Related Experiment Video

Updated: Oct 13, 2025

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells
09:20

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells

Published on: July 6, 2021

2.5K

KRAS mutation: from undruggable to druggable in cancer

Lamei Huang1, Zhixing Guo1, Fang Wang1

  • 1State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Esophageal Cancer Institute, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China.

Signal Transduction and Targeted Therapy
|November 15, 2021
PubMed

Insights

Targeting Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations, especially KRAS (G12C), has shown promise in cancer treatment. Recent advances include approved KRAS (G12C) inhibitors, offering new hope for precise cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Cancer remains a leading cause of death globally, with targeted therapies revolutionizing treatment outcomes.
  • Kirsten rat sarcoma viral oncogene homologue (KRAS) is the most frequently mutated oncogene, playing a critical role in cancer initiation and progression.
  • Despite extensive efforts, KRAS has historically been a challenging, often considered
  • undruggable
  • therapeutic target.

Purpose of the Study:

  • To review the fundamental aspects of KRAS and its mutations in cancer.
  • To explore the link between KRAS mutations and tumor immune evasion.
  • To summarize recent advancements in targeting KRAS, particularly the KRAS (G12C) mutation, including novel inhibitors and combination therapies.

Main Methods:

  • Literature review of recent studies on KRAS.
  • Analysis of clinical trial data for KRAS (G12C) inhibitors.
  • Discussion of resistance mechanisms and combination treatment strategies.

Main Results:

  • Significant progress has been made in developing direct KRAS (G12C) inhibitors like sotorasib (AMG510) and adagrasib (MRTX849).
  • Sotorasib (AMG510) is the first KRAS (G12C)-targeted drug approved for clinical use, demonstrating encouraging clinical trial results.
  • KRAS mutations are implicated in tumor immune evasion, highlighting potential for immunotherapy combinations.

Conclusions:

  • Targeting KRAS (G12C) represents a breakthrough in precision oncology.
  • Understanding resistance mechanisms is crucial for optimizing treatment with KRAS (G12C) inhibitors.
  • Combination therapies hold promise for improving patient outcomes and achieving personalized cancer treatment.

More Related Videos

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

10.7K
Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics12:28

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics

Published on: January 11, 2019

7.5K

Related Concept Videos

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...
3.4K
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...
6.5K
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
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...
3.9K
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...
7.9K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.8K