When cells forget how to die – a hallmark of cancer

22 November, 2019

Andreas Strasser and David Vaux win $50,000 CSL Florey Medal for Lifetime Achievement for identifying cell death triggers and using them to fight cancer.

Past CSL Florey Medallists include Graeme Clark, Ian Frazer, and Nobel Laureates Barry Marshall and Robin Warren.

Professor Andreas Strasser with Professor David Vaux. Image credit: Walter and Eliza Hall Institute

In the late 1980s to early 1990s, two Melbourne scientists, Andreas Strasser and David Vaux, discovered the molecular processes that cause billions of cells in each of us to die every day. They showed that some cancer’s cells can evade this process of programmed cell death and ‘fail to die’. So far, their findings have led to powerful new treatments for leukaemia and opened a new field of research which generates 25,000 papers every year. And, they say, there is still much to learn.

Professors Strasser and Vaux, both of Melbourne’s Walter and Eliza Hall Institute of Medical Research, have been awarded the biennial CSL Florey Medal, presented by the Australian Institute of Policy and Science (AIPS) at the Association of Australian Medical Research Institutes annual dinner at Parliament House.

The two scientists provided the first insights into the molecular mechanisms for cell death, and the first evidence that the failure of cells to undergo programmed death can lead to cancer and autoimmune disease.

The research showed that not all cancer-causing genes trigger runaway cell growth; some act by stopping the body’s normal process used to remove unwanted cells, a process known as apoptosis. Due to Vaux and Strasser’s work, avoidance of cell death is now recognised as one of the universally accepted “Hallmarks of Cancer”.

David Vaux is Deputy Director, Science Integrity and Ethics of the Walter and Eliza Hall Institute, and Andreas Strasser is the head of its Blood Cells and Blood Cancer division. Their research together began with the discovery of the function of a gene called Bcl-2. They found it can keep cancer cells alive, and increase their resistance to chemotherapy. After discovering that Bcl-2’s primary function was to inhibit apoptosis, they and their teams worked on its regulation and roles in normal health and disease. Their discoveries underpinned development of a potent new inhibitor of Bcl-2 by others at the Walter and Eliza Hall Institute, in collaboration with US pharmaceutical companies Genentech (a member of the Roche Group) and AbbVie, that is now being used to treat leukaemia around the world.

David Vaux says he is honoured to be the joint recipient of the award, which is named after Australian Nobel laureate, the late Sir Howard Florey, who – together with Ernst Chain – brought penicillin to the clinic.

“I’m proud to share this honour with Andreas,” he says. “Bcl-2 was the spark that ignited a whole new field that has given new insights not only into the origins of cancer, but also, as first shown by Andreas, autoimmune disease. But cell death research has only just begun.”

Andreas Strasser agrees. “Although our research into cell death and cancer has been underway for decades, it remains for me a vital and exciting field,” he says. “There still remains much to be discovered and there is a real opportunity to translate the understanding or programmed cell death into improved therapies for diverse cancers.”

CSL’s Chief Scientific Officer, Professor Andrew Cuthbertson, adds that the research has global ramifications.

“Andreas and David’s discoveries are the basis for thousands of journal papers every year and have had a significant impact on the field of oncology research,” he says. “Their work further enhances Australia’s reputation for producing world-class research. We congratulate them on their achievements.”

AIPS director Peter McMahon accords the research in the highest degree of importance in the field.

“The ‘Hallmarks of Cancer’ constitute a global research framework,” he says. “Andreas Strasser and David Vaux have played a major role in building it.”

Images

Image credit: Walter and Eliza Hall Institute

Images from the award ceremony

David Vaux and Bernie Hobbs. Photo: Bradley Cummings

Image credit: AAMRI/Bradley Cummings

Videos

High resolution videos available upon request

Credit: Walter and Eliza Hall Institute

More information

Die hard: Targeting cell death in disease treatments

Professors David Vaux and Andreas Strasser

Scientists revealing the links between cell death and cancer win $50,000 CSL Florey Medal for lifetime achievement

More than 30 billion cells die in every human every day. They do this through a process known as apoptosis, or programmed cell death – the body’s primary method of ensuring that old and damaged cells do not outstay their welcome and cause disease.

Cancer has long been known to be driven by defects in genes that trigger unrestrained cell growth. But, during the past three decades, molecular biologists Andreas Strasser and David Vaux from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, established that there was another way damaged genes could cause cancer.

The researchers showed that a protein called Bcl-2 regulates cell death. Bcl-2 was the first component of the cell death mechanism to be recognised, and has allowed other parts of this complex mechanism to be identified piece by piece. As over a million cells in our bodies undergo apoptosis every second, it is vitally important that it doesn’t go wrong.

