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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...
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:
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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...
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...
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...

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Related Experiment Video

Updated: May 8, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

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

Published on: July 17, 2019

Disrupted molecular glue complex drives RAS inhibitor resistance.

Ben Sang1, Ling Feng Ye2, Zheng Fu1

  • 1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Cell
|May 7, 2026
PubMed
Summary
This summary is machine-generated.

Tri-complex inhibitors (TCIs) show promise in RAS-mutant cancers, but resistance emerges. New research identifies specific RAS and BRAF mutations causing resistance and suggests targeted therapies to overcome them, improving cancer treatment strategies.

Keywords:
RAFRASRAS inhibitoracquired resistancecancerclinical resistancedaraxonrasibmolecular gluestargeted therapytri-complex inhibitor

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Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells
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Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

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Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

Related Experiment Videos

Last Updated: May 8, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

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

Published on: July 17, 2019

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells
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Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

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Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Tri-complex inhibitors (TCIs) are molecular glues targeting the GTP-bound RAS state.
  • TCIs recruit cyclophilin A (CYPA) to form a complex, inhibiting oncogenic signaling.
  • Clinical activity of TCIs in RAS-mutant cancers is observed, but resistance mechanisms are not well understood.

Purpose of the Study:

  • To investigate resistance mechanisms to the RAS inhibitor daraxonrasib in patients with RAS-mutant cancers.
  • To identify specific genetic alterations conferring resistance to TCIs.
  • To develop strategies to overcome TCI resistance.

Main Methods:

  • Analysis of paired patient samples (baseline and end-of-treatment) from 40 patients treated with daraxonrasib.
  • Structural and functional analyses of identified mutations.
  • Identification of novel TCIs and combination therapies.

Main Results:

  • Recurrent resistance alterations were identified in 18 out of 40 patients.
  • Mutations in RAS (Y64) disrupted inhibitor binding.
  • Mutations in RAS (Y71) or BRAF (kinase-dead) enhanced RAS-RAF signaling, conferring resistance.
  • A TCI targeting RAS Y64 mutants was identified.
  • Combination therapies for kinase-dead BRAF-driven resistance were proposed.

Conclusions:

  • Convergent resistance mechanisms undermine TCI efficacy by disrupting molecular glue function.
  • Targeting specific RAS and BRAF mutations is crucial for overcoming resistance.
  • The findings provide a blueprint for enhancing therapeutic strategies in RAS-driven malignancies.