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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 specific...

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Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.

Kaibo Guo1,2, Yuqian Feng3, Jiamin Lu4

  • 1Department of Oncology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China.

Cancer Science
|May 28, 2026
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Summary

Pyroptosis, a programmed cell death, has a dual role in colorectal cancer (CRC). While inflammation can promote tumors, inducing pyroptosis offers antitumor effects and enhances cancer therapies.

Keywords:
colorectal cancer immunotherapygasdermin familyinflammasome activationpyroptosistumor microenvironment remodeling

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Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Pyroptosis, a programmed cell death pathway, is mediated by gasdermin proteins and plays a complex role in colorectal cancer (CRC).
  • Chronic inflammation driven by pyroptosis can promote CRC tumorigenesis.
  • Acute pyroptosis induction in tumor cells shows potential for antitumor effects.

Purpose of the Study:

  • To elucidate the multifaceted roles of pyroptosis and its mediators, gasdermin proteins and inflammasomes, in colorectal cancer.
  • To explore the therapeutic implications of targeting pyroptosis in CRC treatment.
  • To understand the interplay between pyroptosis, the tumor microenvironment, and gut microbiota in CRC.

Main Methods:

  • Analysis of gasdermin protein functions (GSDMD, GSDME, GSDMC) in CRC progression and therapy.
  • Investigation of inflammasome pathways (NLRP3, AIM2) and their impact on CRC pathogenesis.
  • Examination of the influence of gut microbiota on pyroptosis and CRC outcomes.
  • Review of therapeutic strategies involving pyroptosis induction in combination with conventional and immunotherapies.

Main Results:

  • Gasdermin proteins exhibit isoform-specific roles; GSDMD activation can induce pyroptosis and modulate immune infiltration, while GSDMC may promote CRC progression.
  • GSDME expression enhances sensitivity to chemoradiation and synergizes with immune checkpoint inhibitors.
  • NLRP3 inflammasome activation can exacerbate CRC growth, whereas AIM2 shows tumor-suppressive effects, particularly in BRAF-mutant CRC.
  • Gut microbiota composition affects chemoresistance and antitumor immunity.
  • Pyroptosis induction synergizes with existing therapies, overcoming apoptosis resistance and remodeling the tumor microenvironment by releasing tumor antigens and DAMPs.

Conclusions:

  • Pyroptosis presents a double-edged sword in colorectal cancer, with potential for both promoting and combating the disease.
  • Targeting pyroptosis, particularly through GSDME, offers promising therapeutic avenues for CRC, enhancing responses to conventional treatments and immunotherapies.
  • Future research should focus on isoform-specific gasdermin functions and optimizing pyroptosis-inducing therapeutic strategies for CRC.