The Insulin-like Growth Factor (IGF) family and associated receptors are being investigated for relevance to gastrointestinal stromal tumor (GIST).  Pediatric GISTs and other wild-type GISTs (no mutations in the genes for KIT or PDGFRA) are most lkely to involve IGF signalling. 

For summaries about the insulin-like growth factor (IGF) signaling family, please link to these pages on our site:

• IGF Signals in GIST
• Insulin-like Growth Factor 1 Receptor in GIST

Several drugs aimed at inhibiting IGF family targets are in clinical trials at present, and more drugs are expected to enter trials soon.  Although many of these trials are intended for other types of cancer (not GIST), patients with GIST appear to be eligible for the following trials. 

CP-751,871   

manufacturer and mfg website link:  Pfizer 

oral or intravenous: Intravenous

Description: CP-751871 is a human monoclonal antibody directed against the insulin-like growth factor type I receptor (IGF1R) with potential antineoplastic activity. CP-751871 selectively binds to IGF1R, preventing insulin-like growth factor type 1 (IGF1) from binding to the receptor and subsequent receptor autophosphorylation. Inhibition of IGF1R autophosphorylation may result in a reduction in receptor expression on tumor cells that express IGF1R, a reduction in the anti-apoptotic effect of IGF, and inhibition of tumor growth. IGF1R is a receptor tyrosine kinase expressed on most tumor cells and is involved in mitogenesis, angiogenesis, and tumor cell survival.

Ongoing Trials:  One trial which could potentially enroll  a GIST patient is listed below:

Study Of Anti-IGF-IR CP-751,871 In Patients With Solid Tumors  (NCT00474760)

There are additional numerous trials, both Phase I AND phase II,  of this drug for other cancers (lung, breast, prostate, and colorectal).

R1507

manufacturer website link:  Roche / Genmab

oral or intravenous: Intravenous

Description: A recombinant, fully human monoclonal antibody directed against the insulin-like growth factor-1 receptor (IGF-1R) with potential antineoplastic activity. Anti-IGF-1R human monoclonal antibody R1507 binds to membrane-bound IGF-1R, preventing the binding of the natural ligand IGF-1 and the activation of PI3K/AKT signal transduction; downregulation of the PI3K/AKT survival pathway may result in the induction of apoptosis and decreased cellular proliferation. The activation of IGF-1R, a receptor tyrosine kinase of the insulin receptor superfamily, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been implicated in tumorigenesis and metastasis.

Ongoing Trials:

A Study of R1507 in Patients With Recurrent or Refractory Sarcoma (Phase II, NCT00615680)

A Study of R1507 in Patients With Recurrent or Refractory Sarcoma (NCT00642941)

A Multiple Ascending Dose Study of R1507 in Children and Adolescents With Advanced Solid Tumors
(NCT00560144)

A Multiple Ascending Dose Study of R1507 in Patients With Advanced Solid Tumors.  (NCT00400361)

OSI-906 

manufacturer website link  http://www.osip.com/OSI_906

oral or intravenous: Oral

Description from NCI Drug Dictionary: An orally bioavailable small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. IGF-1R inhibitor OSI-906 selectively inhibits IGF-1R, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Overexpressed in a variety of human cancers, IGFR-1 stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis.

Trials (Phase 1) 

Phase 1 Study of Continuous OSI-906 Dosing  (NCT00514007)

Phase 1 Study of Intermittent OSI-906 Dosing  (NCT00514306)