By Hae-ri Lim
HealthKoreaNews

SEOUL, South Korea, Aug. 4, 2026 — Korean researchers have identified a new strategy for treating drug-resistant breast cancer by targeting fat cells surrounding tumors rather than attacking cancer cells alone.

A joint team led by Professor Sun-Young Kong of the Targeted Therapy Branch at the National Cancer Center and Professor Byung-Heon Kang of the Department of Biological Sciences at Ulsan National Institute of Science and Technology, or UNIST, found that the mitochondrial protein TRAP1 plays a central role in turning normal fat cells into cancer-associated adipocytes.

These altered fat cells help tumors grow by supplying nutrients and growth signals, promoting metastasis and reducing the effectiveness of anticancer drugs.

The researchers found that suppressing TRAP1 disrupted the energy metabolism needed for cancer-associated adipocytes to maintain their tumor-promoting activity.

When TRAP1 was removed from fat cells in mice, mitochondrial activity declined and the conversion of normal adipocytes into cancer-supporting cells was inhibited. Tumor growth fell by as much as 56%, while the effectiveness of existing breast cancer treatments increased when they were administered in combination.

The findings suggest that targeting the tumor microenvironment alongside cancer cells could provide a new way to address treatment resistance.

Oral TRAP1 inhibitor shows potential

The team also tested two TRAP1 inhibitors, gamitrinib and SB-U015, in combination with conventional anticancer drugs. Both combinations produced stronger antitumor effects than the existing treatments alone.

SB-U015, an orally administered candidate now under development, enhanced tumor suppression without showing clear toxicity in the preclinical experiments, according to the researchers.

The study findings have been transferred to SmartinBio, a faculty startup founded at UNIST, where follow-up development of a TRAP1-targeted anticancer therapy is underway.

"This study newly demonstrates that adipocytes in the breast cancer microenvironment play an important role in drug resistance," Kong said. "We confirmed the potential for this approach to develop into a treatment strategy for patients who do not respond sufficiently to existing anticancer drugs."

She added that the team plans to conduct further studies to assess whether TRAP1-targeted therapies can eventually be applied in clinical settings.

Kang said the findings show that anticancer effects can be achieved by regulating mitochondria in otherwise normal fat cells surrounding a tumor.

"This strategy could be used to develop next-generation therapies that target both cancer cells and the tumor microenvironment," he said.

The researchers said the approach may also have potential in other cancers that arise near fatty tissue, including ovarian, pancreatic and prostate cancers. Further studies are planned to evaluate the therapeutic potential and safety of TRAP1 inhibitors.

The study, titled "The pro-tumorigenic functions of cancer-associated adipocytes are dependent on the mitochondrial chaperone tumor necrosis factor receptor-associated protein 1, TRAP1," was published in Signal Transduction and Targeted Therapy.

Nam-goo Yoon and So-yeon Kim of UNIST were co-first authors. Kong and Kang served as co-corresponding authors.

The research was supported by South Korea's Ministry of Science and ICT, the National Research Foundation of Korea, the Korea Drug Development Fund and the National Cancer Center.