Related Experiment Video

Updated: May 28, 2026

Ex Vivo Culture of Circulating Tumor Cells in the Cerebral Spinal Fluid from Melanoma Patients to Study Melanoma-Associated Leptomeningeal Disease
06:25

Ex Vivo Culture of Circulating Tumor Cells in the Cerebral Spinal Fluid from Melanoma Patients to Study Melanoma-Associated Leptomeningeal Disease

Published on: March 29, 2024

Insulin-like growth factor receptor expression is associated with aggressive phenotypes and has therapeutic activity

Hirokazu Ohashi1, Yasushi Adachi, Hiroyuki Yamamoto

  • 1First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan.

Cancer Science
|November 3, 2011
PubMed

Insights

Targeting the Insulin-like Growth Factor I Receptor (IGF-IR) pathway shows promise for treating biliary tract carcinomas (BTC). Blocking IGF-IR effectively reduced tumor growth and increased chemotherapy sensitivity in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Insulin-like Growth Factor I Receptor (IGF-IR) signaling is crucial for various cancer progressions.
  • Its role in biliary tract carcinomas (BTC) and therapeutic potential remain underexplored.

Purpose of the Study:

  • To investigate the expression of IGF axis components in BTC.
  • To evaluate the efficacy of IGF-IR blockade as a therapeutic strategy in BTC models.

Main Methods:

  • Immunohistochemical analysis of IGF axis elements, matrilysin, p53, and IGFBP-3 promoter methylation in 80 BTC samples.
  • In vitro studies using BTC cell lines treated with IGF-IR inhibitor BMS-536924 or IGF-IR/dn.
  • In vivo efficacy assessment in nude mouse xenograft models.

Main Results:

  • IGF-IR expression was observed in 69% of BTC, correlating with advanced stage and matrilysin.
  • BMS-536924 effectively inhibited IGF-IR signaling, suppressed proliferation, and enhanced chemotherapy-induced apoptosis in vitro.
  • IGF-IR blockade demonstrated significant anti-tumor activity in vivo.

Conclusions:

  • IGF-IR is a potential biomarker for aggressive BTC and a viable therapeutic target.
  • The IGF-IR inhibitor BMS-536924 shows significant therapeutic promise for BTC treatment.

More Related Videos

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT10:28

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT

Published on: January 22, 2018

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...