Leading the way in blood cancer research

Leading the way in blood cancer research

Illuminate newsletter header, Spring 2021
September 2021

Dr Gemma Kelly
Blood cancer researcher Dr Gemma Kelly.

A long-term commitment to discovery and a vision to improve survival for people with blood cancers has kept WEHI at the forefront of blood cancer research and treatments. 

For more than 60 years, WEHI has been studying blood and immune cells. Together with our collaborators and partners, we have made transformative discoveries that have underpinned new medicines that have changed and saved lives. 

Blood cancers include leukaemias, lymphomas and myeloma, and account for one in 10 cancers diagnosed in Australia each year.

Our researchers are continuing their work to better understand what causes blood cancers, find better cancer treatments and improve existing therapies, including tackling drug resistance. 

Cancer-fighting secret weapon 

Half of all cancers in the world, including many blood cancers, are linked to mutations in the tumour suppressor gene p53

Some people will not respond or will become resistant to new drugs. WEHI researchers are unravelling the molecular answers for why this happens, paving the way for new therapies. 

WEHI researchers were able to solve a long-standing mystery about how p53 acts to suppress cancer development in blood cells, discovering the link between p53 and a group of ‘DNA repair’ genes that were vital to its effectiveness in preventing lymphoma and leukaemia, as well as other cancers.

Combining expertise in cancer biology and bioinformatics, our researchers also demonstrated that mutated p53 proteins could stop healthy p53 proteins from activating pathways in the cells that protect against cancer. However, the healthy p53 proteins were still able to activate pathways that promoted tumour growth.

Blood cancer researcher Dr Gemma Kelly said it showed that mutant proteins were ‘cunning’.

“p53’s role in cancer is clearly more complicated than we had expected,” she said.

Achilles’ heel of blood cancers 

Anti-cancer agents called BH3- mimetics target pro-survival proteins. The success of BH3-mimetic drugs in treating blood cancers has led to considerable interest in discovering treatments that target other pro-survival proteins. 

MCL-1, a member of the same family of proteins as BCL-2, is critical for the survival of certain blood cancers, including lymphoma and myeloma. WEHI established a research collaboration with international pharmaceutical company Servier to facilitate the development of new agents targeting MCL-1, called MCL-1 inhibitors. 

Associate Professor Marco Herold said MCL-1 inhibitors could be particularly powerful when combined with standard treatments such as chemotherapy.

“In our preclinical model, we found that combining an MCL-1 inhibitor with chemotherapy led to remission in almost all cases of lymphoma.

"Our laboratory model will be invaluable for future preclinical work to determine the best uses of MCL-1 inhibitors for treating human disease,” he said.

Improving treatments 

Cancers are made up of millions of individual cells, and differences in these cells can affect how well it responds to treatment.

A research team from WEHI and Stanford University used a revolutionary technique called CyTOF and machine learning to distinguish which cells survived treatment with standard medicines used to treat myeloma – and see how they differed from cells that were sensitive to these medicines.

The technique could be integrated into clinical trials both to understand why some patients are resistant to anti-cancer therapies, and to match patients with the most effective therapies for their disease. 

While new treatments give many people increased hope in their treatment options, inevitably some people will not respond or become resistant to new drugs. WEHI researchers are unravelling the molecular answers for why this happens, paving the way for new therapies. 

This research represents the work of more than 100 researchers across WEHI and many years of study. 

WEHI discoveries 

  • Colony stimulating factors (CSFs) boost production of infection-fighting white blood cells. In 1991, they were approved for use as a supportive therapy in cancer patients, the culmination of 25 years’ work at WEHI discovering and purifying CSFs. The treatment has helped more than 30 million people worldwide. 
  • In 2016, anti-cancer treatment venetoclax was approved in the US, Europe and Australia for people with certain forms of chronic lymphocytic leukaemia. Venetoclax was developed by AbbVie and Genentech (a member of the Roche group) and was discovered as part of a research collaboration involving WEHI. Its use has been expanded to other blood cancers.

 

 

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