Taiwan Researchers Target Chemotherapy Resistance in Triple-Negative Breast Cancer

A new drug candidate targets a difficult treatment problem

Researchers at Taiwan's National Health Research Institutes (NHRI) and National Tsing Hua University (NTHU) announced on July 4, 2025, that they had developed a drug candidate targeting KIF2C, a protein linked to chemotherapy resistance in triple-negative breast cancer. The treatment is undergoing preclinical testing, with the aim of helping a common chemotherapy drug, paclitaxel, work against cancer cells that have become resistant to it.

The team, led by Professor Lily Hui-ching Wang and Dr. Hsieh Hsing-pang, describes the candidate as the world's first cell-penetrating small-molecule inhibitor specifically targeting KIF2C. In laboratory studies, combining the candidate with paclitaxel was more effective than using either treatment alone.

Triple-negative breast cancer, often shortened to TNBC, accounts for about 10% to 20% of breast cancer cases worldwide. It is an aggressive form of the disease with fewer treatment options than breast cancers that respond to hormone medicines or drugs targeting the HER2 protein. For patients whose cancer returns and resists chemotherapy, those options become narrower still.

The Taiwanese research focuses on that resistance problem. The candidate enters cells and blocks a protein involved in cell division, making cancer cells more susceptible to chemotherapy. The researchers have also applied the approach to ovarian, endometrial and cervical cancers, suggesting possible uses beyond breast cancer.

As of July 5, 2025, the work remains at the stage of testing before human clinical trials. The project has support from Taiwan's National Science and Technology Council, and the team hopes a successful development process could bring the treatment to market within five years. Human testing, regulatory review and arrangements for patient access still lie ahead.

Why triple-negative breast cancer is harder to treat

Triple-negative breast cancer gets its name from the absence of three targets commonly used to guide breast cancer treatment: the estrogen receptor (ER), the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Receptors are proteins that receive signals affecting how cells behave. Medicines can act on these targets when they are present.

TNBC lacks the hormone receptors and HER2 target that make hormone therapies and drugs directed at HER2 effective in other breast cancer subtypes. Chemotherapy has therefore remained the main treatment, using medicines that attack cancer cells rather than relying on those three targets.

The disease is associated with aggressive growth, a greater likelihood of recurrence and a poorer prognosis than other forms of breast cancer. The figures cited for TNBC include a survival rate over five years of around 77% and a recurrence rate of 30% to 40%. When the disease returns, resistance to drugs such as paclitaxel can become a major treatment problem, with cited survival rates falling to 8% to 12%.

For a patient, resistance means that a medicine which previously controlled the cancer may stop working well enough. The Taiwanese project seeks to address the changes inside cancer cells that allow them to withstand paclitaxel.

Taiwan's patients include many younger women

Studies in Taiwan place TNBC at about 10% to 15% of all breast cancer cases, compared with the worldwide estimate of 10% to 20%. The Taiwanese range falls within the global range, while the local age figures point to a particular concern for younger patients.

The average age at onset in Taiwan is 46, described as substantially younger than the global average. About 20% of Taiwanese TNBC cases occur in women under 40. In simple terms, that is one in five cases.

These figures help explain the urgency behind developing additional treatments locally. Patients may face an aggressive cancer at a relatively young age, and a recurrence can bring the added difficulty of resistance to a medicine that had been central to their treatment.

Which treatments are already available?

Chemotherapy has been the backbone of TNBC treatment for decades. In Taiwan, most patients still receive combination chemotherapy as their first treatment. Access to newer targeted medicines remains limited by costs and regulatory barriers.

Several newer approaches have emerged internationally. They work in different ways and are suitable for different groups of patients, leaving substantial unmet needs, especially when chemotherapy resistance develops.

• PARP inhibitors target mechanisms that repair damaged DNA. They are effective in a small subset of patients with mutations in the BRCA1 or BRCA2 genes.
• Immune checkpoint inhibitors include pembrolizumab, which blocks PD-1. These medicines have shown promise, especially for patients whose tumors express the PD-L1 protein.
• Antibody-drug conjugates deliver chemotherapy directly to cancer cells. They are also used in other breast cancer types and are not specific to TNBC.

DNA repair is a cell's way of fixing damage to its genetic instructions. Immune checkpoint treatment acts on controls affecting the immune response, while an antibody-drug conjugate joins a targeting antibody to a cancer medicine. Each approach offers a different way to attack cancer.

The KIF2C candidate would add another approach: targeting a protein associated with resistance to an existing chemotherapy drug. Its proposed role is closely tied to paclitaxel, rather than replacing all the treatments already used for TNBC.

How blocking KIF2C could help paclitaxel work

KIF2C belongs to the kinesin family of proteins and is involved in cell division. It plays a role in the mitotic spindle apparatus, the machinery a cell uses when dividing. Cancer cells depend on division to keep multiplying.

When KIF2C is overactive in cancer cells, it helps them evade the effects of paclitaxel. Higher levels of KIF2C have also been associated with poorer outcomes and greater drug resistance in several cancer types. The researchers identified it as a key driver of resistance in TNBC cells.

The new candidate is a small molecule designed to enter cells and inhibit KIF2C activity. Blocking that activity disrupts the division process and makes cancer cells more susceptible to chemotherapy. The research describes the approach as restoring paclitaxel's effectiveness and preventing cancer cells from developing resistance in the experimental setting.

Laboratory studies found that the candidate and paclitaxel worked more effectively together than either did alone. The central idea is straightforward: interfere with a mechanism cancer cells use to survive treatment, then allow the chemotherapy to exert a stronger effect.

