Towards a cure for cancer

The development of anti-cancer drug venetoclax and clinical trials were preceded by two decades of research into how BCL-2 controls cell survival. 

Walter and Eliza Hall Institute scientists contributed to many of the important discoveries underpinning venetoclax's development.

"It was generally thought that cancer genes were just normal genes that regulated cell growth. 

But when they were mutated, they caused cells to proliferate in an uncontrolled way." 
– David Vaux


Bcl-2 makes cancer cells immortal

David Vaux, working with Suzanne Cory and Jerry Adams, discovers that the protein BCL-2 makes leukaemia cells live indefinitely

This is the first time prolonged cell survival has been implicated in cancer development and progression.

A cancer revolution

It used to be thought that cancer was simply due to too many cells being created. David Vaux discovers that some cancers are due to the opposite process: not the birth of too many cells, but to genetic errors that prevent unwanted cells from dying when they should.


Elevated BCL-2 thwarts anti-cancer treatments

Andreas Strasser, with Suzanne Cory and Alan Harris, discovers cells with abnormally high levels of BCL-2 are resistant to anti-cancer drugs and radiation treatment. 

"These studies suggested for the first time that anti-cancer drugs could kill tumour cells by inducing programmed cell death" – Andreas Strasser


Trigger protein for cell death identified

A team of Walter and Eliza Hall Institute scientists including David Huang, Liam O'Connor and others identify a protein, called BIM, that triggers cell death.

BCL-2 keeps cells alive by binding to and suppressing BIM and related proteins. BH3-mimetic drugs including venetoclax are later designed to mimic death proteins such as BIM, suppressing BCL-2's ability to keep cells alive.

1999, 2003

BH3-only proteins critical for drug-induced death of cancer cells

Philippe Bouillet, Andreas Strasser, Jerry Adams and others show that the activation of BH3-only proteins such as BIM is critical if tumour cells are to be killed by anti-cancer drugs.

"If you have too much Bcl-2 in the wrong cell at the wrong time, it can lead to the development of lymphoma or leukaemia – not on its own, but in partnership with other things that go wrong in the genes. 
So, we thought, maybe you can attack cancer by taking Bcl-2 away, or developing a drug that would reduce the activity of Bcl-2 in the cell." – David Huang


BH3-only proteins selectively target survival proteins in cancer cells

Research from David Huang and colleagues shows BH3-only proteins interact selectively with members of the BCL-2 protein family. 

Subsequently Doug Fairlie designed a new BH3-only protein that could target a single member of this family. These findings provided a road map for the design and discovery of BH3-mimetic drugs.


Compounds found that block the function of Bcl-2 family proteins

Institute scientists including David Huang, Keith Watson, Ian Street, Jonathan Baell, Guillaume Lessene, Peter Czabotar and Peter Colman, discover benzothiazole compounds block the function of a BCL-2 family protein.

Patents describing these compounds are licensed to pharmaceutical company Genentech. A year later Genentech introduces pharmaceutical company Abbott (later named AbbVie) into what becomes a three-way collaboration.


Venetoclax developed and tested

Laboratory testing of a BH3-mimetic drug, venetoclax, reveals its promise in treating cancers with high levels of BCL-2. 

Venetoclax was co-developed for clinical use by AbbVie and Genentech, a member of the Roche group, and was discovered by AbbVie scientists as part of the joint research collaboration with Walter and Eliza Hall Institute scientists. 

The Huang and Roberts laboratory teams were the first to test the drug on leukaemia cells obtained from patients.


First clinical trials of venetoclax

People with chronic lymphocytic leukaemia (CLL) in Melbourne are the first in the world to be treated with venetoclax in phase I clinical trials

Even from an early stage there are hopeful signs that the drug lowers leukaemia cell numbers in patients for whom there are no conventional treatment options available.


phase I trial: preliminary results announced

Phase I clinical trials of venetoclax show highly promising results for treating advanced CLL. 

Final trial results released in December 2015 confirm the potency of venetoclax. Twenty per cent of patients treated with venetoclax in these trials achieve complete clearance of the cancer, and 54 per cent show partial clearance.


phase II clinical trials: impressive RESULTS FOR VENETOCLAX

Clinical trials conducted internationally, including in Australia, demonstrate venetoclax is effective for treating advanced forms of CLL

Seventy nine per cent of people involved in the phase II trial had a promising response to the treatment.

Substantial reductions

Andrew Roberts said most trial patients responded positively to the therapy, showing substantial reductions in the number of leukaemia cells in their body. Updated results of the phase I study also confirmed that these responses could be lasting.

"Many patients have maintained this response more than a year after their treatment began, and some patients remain in remission more than four years on." 
– Andrew Roberts
Venetoclax clinical trial participants Victor (left) and Rodney.  Credit: Royal Melbourne Hospital

2016, 2017


The US, EU and Australian drug regulatory bodies approves venetoclax for treating certain forms of chronic lymphocytic leukaemia. This enables doctors to prescribe venetoclax to patients with these forms of blood cancer. 

Venetoclax is now undergoing clinical trials in other blood cancers with the hope that it could have benefits for more patients to come.

A few of the faces behind the development of venetoclax, photographed at the Walter and Eliza Hall Institute, May 2016 (L-R): Professor Andrew Roberts, Dr Ian Street, Professor Jerry Adams, Associate Professor Guillaume Lessene, Professor Suzanne Cory, Dr Keith Watson, Professor David Vaux, Dr Julian Clark, Professor David Huang and Professor Peter Colman

We acknowledge this work is the result of many years of collaboration between teams of teams. More than 100 institute staff and students have been involved in the development of venetoclax – too many to list here. Thank you to all who have contributed to this enormous body of work.

More information

Cancer research at the Walter and Eliza Hall Institute

100 years of discoveries for humanity

About the Walter and Eliza Hall Institute