ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer

Related Experiment Video

Updated: Feb 15, 2026

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
08:12

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer

Published on: March 14, 2019

6.1K

Filippo Pietrantonio1, Federica Di Nicolantonio2,3, Alexa B Schrock4

  • 1Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Journal of the National Cancer Institute
|January 26, 2018
PubMed
Abstract

Insights

Rearrangements in ALK, ROS1, and NTRK genes define a rare, aggressive subtype of metastatic colorectal cancer (mCRC). These genetic alterations are linked to poorer survival and resistance to standard therapies, necessitating targeted treatment approaches.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • ALK, ROS1, and NTRK fusions are identified in a small subset (0.2%-2.4%) of colorectal cancers.
  • Previous reports highlight benefits of targeted therapies (anti-ALK, ROS, TrkA-B-C) in select metastatic colorectal cancer (mCRC) patients with these rearrangements.
  • Characterizing the clinical and molecular profile of rearranged mCRC is crucial for understanding disease behavior and treatment strategies.

Purpose of the Study:

  • To comprehensively analyze the clinical and molecular landscape of ALK, ROS1, and NTRK rearranged metastatic colorectal cancer (mCRC).
  • To compare the characteristics and outcomes of rearranged mCRC patients with those lacking these specific genetic alterations.
  • To evaluate the prognostic significance and potential therapeutic targets in this rare mCRC subtype.

Main Methods:

  • Retrospective analysis of 27 mCRC patients with ALK, ROS1, and NTRK rearrangements.
  • Comparison with a control cohort of 319 mCRC patients without these rearrangements using statistical tests (Fisher's exact, χ2, Mann-Whitney).
  • Survival analysis using Kaplan-Meier and Cox proportional hazard models; deep molecular and immunophenotypic characterization.

Main Results:

  • ALK, ROS1, and NTRK rearrangements were more prevalent in elderly patients with right-sided, node-positive, RAS wild-type, and MSI-high tumors.
  • Patients with these fusions exhibited significantly shorter overall survival (15.6 months) compared to those without (33.7 months).
  • Primary resistance to anti-EGFR agents was observed; MSI-high rearranged tumors frequently showed targetable RNF43 mutations.

Conclusions:

  • ALK, ROS1, and NTRK rearrangements identify a rare mCRC subtype with a very poor prognosis.
  • Tumor site, MSI-high status, and wild-type RAS/BRAF may help identify patients with these alterations.
  • While current treatments show limited efficacy, targeted therapies against ALK, ROS, and TrkA-B-C pathways offer promising therapeutic avenues.

More Related Videos

Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer06:19

Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer

Published on: July 18, 2017

10.8K
Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer06:49

Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer

Published on: February 10, 2023

2.9K

Related Concept Videos

[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement01:21

[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement

The Cope rearrangement is classified as a [3,3] sigmatropic shift in 1,5-dienes, leading to a more stable, isomeric 1,5-diene. The reaction involves a concerted movement of six electrons, four from two π bonds and two from a σ bond, via an energetically favorable chair-like transition state.
3.5K
[3,3] Sigmatropic Rearrangement of Allyl Vinyl Ethers: Claisen Rearrangement01:24

[3,3] Sigmatropic Rearrangement of Allyl Vinyl Ethers: Claisen Rearrangement

The Claisen rearrangement is a [3,3] sigmatropic rearrangement of allyl vinyl ethers to unsaturated carbonyl compounds. The rearrangement is a concerted pericyclic reaction proceeding via a chair-like transition state.
2.9K
Preparation of Diols and Pinacol Rearrangement01:57

Preparation of Diols and Pinacol Rearrangement

Compounds bearing two hydroxyl groups are known as diols. When the hydroxyl groups are located on adjacent carbon atoms, the diols are called vicinal diols or glycols. Under acidic conditions, vicinal diols undergo a specific reaction called pinacol rearrangement.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
4.3K
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism01:26

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism

The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...
4.1K
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview01:07

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.
3.7K
Cancer02:18

Cancer

Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
54.6K