For TNBC, this provides a potential target inside the cell despite the absence of the hormone and HER2 receptors used by other breast cancer medicines. It represents a proposed new class of targeted treatment for cancers that have relied heavily on chemotherapy.

What the researchers say about the discovery

Professor Lily Hui-ching Wang, a leading member of the research team, described the treatment problem facing patients whose TNBC returns and explained why the group focused on paclitaxel resistance.

Once triple-negative breast cancer recurs, resistance to paclitaxel becomes a major obstacle, and survival rates drop dramatically. Our new drug offers hope for overcoming this resistance and improving outcomes for patients who have few alternatives.

Dr. Hsieh Hsing-pang, director of the NHRI's Institute of Biotechnology and Pharmaceutical Research, described the candidate's claimed global novelty and its potential use alongside paclitaxel.

This is the world's first cell-penetrating small-molecule inhibitor of KIF2C. Its synergy with paclitaxel could set a new standard for treating not only TNBC but also other gynecological cancers.

The team has also applied the candidate to ovarian, endometrial and cervical cancers. That work suggests a broader research opportunity, with the same strategy potentially relevant to several cancers affecting women.

The discovery has attracted international attention and is scheduled to appear as the cover story in the August edition of the journal Developmental Cell. That forthcoming publication places the research alongside the next stages of drug development.

Genetic testing could help guide treatment choices

Precision medicine means choosing treatment with attention to the particular biological features of a patient's cancer. Genomic profiling has shown that TNBC is a collection of subtypes with different genetic and molecular features, rather than a single uniform disease.

Comprehensive genomic profiling (CGP) examines hundreds of genes associated with cancer. It can identify actionable mutations, meaning genetic changes that may help guide a treatment choice, and biomarkers that may predict a response to targeted medicines.

Studies in Taiwan have identified frequent mutations in genes including TP53, PIK3CA and APC among patients with TNBC. Mutations in TP53 and APC are particularly common and have been linked to poorer outcomes. These findings are helping guide the development of treatments tailored to the features of individual cancers.

Two other measures are gaining attention: tumor mutational burden (TMB) and homologous recombination deficiency (HRD). TMB describes the amount of genetic change in a tumor and is emerging as a predictor of response to immunotherapy. HRD concerns a weakness in a DNA repair process and is emerging as a predictor of response to PARP inhibitors.

Bringing CGP into routine care could help identify patients most likely to benefit from new therapies, including the proposed KIF2C inhibitor. Access to genomic profiling and targeted treatment remains limited for many Taiwanese patients, making locally developed options an important part of the effort to expand care.

How another Taiwanese project takes a different approach

Shine-On Biomedical's SOB100 is another example of Taiwan's work on difficult cancers. The platform uses engineered exosomes to deliver drugs and targets HLA-G proteins, which are present at high levels in cancers including glioblastoma and TNBC.

Exosomes serve as tiny delivery packages in this approach. SOB100 is designed to carry medicines directly to cancer cells, cross barriers such as the blood-brain barrier and minimize side effects. The blood-brain barrier is the protective boundary that can make delivery of medicines to the brain difficult.

The KIF2C candidate and SOB100 address different parts of the treatment problem. KIF2C inhibition focuses on activity inside cancer cells linked to chemotherapy resistance. SOB100 focuses on directing drug delivery toward cancer cells and reaching places that are difficult for medicines to enter.

Both projects reflect Taiwan's growing expertise in precision oncology and efforts to develop therapies suited to the genetic and clinical characteristics of Asian patients. Taiwan's work in genomics and drug development is directed toward treatment needs within its own population and across the wider Asian and global setting.

What must happen before patients can receive the drug?

The KIF2C candidate must undergo clinical trials to assess its safety and effectiveness in people. Preclinical work is the testing stage before those trials. Moving from laboratory results to patient treatment requires a further development process.

Regulatory approval in Taiwan and internationally will require work with regulators and industry partners. Access and affordability are also central concerns, particularly for patients with lower incomes or those living in rural areas.

International partnerships, including those seen with SOB100, may help speed development, approval and distribution. For the KIF2C project, the stated hope is to begin clinical trials soon and reach the market within five years if development succeeds. No specific trial start date was given.

The dates and stages described as of July 5, 2025, are:

• July 4, 2025: NHRI and NTHU announced the KIF2C drug candidate and its potential to address paclitaxel resistance.
• July 5, 2025: The candidate remained in preclinical testing, supported by the National Science and Technology Council.
• August 2025: The research was scheduled to feature as the cover story in Developmental Cell.
• Within five years: The team hoped the treatment could reach the market if testing and development succeeded.

For patients, the proposed benefit is a further treatment option when resistance makes chemotherapy less effective. Delivering that benefit will depend on human testing, approval and practical access to the medicine. Taiwan's contribution is a locally developed candidate aimed at a specific and difficult problem in cancer care.

Key Points

• NHRI and NTHU announced a KIF2C inhibitor candidate on July 4, 2025, targeting resistance to paclitaxel in triple-negative breast cancer.
• TNBC accounts for about 10% to 20% of breast cancer cases worldwide and 10% to 15% in Taiwan.
• The average age at onset in Taiwan is 46, and 20% of cases occur in women under 40.
• The researchers describe the candidate as the world's first cell-penetrating small-molecule inhibitor of KIF2C.
• Laboratory testing found the candidate more effective with paclitaxel than either treatment alone. Research also extends to ovarian, endometrial and cervical cancers.
• Genomic profiling and Taiwan's separate SOB100 drug delivery project represent other efforts to tailor cancer treatment.
• The candidate remains in preclinical testing. Clinical trials, regulatory approval and affordable access are necessary steps toward patient use.
• The research is scheduled for the August edition of Developmental Cell, with a conditional hope of reaching the market within five years.