MARCH5 is a master regulator of BCL2 proteins and a potential anti-cancer drug target

Dr Mark F van Delft

The Walter and Eliza Hall Institute of Medical Research (VIC)

$449,996

2024 - 2027

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The Research

This year, around 6000 Australians are expected to die from blood cancer. Blood cancers are indiscriminate and impact people of all ages, genders and ethnic backgrounds. These cancers often evade the normal process of cell death – a characteristic that makes them difficult to treat with standard therapies. To counter this problem, Australian scientists developed a targeted drug called venetoclax that inhibits a critical survival protein and re-awakens cell death in many blood cancer cells. Venetoclax is now used to treat blood cancers worldwide, replacing chemotherapy in the treatment of chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML), respectively the most common and one of the most severe blood cancers. 

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Whilst venetoclax is a well-tolerated and effective treatment for some blood cancers, it has two major limitations. The first is that many blood cancers and the majority of solid cancers do not respond to this drug. The second is that for patients that do respond, in most cases the duration of benefit is time-limited – venetoclax therapy fails to cure the disease because enduring cancer cells resist treatment and cause the disease to return.

This project aims to enhance the action of venetoclax, rendering resistant cancer cells sensitive to treatment. This will broaden the spectrum of patients who can benefit and lead to deeper, longer lasting and more durable treatment responses.  

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