Chung Times reporters Lin Chou-Yi and Chen Chun-Chi

Breast cancer is the most common cancer among women, and triple-negative breast cancer (TNBC) accounts for about 10–15% of all breast cancer cases. Due to the lack of hormone receptors and HER2 protein expression, TNBC cannot be treated with targeted therapies and relies solely on traditional chemotherapy agents such as paclitaxel. The recurrence rate of TNBC is three times higher than that of other types of breast cancer, and once recurrence occurs, drug resistance often renders further treatment ineffective.

A team from the National Health Research Institutes (NHRI) and National Tsing Hua University (NTHU) has successfully developed the world’s first cell-penetrating small molecule inhibitor targeting KIF2C, a protein responsible for cancer cell division, marking a significant breakthrough in next-generation anti-cancer drug development.

Among TNBC patients, about 30–40% experience recurrence within five years. Recurrent tumors often develop multidrug resistance, leaving patients without viable treatment options. The five-year survival rate drops from 77% to as low as 8–12% after recurrence, highlighting the urgent need for new targeted therapies capable of overcoming drug resistance.

Since 2017, a research team led by Professor Hui-Ching Wang and Chair Professor Yu-Ju Sun from NTHU’s College of Life Science has used clinical big data and molecular techniques to identify a new therapeutic target—kinesin family member 2C (KIF2C)—for overcoming chemotherapy resistance in TNBC. KIF2C is a microtubule-depolymerizing protein responsible for correcting erroneous chromosomal attachments and ensuring accurate chromosome segregation, thereby maintaining genomic stability.

Professor Wang explained that KIF2C acts like a "traffic warden" for cell division, correcting faulty microtubule connections. However, in cancer cells, overexpression of KIF2C helps tumors resist the effects of paclitaxel by ensuring successful cell division even under chemotherapy stress, thereby contributing to drug resistance. Drug-resistant tumors often enhance KIF2C activity through post-translational modifications of tubulin, making KIF2C inhibition a promising strategy to overcome resistance.

Dr. Hsing-Pang Hsieh, Director of the NHRI Institute of Biotechnology and Pharmaceutical Research and jointly appointed professor at NTHU’s Department of Chemistry, led students in synthesizing over 60 different KIF2C inhibitors. Through cross-institutional collaboration, the team developed the world’s first cell-permeable small molecule KIF2C inhibitor. Their findings will be published in August in Developmental Cell, the top-ranked journal in developmental biology.

The research team has extended the application of the KIF2C inhibitor from TNBC to other major gynecological cancers such as ovarian and endometrial cancers. NHRI President Huey-Kang Sytwu noted that the team initially struggled with limited funding and nearly failed to launch the project. Fortunately, support from NHRI’s competitive incubation program and NTHU’s emerging teams and seed funding programs enabled the research to continue and ultimately succeed.

This achievement demonstrates Taiwan’s international competitiveness in biomedical research. The team hopes the KIF2C inhibitor will soon enter clinical trials and bring new hope to patients with drug-resistant cancers.