Related Experiment Video

Updated: Oct 25, 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

11.3K

A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies

Zhiwei Liu1, Yingluo Liu1, Lili Qian2

  • 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China.

Molecular Cell
|August 10, 2021
PubMed

Insights

This study maps KRAS mutant cancers, revealing three distinct subtypes. A combination of DOT1L and SHP2 inhibitors shows promise for treating a subset with poor prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Proteomics

Background:

  • KRAS-mutant cancers present therapeutic challenges due to complex phosphorylation signaling.
  • A comprehensive proteomic and phosphoproteomic profile of these cancers is currently lacking.

Purpose of the Study:

  • To create a proteomic and phosphoproteomic landscape of KRAS-mutant cancer cell lines.
  • To identify distinct cancer subsets and potential therapeutic strategies through integrative analysis.

Main Methods:

  • Proteomic and phosphoproteomic profiling of 43 KRAS-mutant cancer cell lines.
  • Integration of transcriptomics, proteomics, and phosphoproteomics data.
  • Analysis of drug sensitivity in relation to phosphoproteome data.

Main Results:

  • Identification of three distinct subsets of KRAS-mutant cancers with unique characteristics.
  • Discovery of potential drug combinations by integrating phosphoproteome and drug sensitivity data.
  • Validation of DOT1L and SHP2 inhibitor combination therapy for a specific subset (subset 2) linked to poor prognosis.

Conclusions:

  • This study provides a valuable resource for understanding KRAS-mutant cancer heterogeneity.
  • The identified DOT1L and SHP2 inhibitor combination offers a targeted therapeutic strategy for a subset of KRAS-mutant cancers.
  • Findings pave the way for developing novel therapeutic approaches for challenging KRAS-driven malignancies.
Keywords:
DOT1LKRAS mutationSHP2cancerdrug sensitivityheterogeneityphosphoproteomicsproteomicssubtypetherapy

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

18.2K
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

8.1K

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.3K
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...
4.0K
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...
6.6K
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...
8.0K
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...
4.7K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.7K