Source: Taipei Times

Researchers from Taipei Medical University (TMU) and the University of California, San Francisco (UCSF) have developed a method that could potentially improve the effects of chemotherapy and immunotherapy in cancer patients.

Tsai Kun-chih (蔡坤志), a professor at TMU’s Graduate Institute of Clinical Medicine, told a news conference in Taipei on Monday that about 70 percent of all solid tumors in patients are drug resistant prior to treatment.

The tumors not only respond poorly to chemotherapy, but are also resistant to immune cells naturally produced by the body or administered as part of treatment, said Tsai, who also heads the Taipei Municipal Wanfang Hospital’s clinical research center.

Traditional chemotherapy can only inhibit about 30 percent of cancer growth, while immunotherapy, which has grown in use in the past few years, is only effective for about 15 percent of patients, he said.

The researchers discovered five years ago that tumor cells in patients have a self-protection mechanism called the “death checkpoint,” which makes them resistant to chemotherapy, radiotherapy and immunotherapy, TMU said.

At the heart of that resistance can be a protein called nuclear receptor corepressor 2 (NCOR2), which inhibits antitumor immunity and natural stress responses.

To overcome the problem, Tsai said the team developed “NCOR2 decoy gene therapy,” which could suppress a tumor cell’s resistance to drugs.

In various animal preclinical studies, the therapy, combined with either chemotherapeutic drugs or immune checkpoint inhibitors, greatly improved the response rate in difficult-to-treat cancers such as triple-negative breast cancer and pancreatic cancer from the initial 30 percent to more than 90 percent.

Speaking over teleconferencing, UCSF researchers said they studied the therapy on difficult-to-treat breast cancers and pancreatic cancer, and have also made progress with brain cancer.

NCOR2 decoy gene therapy could be effective in treating many different cancers, they added.

Tsai said they expect that their solution could enter the animal clinical testing stage within three to five years.

The study by TMU and UCSF researchers, titled “Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity,” was published in the journal Nature Cancer on May 26.