CRISPRing KRAS: A Winding Road with a Bright Future in Basic and Translational Cancer Research

Xian Gong1,2, Jianting Du1,2, Ren-Wang Peng3

  • 1Department of Thoracic Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China.

Cancers
|January 26, 2024
PubMed

Insights

CRISPR gene editing offers new hope for KRAS-mutant cancers, previously untreatable due to RAS protein binding challenges. This review explores CRISPR

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Editing Technology

Background:

  • KRAS-mutant tumors have been historically "undruggable" due to RAS proteins' high affinity for GTP and lack of suitable drug-binding pockets.
  • Developing targeted therapies for these cancers remains a significant research challenge.
  • CRISPR technology is emerging as a powerful tool in cancer research.

Purpose of the Study:

  • To provide a comprehensive review of CRISPR system applications in KRAS-mutant cancer research.
  • To summarize recent advances in understanding KRAS biology and drug resistance mechanisms.
  • To highlight CRISPR's role in exploring anti-tumor immunity, epigenetic regulation, and synthetic lethality in KRAS-mutant cancers.

Main Methods:

  • Review of existing literature on CRISPR technology and KRAS-mutant cancer research.
  • Synthesis of recent findings on KRAS biology, drug resistance, and immune response.
  • Analysis of CRISPR's utility in investigating epigenetic networks and synthetic lethality.

Main Results:

  • CRISPR is increasingly utilized in basic and translational research for KRAS-mutant cancers.
  • Advances have been made in understanding the mechanistic basis of KRAS biology and drug resistance.
  • CRISPR facilitates exploration of anti-tumor immunity, epigenetic regulation, and synthetic lethality pathways.

Conclusions:

  • CRISPR technology is a valuable tool for advancing research in KRAS-mutant cancers.
  • This review consolidates current knowledge and future directions for CRISPR-based therapeutic strategies.
  • Further research utilizing CRISPR holds promise for overcoming challenges in treating KRAS-mutant tumors.

Related Concept Videos

CRISPR and crRNAs02:53

CRISPR and crRNAs

Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
17.0K
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
50.5K
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...
6.2K
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...
3.8K
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...
5.5K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.9K