Related Experiment Video

Updated: May 22, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

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

Published on: September 30, 2016

Common PIK3CA mutants and a novel 3' UTR mutation are associated with increased sensitivity to saracatinib

John J Arcaroli1, Kevin S Quackenbush, Rebecca W Powell

  • 1Division of Medical Oncology, University of Colorado Denver and University of Colorado Cancer Center, Denver, Colorado 80045, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 4, 2012
PubMed
Abstract

Insights

Targeting Src in PIK3CA-mutant colorectal cancer patients with saracatinib shows promise. Specific PIK3CA mutations correlate with increased sensitivity, suggesting a personalized treatment approach for this subset.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Dysregulation of phosphoinositide 3-kinase (PI3K) and Src signaling pathways is common in colorectal cancer.
  • PIK3CA gene mutations are linked to increased disease severity and poorer clinical outcomes.
  • Elevated Src levels in premalignant lesions suggest a role in colorectal cancer progression.

Purpose of the Study:

  • To investigate the efficacy of saracatinib in colorectal cancer.
  • To determine the association between PIK3CA mutations and sensitivity to saracatinib.
  • To explore the impact of Src inhibition on Akt-dependent signaling.

Main Methods:

  • Utilized colorectal cancer cell lines and patient-derived explant models.
  • Evaluated PIK3CA mutations (exon 9 and 20) for correlation with saracatinib sensitivity.
  • Assessed the effect of Src inhibition on Src-p85 interaction and Akt signaling.

Main Results:

  • Identified a subset of patients with PIK3CA mutations (exon 9 and 20) exhibiting increased sensitivity to saracatinib.
  • Discovered a novel 3' untranslated region (UTR) mutation associated with saracatinib sensitivity and reduced affinity for miR-520a/miR-525a.
  • Demonstrated that Src inhibition decreases Src-p85 interaction, leading to reduced Akt-dependent signaling.

Conclusions:

  • Saracatinib shows potential as a targeted therapy for a subset of colorectal cancer patients with PIK3CA mutations.
  • A personalized approach targeting Src in PIK3CA-mutant colorectal cancers may be effective.
  • Further research into the specific genetic alterations and their impact on therapeutic response is warranted.

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
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...