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Related Concept Videos

The Ras Gene02:38

The Ras Gene

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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...
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The Ras Gene02:38

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Small GTPases - Ras and Rho01:24

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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.
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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.
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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...
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Rab Proteins01:14

Rab Proteins

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Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
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Acquisition of resistance to RAS inhibition is associated with the upregulation of macropinocytosis through both PI3K-dependent and -independent signaling.

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Related Experiment Video

Updated: Apr 22, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
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Drugging the undruggable RAS: Mission possible?

Adrienne D Cox1, Stephen W Fesik2, Alec C Kimmelman3

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

Nature Reviews. Drug Discovery
|October 18, 2014
PubMed
Summary

Targeting RAS oncoproteins, long considered undruggable, shows renewed promise. This review explores five key strategies, including direct inhibition and targeting downstream effectors, offering new hope for cancer therapy.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • RAS oncoproteins have been a persistent challenge in cancer therapy for over 30 years.
  • The perception of RAS proteins as 'undruggable' has limited therapeutic development.
  • Recent advancements offer new hope for developing effective RAS-inhibitory molecules.

Purpose of the Study:

  • To review the progress and potential of five key therapeutic approaches targeting RAS.
  • To assess the viability of direct RAS inhibition, membrane association blocking, and downstream effector targeting.
  • To explore synthetic lethality and metabolic exploitation for mutant RAS therapies.

Main Methods:

  • Review of current scientific literature and clinical data on RAS-targeting strategies.
  • Analysis of five distinct therapeutic avenues: direct inhibition, membrane association, downstream signaling, synthetic lethality, and metabolic pathways.
  • Discussion of the complexities and future perspectives for each approach.

Main Results:

  • Direct RAS inhibition and blocking membrane association are areas of active investigation.
  • Targeting RAS downstream effector signaling is currently the most promising approach.
  • Exploiting synthetic lethal interactors and RAS-mediated metabolic changes presents novel therapeutic opportunities.

Conclusions:

  • Despite historical challenges, multiple strategies show promise for targeting RAS oncoproteins.
  • Targeting downstream effectors and exploring metabolic vulnerabilities offer significant therapeutic potential.
  • Further research is needed to overcome complexities and fully realize the potential of these RAS-targeting approaches.