Related Experiment Video

Updated: Sep 2, 2025

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

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

Published on: December 9, 2015

10.7K

Targeting KRAS mutant cancers: from druggable therapy to drug resistance

Chunxiao Zhu1,2, Xiaoqing Guan1,3, Xinuo Zhang1,4

  • 1The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310022, China.

Molecular Cancer
|August 3, 2022
PubMed

Insights

Targeting Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutations is now possible with new inhibitors. This review covers advances in KRAS-targeted therapies, resistance mechanisms, and combination strategies for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is the most frequently mutated oncogene across various cancers.
  • KRAS mutations were historically considered undruggable due to the lack of suitable drug binding sites.
  • Previous efforts focused on indirect targeting of KRAS-mutant cancers via expression, regulators, or effectors.

Purpose of the Study:

  • To review recent therapeutic advances targeting KRAS mutations.
  • To discuss emerging mechanisms of drug resistance to KRAS inhibitors.
  • To explore opportunities for combination therapies in KRAS-mutant cancers.

Main Methods:

  • Literature review of recent scientific publications on KRAS-targeted therapies.
  • Analysis of clinical responses and resistance mechanisms associated with KRAS inhibitors.
  • Synthesis of information on current and future therapeutic strategies.

Main Results:

  • The development of KRAS (G12C) inhibitors has made KRAS mutations druggable, showing clinical responses.
  • Resistance to KRAS inhibitor monotherapy is a significant clinical challenge.
  • Substantial progress has been made in understanding the molecular mechanisms underlying drug resistance.

Conclusions:

  • KRAS inhibitors represent a breakthrough in treating KRAS-mutant cancers.
  • Understanding and overcoming resistance mechanisms is crucial for sustained therapeutic efficacy.
  • Combination therapies hold promise for improving outcomes in KRAS-mutant cancers.
Keywords:
Combination therapyDruggableKRAS mutationsResistance

More Related Videos

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

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

7.3K
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.0K

Related Concept Videos

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...
7.8K
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
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...
5.1K
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...
6.4K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
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