Statistics

Load and display the download statistics.

Citations to this Article

Cite This Article

MDPI and ACS Style

Ludwig, J.A.; Lamhamedi-Cherradi, S.-E.; Lee, H.-Y.; Naing, A.; Benjamin, R. Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance. Cancers 2011, 3, 3029-3054.

AMA Style

Ludwig JA, Lamhamedi-Cherradi S-E, Lee H-Y, Naing A, Benjamin R. Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance. Cancers. 2011; 3(3):3029-3054.

Chicago/Turabian Style

Ludwig, Joseph A.; Lamhamedi-Cherradi, Salah-Eddine; Lee, Ho-Young; Naing, Aung; Benjamin, Robert. 2011. "Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance." Cancers 3, no. 3: 3029-3054.

Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert