Related Experiment Video

Updated: Apr 28, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

2.4K

Small-molecule modulation of Ras signaling

Jochen Spiegel1, Philipp M Cromm1, Gunther Zimmermann1

  • 11] Max Planck Institute of Molecular Physiology, Dortmund, Germany. [2] Department of Chemistry and Chemical Biology, Technical University Dortmund, Dortmund, Germany.

Nature Chemical Biology
|June 16, 2014
PubMed

Insights

Targeting mutated Ras proteins, particularly K-Ras, is a significant challenge in cancer therapy. Recent discoveries enable direct targeting of K-Ras(G12C) and Ras chaperone PDEδ, offering new hope for effective cancer drugs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Oncogenic Ras proteins, especially K-Ras, are implicated in 20-30% of human cancers and are notoriously difficult to target therapeutically.
  • K-Ras is a key 'undruggable' target in cancer research due to its role in numerous malignancies unresponsive to current treatments.

Purpose of the Study:

  • To review recent advances in targeting oncogenic Ras proteins for cancer therapy.
  • To highlight novel strategies for developing new anti-cancer drugs targeting Ras.

Main Methods:

  • Identification of new small-molecule ligand-binding cavities on Ras.
  • Development of selective direct targeting strategies for mutated K-Ras(G12C).
  • Exploration of targeting the prenyl-binding Ras chaperone PDEδ to impair Ras spatial organization.

Main Results:

  • Selective direct targeting of mutated K-Ras(G12C) has become feasible.
  • Targeting PDEδ offers a new approach to disrupt Ras function and organization.
  • These advancements present a fresh perspective for anticancer drug development.

Conclusions:

  • Recent breakthroughs provide the first opportunities for the direct and selective targeting of mutated K-Ras.
  • Targeting Ras chaperones like PDEδ represents a promising new avenue in cancer research.
  • These developments significantly enhance the prospects for novel Ras-targeted cancer therapeutics.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

5.7K
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

10.3K

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...
5.7K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.4K
The Ras Gene02:38

The Ras Gene

2.3K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.3K
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...
4.7K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
15.2K