Research team gains edge in fighting cancer

Local | Riley Chan 31 Oct 2017

A research team at the University of Hong Kong has found a new approach to mitigating cancer growth and boosting the effectiveness of immunotherapy on liver cancer.

Liver cancer is the third most deadly form of the disease in Hong Kong. It has a high recurrence rate, with 80 percent of cases inoperable.

Immunotherapy boosts natural defenses to fight cancer cells and has few side effects, but it has worked on only about 20 percent of liver cancer patients.

That could might change following a two-year study led by the Li Ka Shing Faculty of Medicine's department of pathology, with researchers looking into the mechanism of liver cancer.

They found white blood cells that attack cancer cells are deactivated when an enzyme is over-expressed in liver cancer tissues, which explains the ineffectiveness of immunotherapy on some patients.

According to assistant professor Carmen Wong Chak-lui, who led the research, 60-70 percent of patients show a high expression of enzyme ENTPD2.

A T cell is a subtype of white blood cell that plays a central role in killing cancer cells, but when ENTPD2 is over- expressed it produces the compound adenosine monophosphate.

And the research shows AMP attracts many immunosuppressive myeloid cells, which allow cancers to escape immune surveillance and become non-responsive to blockade. These cells deactivate and reduce the number of T cells.

Using mice, it was found that an ENTPD2 inhibitor with an immune checkpoint inhibitor can reduce tumor size threefold in two weeks, while immunotherapy alone only showed half that effectiveness.

A separate model led to three mice dying during a 90-day treatment of immunotherapy. But those receiving both ENTPD2 inhibitor and immune checkpoint inhibitor had a 100 percent survival rate.

"A lot of past studies only focused on the cancer cells," said David Chiu Kung-chung, a PhD candidate who took part in the research. "They found a certain drug that can kill all cancer cells, but when they apply it on the body the drug became ineffective. It is because our opponents have never been only cancer cells."

According to him, ENTPD2 is not a crucial enzyme in the body. So even a high dosage of ENTPD2 inhibitor will not pose significant side effects to a patient.

Department head Irene Ng Oi-lin said it is too early to say when a drug may be available. But there is confidence the findings will help liver cancer patients and perhaps others react to immunotherapy.

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