Related Experiment Video

Updated: Jun 10, 2025

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
10:13

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells

Published on: July 3, 2013

11.1K

Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations

Faiza Yasin1,2, Ethan Sokol3, Neil Vasan4

  • 1Department of Medicine (Medical Oncology), Yale University, New Haven, CT 06510, United States.

The Oncologist
|October 14, 2024
PubMed
Abstract

Insights

Multi-hit PIK3CA mutations occur in 1.7% of advanced colorectal cancer (CRC) patients. This finding identifies a potential patient subset with enhanced sensitivity to PI3K inhibitors for future clinical trials.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Activating mutations in the PIK3CA oncogene are present in approximately 20% of colorectal cancer (CRC) patients.
  • Multi-hit PIK3CA mutations amplify PI3K⍺ signaling more than single-point mutations, suggesting heightened sensitivity to PI3K⍺ inhibitors.

Purpose of the Study:

  • To determine the prevalence of PIK3CA multi-hit mutations in metastatic CRC.
  • To identify patients who could potentially benefit from PI3K inhibitors based on PIK3CA mutation status.

Main Methods:

  • Analysis of the Foundation Medicine database for CRC patients who underwent genomic profiling between 2013 and 2021.
  • Abstraction of molecular and clinical variables for patients with PIK3CA mutations.

Main Results:

  • 1.7% (710/41154) of CRC patients had multi-hit PIK3CA mutations.
  • Microsatellite instability-high status was observed in 17.6% of these patients.
  • Common PIK3CA variants included H1047R, E545K, and E542K, with E542K-E545K being the most frequent pair.

Conclusions:

  • Multi-hit PIK3CA mutations represent a significant subset (1.7%) of advanced CRC.
  • These patients may exhibit increased sensitivity to PI3K inhibitors.
  • Further research is warranted to explore the clinical utility of PI3K inhibitors in this specific CRC population.
Keywords:
PIK3CA oncogenePI3K inhibitorcolorectal cancermutations

More Related Videos

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

13.6K
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

24.3K

Related Concept Videos

Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.2K
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...
3.4K
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
11.8K
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...
3.8K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.3K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.7K