National Health Research Institutes

Drug resistance in cancer chemotherapy poses a major clinical challenge, particularly for patients with triple-negative breast cancer (TNBC)—a deadly subtype accounting for 10–15% of all breast cancers. Due to the lack of hormone receptors and HER2 expression, TNBC cannot be treated with current targeted therapies; instead, the current treatment relies solely on traditional chemotherapeutics such as paclitaxel. Although the current approach is initially effective, more than 40% of patients experience recurrence, with TNBC relapse occurring three times more frequently than other breast cancers, most commonly within three years of diagnosis. Recurrent tumors often acquire resistance to multiple drugs, leaving patients with limited or no treatment options.

KIF2C: the “Mitotic Inspector” Key to Overcoming Drug Resistance

To tackle this issue, Professor Lily Hui-Ching Wang and Distinguished Chair Professor Yu-Ju Sun of the College of Life Sciences at National Tsing Hua University (NTHU) began a collaborative effort in 2017. Using clinical big data and molecular tools, they identified a novel therapeutic target to combat chemoresistance in TNBC: the kinesin family protein KIF2C. KIF2C is a microtubule depolymerase that corrects improper chromosome-microtubule attachments, ensuring accurate chromosome segregation and genomic stability. Professor Wang explained that KIF2C is a “mitotic inspector” that oversees the correct assembly of spindles. However, when overexpressed in cancer cells, KIF2C enables cells to divide normally despite paclitaxel treatment, contributing to drug resistance.

World’s First-in-class KIF2C Small-molecule Inhibitor Developed

Dr. Hsing-Pang Hsieh, who is both the director of the National Health Research Institutes’ Institute of Biotechnology and Pharmaceutical Research and a professor at NTHU’s Department of Chemistry, supervised the synthesis of over 60 KIF2C inhibitors by a PhD and MSc student. Collaborating with professors Wang and Sun and NHRI researchers Dr. Ching-Chuan Kuo and Dr. Shu-Yu Lin, the team successfully developed the first cell-permeable KIF2C-specific small-molecule inhibitor, BPRMC007S9 (7S9).

Outstanding Research Collaboration Drives Translational Innovation

Dr. Hsieh emphasized that the success of this globally leading research lies in interdisciplinary collaboration. Professor Wang served as the project lead, while Professor Sun contributed structural analyses of KIF2C to guide drug design, Dr. Kuo conducted in vivo efficacy tests, and Dr. Lin, who began her participation in the project during her postdoctoral training, is now working on developing KIF2C degraders as next-generation therapies.

From Bench to Bedside: Academic Innovation Translates to Clinical Impact

The research team, advised by Professors Wang and Hsieh, formed a startup team—Beliminate Biomedical—led by PhD student and first author Yuan-Shao Pao. In 2024, the team won the Gold Award in the Smart Health Category at the National Intercollegiate Innovation and Entrepreneurship Competition; it also joined the 17th NTHU Startup Garage and was invited to present at InnoVEX 2025. With support from the National Science and Technology Council’s 2025 Taiwan Germination Program, the team is advancing preclinical development of the KIF2C inhibitor toward clinical trials.

A Model of Scientific Perseverance

NHRI President Huey-Kang Sytwu recalled that early struggles with limited funding nearly halted the team’s research. With support from NHRI’s competitive incubation programs and NTHU’s seed funding initiatives, the team persevered and ultimately succeeded through a three-year integrated medical research program. The publication in Developmental Cell signifies not only a milestone for understanding of the KIF2C inhibitor but also a successful model of inter-institutional cooperation. President Sytwu concluded by expressing his hope that the drug will soon reach clinical trials and bring new hope to cancer patients who currently have no effective treatment options.