Targeting the insulin growth factor pathway in gastrointestinal cancers

  • Golan T
  • Javle M
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Abstract

Insulin-like growth factor 1 (IGF-1)-directed therapy is currently at a crossroads. After decades of research, several agents targeting the IGF pathway are now in clinical trials. One recent phase III trial of the IGF-1R inhibitor figitumumab in patients with non-small-cell lung cancer was discontinued after an interim analysis showed no survival improvement. Clinical trials for patients with sarcoma have demonstrated impressive anti-tumor activity in cases where the IGF-1 pathway is activated, such as in Ewing sarcoma; however, acquired resistance has been common. Recently, randomized phase II trials combining IGF-1R with epidermal grown factor receptor (EGFR) inhibition in colorectal cancer have been completed. Preclinical studies have indicated that several biomarkers may have potential predictive value. Studies of IGF-1R inhibitors in gastrointestinal cancers are currently ongoing in pancreatic, gastroesophageal, hepatocellular, and colorectal cancers. A critical analysis of prior work in this field and a rational strategy for maximizing success on the basis of biomarker use are necessary.

Author-supplied keywords

  • 1 [4 [(5 cyclopropyl 1h pyrazol 3 yl)amino]pyrrolo
  • Ewing sarcoma
  • amg 479
  • antineoplastic agent
  • article
  • binding affinity
  • bms 754807
  • cancer risk
  • cancer staging
  • carboplatin
  • carcinogenesis
  • cetuximab
  • cixutumumab
  • colorectal cancer
  • conatumumab
  • cp 751 871
  • dalotuzumab
  • dehydration
  • digestive system cancer
  • dose response
  • drug efficacy
  • drug mechanism
  • drug targeting
  • drug tolerability
  • erbitux
  • erlotinib
  • fatigue
  • fever
  • figitumumab
  • ganitumab
  • gemcitabine
  • gemzar
  • human
  • hyperglycemia
  • imc a 12
  • injection site reaction
  • intracellular signaling
  • irinotecan
  • linsitinib
  • mk 0646
  • neuroendocrine tumor
  • neutropenia
  • non small cell lung cancer
  • osi 906
  • paclitaxel
  • pancreas cancer
  • protein binding
  • protein expression
  • protein function
  • protein tyrosine kinase inhibitor
  • r 1507
  • robatumumab
  • sch 717454
  • single nucleotide polymorphism
  • somatomedin C receptor
  • tarceva
  • thrombocytopenia
  • unclassified drug

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Authors

  • T Golan

  • M Javle

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