Combination treatment for blood cancer: Study shows two drugs kill cancer cells

A new combination of two cancer drugs has shown great promise as a future treatment for patients with acute myeloid leukaemia (AML), one of the most common types of blood cancer. A new study by scientists at WEHI (Walter and Eliza Hall Institute of Medical Research) has found that a combination of two existing drugs kills AML cells in lab tests.

The discovery, published in the journal Cancer Cell, could soon lead to clinical trials, offering hope to the 1,100 Australians diagnosed with AML each year.

Stimulating the “Cell Death Artist” A team of researchers at WEHI combined venetoclax, one of the standard drugs for the treatment of acute myeloid leukemia, with a STING agonist, a new class of immunotherapy drugs. Venetoclax was based on a landmark research discovery at WEHI.

Dr. Sarah Diepstraten, one of the study's co-authors, said the team looked at different types of blood cancers, including cancer samples from patients with AML, and treated them in the laboratory with a combination of drugs, leading to impressive results.

“It's really exciting that combining venetoclax with this new immunotherapy treatment can actually eradicate AML,” Dr. Diepstraten said.

Critical role of p53 protein

The combination treatment has shown promise in AML samples associated with mutated p53 protein, a type of AML that is typically more aggressive and harder to treat. The p53 protein plays a critical role in our body, preventing the formation of cancer cells by protecting and arresting the growth of damaged or abnormal cells. However, p53 mutations significantly increase the risk of developing cancer.

“For AML patients who do not have enough death of their leukemia cells due to this mutation, the combination of venetoclax with a STING agonist causes more AML cell killing than treatment with venetoclax alone,” explains Dr. Diepstraten.

Graphic drawing. Source: Cancer Cell (2024). DOI: 10.1016/j.ccell.2024.04.004

STING agonist in a new role

This study is the first to use a STING agonist to directly target the mechanisms inside cancer cells, stimulating the natural processes that cause them to die. STING agonists have previously been used to attack solid tumors by activating the body's immune response.

Potential clinical trials

Professor Andrew Wei, one of the senior authors of the study, said the results were very promising, although further research was required.

“Early clinical trials in solid tumors have shown that STING agonists are well tolerated, and these results provide new hope for patients with the most resistant forms of leukemia,” said Professor Wei.

WEHI and their clinical partners are now translating these promising results into a new clinical trial for AML patients in collaboration with Melbourne biotech company Aculeus Therapeutics, which is developing its own STING agonist.

Aculeus Therapeutics CEO Dr. Mark Devlin said he is very excited about the potential of WEHI's recent discovery. “Drug development is a team game in science. Aculeus has developed a promising new drug, but collaborating with WEHI teams who deeply understand the disease biology and clinical landscape will help determine how this drug will be used most effectively."

Aculeus' STING agonist, ACU-0943, is expected to enter clinical trials for the treatment of AML later this year.