A team of Indian scientists has developed a new method to study and potentially treat signet ring cell carcinoma (SRCC), a rare and aggressive form of colorectal cancer (CRC).

About CRC and SRCC

• Colorectal cancer (CRC) is a type of cancer that begins in the colon or rectum, parts of the large intestine in the digestive system.
  • It is the third most common cancer worldwide and second leading cause of cancer-related deaths globally.
• Understanding SRCC: Signet Ring Cell Carcinoma (SRCC) is a rare and deadly subtype of CRC, constituting about 1% of global CRC cases.
  • The name “signet ring” comes from the distinct ring-like appearance of cancer cells when viewed under a microscope.
  • It is often diagnosed at an advanced stage and resists traditional chemotherapy.
• SRCC in India: In India, SRCC appears to affect a significantly higher number of patients, nearly ten times more than the global average.
  • It frequently impacts younger individuals and is more common in central and northern India.

Challenges in Diagnosing and Treating SRCC

• Aggressive Nature of the Disease: It spreads rapidly and often metastasizes to the peritoneum, the lining of the abdominal cavity.
  • This peritoneal spread is a key reason for the poor prognosis and difficulty in treatment.
• Lack of Effective Treatment Options: SRCC typically does not respond to standard chemotherapy regimens.
  • The absence of suitable preclinical models has made targeted research and drug testing difficult until now.

Significance of the Study on SRCC

• Development of New Models: The researchers have developed Patient-Derived Organoids (PDOs) and Patient-Derived Xenografts (PDXs).
  • PDOs are miniature lab-grown tumors from real patient samples, while PDXs are tumor implants in mice that mimic actual human cancer behavior.
• Advantages of PDOs and PDXs: These models closely replicate the molecular behavior of human SRCC tumors. They allow scientists to study cancer in a controlled environment and identify how it responds to different treatments.
• Creation of a Living Biobank: The project has led to the formation of one of the first living biobanks of SRCC models in the world.
  • This biobank is a valuable resource for future drug testing and personalized treatment development.
• Understanding SRCC’s Resistance: The study uncovered unique molecular features that explain why SRCC does not respond to standard chemotherapy.
  • These insights reveal specific vulnerabilities that can be targeted with customized therapies.
• Promising Drug Combinations: A novel three-drug combination tested on the lab models was found to shrink tumors and limit cancer spread showing potential for new treatment strategies and may lead to clinical trials in the future.

Conclusion

• This research marks a major step forward in the understanding and treatment of SRCC.
• The newly developed models provide a scientific foundation for targeted therapies, offering hope to patients suffering from this rare and aggressive cancer subtype.
• Phase 1 clinical trials will be necessary to determine the safety and effectiveness of the new treatment combinations in humans.

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