Due to genetic mutations, some leukemia and lymphoma cells produce too much Bcl-2. It was initially assumed this cause the malignant cells to proliferate, but Strasser and Vaux show that rather than stimulating cell division, Bcl-2 stopped cancer cells from being able to die by apoptosis.

The discovery by Vaux and Strasser that the evasion of normal programmed cell death played a key role in cancer development was startling and spurred a whole new field of study.

The clear implication of their findings was that drugs designed to kickstart the cell death process could be used to treat diseases, in particular cancer.

The work of Strasser and Vaux was the foundation for development of the drug Venetoclax by researchers at the Walter and Eliza Hall Institute, in association with the pharmaceutical companies Genentech (a member of the Roche Group) and AbbVie. It is already in widespread use, combatting chronic lymphocytic leukaemia, the most common form of leukaemia diagnosed in Australia. Related drugs are in clinical trials for several other cancers.

The role cell death plays in the development of disease is now considered so fundamental that, since 2011, it has been included as one of the universally accepted “Hallmarks of Cancer”.

Professor David Vaux is Deputy Director, Science Integrity and Ethics of the Walter and Eliza Hall Institute. After graduating in medicine, he undertook his PhD at the Institute, studying the Bcl-2 gene. After three years at Stanford University in the US he returned to Australia in 1993. His work has not only resulted in new treatments for serious disease, but also catalysed widespread interest in the molecular biology of cell death, prompting researchers around the world to develop novel treatments for many conditions.

Professor Andreas Strasser holds the Alan W. Harris Personal Chair in Experimental Cancer Biology at the Walter and Eliza Hall Institute and is head of its Blood Cells and Blood Cancer division. He attained his PhD at the Basel Institute for Immunology and University of Basel, in Switzerland, and moved to Melbourne in 1989.

Throughout his career, his research has focussed on the role of cell death, especially in cancer and the immune system.

The CSL Florey Medal

The Florey Medal is awarded biennially to an Australian biomedical researcher for significant achievements in biomedical science and/or human health advancement. In addition to the silver medal, the award currently carries a prize of $50,000 due to the generous support of CSL Limited.

This award was established in 1998 by the Australian Institute of Policy and Science in honour of the Australian Nobel Prize-winning scientist, Sir Howard Florey, who developed penicillin.

The Florey Medal is part of the Tall Poppy Campaign which aims to recognise and promote scientific and intellectual excellence in Australia.

Past winners are:

2017 – Professor Elizabeth Rakoczy

Development of a new gene therapy for wet age-related macular degeneration (AMD).

2015 – Professor Perry Bartlett

Discovery of brain stem cells, transforming our understanding of the brain development and function.

2013 – Professor Ruth Bishop

Discovery of rotavirus and the fight against this virus that has killed millions of young children through acute gastroenteritis.

2011 – Professor Graeme Clark

Development of Australia’s bionic ear.

2009 – Professor John Hopwood

Diagnosis and treatment of genetically inherited disorders that affect children with clinical effects leading to progressive destruction of the brain and other organs.

2006 – Professor Ian Frazer

Research towards the development of vaccines against human papillomaviruses, including cervical cancer and genital warts affecting the lives of millions globally.

2004 – Professor Peter Colman

Structural biology research, particularly for the discovery of a new class of anti-influenza drug.

2002 – Professor Colin Masters

Work relating to Alzheimer’s disease.

2000 – Professor Jacques Miller

Discovery of the function of the thymus which signalled a seminal contribution to immunology.

1998 – Dr Robin Warren and Professor Barry Marshall

Discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.

The Medal

The Florey Medal is hand sculpted by Michael Meszaros. Michael has lived as a sculptor in Melbourne for nearly four decades, producing a wide range of work ranging from major public pieces to his speciality of medals. He learned this from his father Andor, also a sculptor and medallist of international reputation.

This work is closely based on a portrait medal Andor made when Sir Howard Florey sat for him in 1963, commissioned by the Florey Institute at The University of Melbourne. Michael met Sir Howard at the time. Using Andor’s original as a guide, Michael has remodelled it in this size, adding a different inscription, designing a reverse and casting it in bright sterling silver.

The Australian Institute of Policy and Science (AIPS)

The Australian Institute of Policy and Science is an independent and non-partisan not-for-profit organisation first founded in 1932. They have grown with Australia’s public policy history and work to:

increase public engagement in science
promote excellence in research, innovation and the promotion and communication of science
inform and influence policy and policy-making
invest in a scientifically inspired, literate and skilled Australia that contributes to local and global social challenges.

AIPS achieves its objectives through an extensive network of partners spanning university, government, industry and community actors.