The Cause of Colon Cancer Recurrence... The Two Faces of p53

Using Organoids Reproducing Cancer Patient-Specific Bioactivity
Proposing a Recurrence Suppression Strategy After Colorectal Cancer Chemotherapy (5-FU)

Functional Duality of p53 After Treatment with 5-FU-Based Chemotherapeutic Agents

[Asia Economy Reporter Junho Hwang] A study has revealed that p53, a representative tumor suppressor in our body, paradoxically aids the activation of cancer stem cells, thereby facilitating the recurrence of colorectal cancer. This finding is expected to contribute to improving survival rates after 5-fluorouracil (5-FU)-based combination therapy, which is used in the treatment of various cancers including colorectal cancer. The Korea Research Foundation announced on the 4th that a research team led by Professor Kang-Yeol Choi of Yonsei University published these findings in the international journal Nature Communications.

Uncovering the Cause of Cancer Recurrence After Standard Chemotherapy

Mechanism of Recurrence Through Activation of Cancer Stem Cells After 5-FU-Based Chemotherapy

The research team succeeded in elucidating the molecular mechanism related to cancer recurrence following the standard chemotherapy regimen for colorectal cancer, the '5-FU-based combination therapy.' The study found that p53, known as a representative tumor suppressor, paradoxically aids the activation of cancer stem cells, inducing cancer recurrence.

The team examined the activation of cancer stem cells after combination therapy using organoids cultured from colorectal cancer patients' cancer cells and a colorectal cancer mouse model. Organoids are organ mimetics created by culturing stem cells to replicate the structure and function of specific organs. The team collaborated with Professor Hans Clevers' research group at the Hubrecht Institute in the Netherlands, who first developed intestinal organoids by culturing intestinal stem cells, and secured organoids derived from intestinal cells lacking p53.

Through this, the team identified that p53 plays a different role in the cancer recurrence process than previously understood. p53 is known as a tumor suppressor that monitors the cell's condition for DNA damage or abnormal growth signals. However, the team confirmed that during cancer recurrence, p53 stimulates the WNT signaling pathway, which plays a signaling role in cancer initiation and progression, thereby activating cancer stem cells.

Preventing Cancer Recurrence After Anticancer Treatment

Inhibition of Cancer Cell Regrowth After 5-FU Treatment Discontinuation Using WNT Inhibitors

Additionally, the research team treated organoids derived from actual patient cancer cells and animal models implanted with colorectal cancer cells with a chemical that inhibits the WNT signaling pathway. As a result, they confirmed that the activation of cancer stem cells induced by 5-fluorouracil was suppressed, and tumor regrowth occurring after single treatment was inhibited.

The team stated, "'This study supports the need for combination therapy with WNT signaling inhibitors to maximize drug efficacy and suppress recurrence during 5-FU-based combination therapy,' and added, 'We expect this to greatly contribute to solving the problem of patient deaths caused by frequent cancer recurrence after 5-FU-based combination treatment.'

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