Cancer has been the leading cause of death for 42 consecutive years. Research indicates that around 30% of common cancers such as lung, liver, and breast cancer exhibit MYC gene amplification or expression variations, leading to rapid cancer cell growth and high postoperative recurrence rates, thus lowering overall patient survival rates. The National Health Research Institutes (NHRI) has identified a new targeted drug that promotes the degradation of the MYC cancer-driving protein, which can significantly benefit cancer treatment by preventing protein dysregulation.
Huey-Kang Sytwu, President of NHRI, highlighted that the global incidence of cancer is rapidly increasing. According to the American Association for Cancer Research, in 2020, approximately 18.1 million people worldwide were diagnosed with cancer, and 9.8 million died from it, with a mortality rate exceeding 50%. It is estimated that by 2040, the number of global cancer cases will reach 28 million, with about 16.2 million deaths.
Despite global efforts in developing cancer treatment technologies and new drugs, the mutation of cancer cells can render these treatments ineffective. While many targeted therapies address specific genetic mutations in cancer cells, there are currently no targeted treatments for the MYC and MYCN cancer genes.
Ya-Hui Chi, a researcher at NHRI's Institute of Biotechnology and Pharmaceutical Research (IBPR), explained that cancer cells rely on glycolysis to obtain more energy and materials needed for rapid growth compared to normal cells. The MYC protein functions as a transcription factor that aids in producing numerous cells and the enzymes necessary for glycolysis. About 28% of common cancers, including lung, liver, breast, lymphoma, prostate, and endometrial cancers, have MYC oncogene amplification.
To effectively starve cancer cells, it is crucial to block the expression of the MYC oncogene. Although scientists understand this mechanism, the structure of the MYC protein remains unsolved, making it difficult to design small molecule compounds to inhibit gene amplification.
The NHRI team leveraged the characteristic of Aurora kinase A stabilizing the MYC protein to design small molecule compounds that disrupt the binding between the two proteins. This leads to the degradation of MYC protein in the proteasome within cells. They discovered the candidate drug DBPR728, an orally administered small molecule kinase inhibitor, which promotes the degradation of the MYC cancer-driving protein within tumors, inhibiting glycolysis and inducing cancer cell apoptosis.
In various mouse xenograft tumor models with MYC gene amplification or high expression, such as small cell lung cancer, triple-negative breast cancer, liver cancer, and medulloblastoma, DBPR728 has been shown to cause tumor regression. In some cases, no recurrence was observed within three months after stopping the treatment.
Resource (mandarin): 近3成癌症帶有MYC基因 國衛院找出新藥 讓癌細胞凋亡
