A recent study by WEHI researchers has discovered that a new combination of two cancer drugs has the potential to be a future treatment for patients with acute myeloid leukaemia (AML), which is a common type of blood cancer.
The study found that the combination of two existing drugs was able to eliminate AML cancer cells in laboratory tests. This breakthrough has the potential to lead to clinical trials in the near future.
The testing of a combination of two existing drugs successfully eliminated AML cancer cells in laboratory tests. The findings, which were published in Cancer Cell, are a promising development that could lead to clinical trials in the near future. This offers hope for the 1100 Australians who are diagnosed with AML each year.
Key Points:
- Researchers at WEHI conducted the first-ever test of a dual drug combination against AML, which effectively killed cancer cells in laboratory tests.
- The treatment involved a combination of venetoclax, a current standard-of-care drug for AML, and a STING agonist, which is a new type of immunotherapy drug.The combination of drugs was effective in treating the more aggressive and difficult to manage types of AML. This breakthrough could also impact the use of STING agonist drugs in treating other forms of cancer. The research team from WEHI paired venetoclax, a commonly used anti-cancer drug for AML, with a STING agonist, which is a new type of immunotherapy drug. Venetoclax was developed based on a significant research finding at WEHI. The team, led by Dr. Sarah Diepstraten, studied various blood cancers, including samples from patients with AML.ML and treated them in the lab with the drug combination, leading to impressive results. “It’s really impressive — combining venetoclax with this emerging immunotherapy treatment can actually eradicate AML,” said Dr Diepstraten. “This is the one-two punch combo that could be the knockout blow for AML. You could almost paraphrase the famous boxer Muhammed Ali and say this treatment floats like a butterfly, and STINGs like a bee.” Critically, the combination treatment showed high promise in AML samples that were driven by a mutated p53 protein, a type of AML that is generally more aggressive.Cancer becomes more difficult to treat when the p53 protein is mutated and becomes defective in groups of cells. This mutation significantly increases a person’s risk of developing cancer.
The p53 protein is crucial in preventing the formation of cancerous cells by causing the death or halting the growth of damaged or abnormal cells when it is working effectively.
Mutations of p53 are believed to be the main driver of cancer development and are present in half of all human cancers worldwide.
As cancers associated with p53 mutations tend to be more aggressive and harder to treat.
There is a critical need for better therapies to treat AML (acute myeloid leukemia), which is often aggressive and resistant to treatment.
Dr. Diepstraten stated, “For AML patients with mutated protein that causes less therapy-induced death of their leukemia cells, combining venetoclax with a STING agonist results in more killing of AML cells compared to treating with venetoclax alone.”
The treatment was highly effective at killing cancer cells in both samples with and without the p53 mutation. This is exciting news considering the lack of effective treatments for aggressive cancers driven by mutations in p53.
The goal is to see more and more patients achieving long-term remission from AML.
Blood cancers such as AML could potentially benefit from the addition of STING agonists to the treatment plan, as researchers believe it could be a crucial component.”
Uncovering the Role of STING in Cancer
This study is the first to utilize a STING agonist to directly target mechanisms within cancer cells, encouraging the natural processes that lead to their demise.
Up to now, STING agonist immunotherapy drugs have primarily been utilized to combat solid tumors by stimulating the body’s immune response.
This new research enhances our understanding of how STING agonists function and suggests for the first time that they could be effective in ways beyond what was previously known.had not been previously anticipated: against blood cancers, and by directly targeting the cancer cells intrinsically.
Associate Professor Gemma Kelly, co-senior author on the study, explained that both venetoclax and the STING agonists worked together to kill cancer cells at the cellular level.
“Venetoclax disrupts the cell’s machinery that keeps it alive. In some blood cancers where this response is not optimal, STING agonists can enhance this effect to deal a deadly blow to cancer,” Assoc Prof Kelly, a laboratory head in WEHI’s Blood Cells and Blood Cancer division, said.
“ItThe combination of these two medications resulted in the highly effective elimination of AML cancer cells in our laboratory tests, producing results that were truly remarkable.” said WEHI lab head Professor Andrew Wei, co-senior author of the study. Further research is necessary, but the findings are very promising. “Early clinical trials in solid cancers have shown that STING agonists are well tolerated in the body,” said Prof Wei, “These results provide new hope for patients with the most resistant forms of leukemia. Since STING agonists are currently being tested in clinical trials, we hope to conduct human studies using STING in the near future.”
Our research has discovered a potential new treatment approach for patients with highly resistant and deadly forms of acute leukemia. This is a significant breakthrough and has the potential to significantly impact clinical outcomes.
WEHI researchers and clinicians are now working with Aculeus Therapeutics to translate these findings into a new clinical trial for AML patients. Aculeus Therapeutics, a local biotechnology company, has developed a powerful STING agonist and we are excited to see the potential impact of this research in the near future.
Dr. Mark Devlin, CEO of Aculeus Therapeutics, expressed his excitement about the potential of this new treatment approach and the opportunity to collaborate with WEHI researchers and clinicians.The potential of the recent discovery by WEHI has been discussed. According to Aculeus, drug discovery and development are collaborative efforts, with a promising new drug, ACU-0943, being developed. The collaboration with WEHI teams, who have a deep understanding of disease biology and the clinical landscape, will help shape how the drug will be used most effectively. Aculeus’ STING agonist, ACU-0943, is expected to enter clinical development for the treatment of AML later this year.
