Cutting off the nutrient supply essential for cancer cell growth— National Health Research Institutes Discovers New Targeted Therapy Drug that Promotes Degradation of MYC Oncoproteins
- Date: 2024-08-05
- Update: 2024-08-05
- Source: 國家衛生研究院
- Views: 218
Cutting off the nutrient supply essential for cancer cell growth—
National Health Research Institutes Discovers New Targeted Therapy Drug that Promotes Degradation of MYC Oncoproteins
The occurrence of cancer is frequently linked to genetic variations that lead to uncontrolled cell proliferation. Oncogenes are gene variants that can transform normal cells into cancerous ones. These variations may result from gene mutation or amplification. Many targeted therapies available on the market, such as “Glivec” for chronic myeloid leukemia and “Iressa” for lung adenocarcinoma, have been developed to address specific genetic variations in cancer cells. However, despite being identified in clinical and academic research for many years, several oncogenes and their resulting cancer-driving proteins, such as the MYC oncogene, remain challenging to develop into drugs due to the intrinsic properties of the proteins.
Approximately 28% of cancers exhibit MYC gene amplification. The MYC oncoprotein functions as a transcription factor, facilitating the production of enzymes required for glycolysis. Tumors with MYC overexpression can fully utilize glycolysis, allowing cancer cells to metabolize energy in low-oxygen conditions, leading to uncontrolled cell growth and high postoperative recurrence rates, ultimately reducing overall patient survival rates.
Scientists from the Institute of Biotechnology and Pharmaceutical Research at the National Health Research Institutes, including Ya-Hui Chi, Teng-Kuang Yeh, Chiung-Tong Chen, and Chun-Ping Chang, have discovered a novel orally available small molecule, DBPR728, that can promote the degradation of MYC oncoproteins within tumors. By exploiting Aurora kinase A’s property of stabilizing the MYC protein, the team designed small molecules that disrupt the interaction between the two proteins, leading to MYC protein degradation. They demonstrated that DBPR728 effectively suppressed glycolysis, leading to regression of xenograft tumors with MYC gene amplification or overexpression, including small cell lung cancer, triple-negative breast cancer, liver cancer, and medulloblastoma. These findings were published in the June 2024 issue of Molecular Cancer Therapeutics, a leading journal published by the American Association for Cancer Research, and the paper was highlighted as the cover article.
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