How Was Venetoclax Developed? The Australian Story Behind a Breakthrough Cancer Therapy
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How Was Venetoclax Developed? The Australian Story Behind a Breakthrough Cancer Therapy
⏱ In 30 Seconds
- ✓ Venetoclax is a targeted cancer medicine that blocks BCL-2, a protein that helps some cancer cells survive.
- ✓ Its development grew from decades of fundamental research into programmed cell death, or apoptosis.
- ✓ Scientists at WEHI played a key role in transforming BCL-2 from a biological discovery into a therapeutic target.
- ✓ Venetoclax is now used to treat several blood cancers, including chronic lymphocytic leukaemia and acute myeloid leukaemia.
A Personal Note
During my years at WEHI, I had the chance to see the later stages of the Venetoclax story unfolding around me, as clinical trials progressed and decades of research moved towards a treatment that could actually reach patients.
I knew at the time that it was an important scientific achievement. But recently, I happened to read blogs where people with blood cancer and their families were sharing their experiences, and it made me think about Venetoclax from a different perspective.
In a research institute, words such as BCL-2, apoptosis and clinical trials become part of everyday scientific language. Outside the laboratory, however, the same drug can mean something very different. For a patient, it may represent another treatment option and another reason to hope. And that hope extends beyond the patient to the family, relatives and friends waiting alongside them.
That made me want to look back at the story from the beginning: how did research on BCL-2 in a Melbourne laboratory eventually become Venetoclax, a medicine now prescribed to patients around the world?
The answer takes us back several decades, to a fundamental question about cancer biology.
Why do some cancer cells refuse to die?
Today, Venetoclax is recognised as an important targeted therapy for blood cancers, including chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML).
Unlike traditional chemotherapy, Venetoclax targets a specific survival mechanism used by cancer cells.
It blocks a protein called BCL-2, allowing cancer cells to restart a natural process called apoptosis, or programmed cell death. A separate article explains how Venetoclax inhibits BCL-2 in CLL and AML treatment.
But the story of Venetoclax did not begin with a drug.
It began with scientists trying to understand how cells live and die.
The Melbourne Discovery That Changed Cancer Biology
The story begins at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia.
During the 1980s, researchers were investigating a fundamental question:
Why can some cancer cells survive when normal cells are programmed to die?
Much of cancer research focused on how cancer cells grew uncontrollably. But another possibility was emerging.
Cancer could result not only from cells growing too much, but also from cells that should die continuing to survive.
That idea helped change the way scientists thought about cancer.
Cancer was not simply a disease of excessive growth. It could also be a disease in which cells escape death.
Discovering BCL-2: The Survival Mechanism of Cancer Cells
Healthy tissues depend on a balance between cell survival and programmed cell death.
Apoptosis acts as a natural system for removing damaged or unnecessary cells.
Research into BCL-2 revealed something remarkable: rather than simply making cancer cells divide faster, BCL-2 could keep cells alive by preventing apoptosis.
This helped establish a fundamentally different way of thinking about cancer.
A cancer cell did not necessarily need to grow faster if it could simply avoid dying.
And that immediately suggested another possibility:
If some cancer cells depend on BCL-2 to stay alive, could blocking BCL-2 become a treatment?
The Australian Scientists Behind the Discovery
Understanding BCL-2 and its role in cancer involved the work of several scientists at WEHI.
Jerry Adams and Suzanne Cory, together with their colleagues, helped establish the relationship between BCL-2, chromosomal changes and cancer.
David Vaux then demonstrated that BCL-2 could prevent programmed cell death, helping establish the idea that cancer cells can survive by blocking their own death signals.
Together, these discoveries provided the biological foundation for a completely new therapeutic strategy.
Instead of only trying to stop cancer cells from growing, scientists could try to remove the mechanisms keeping them alive.
From BCL-2 Discovery to Venetoclax
Discovering the biology of BCL-2 was one thing. Turning that knowledge into a medicine was another.
It required many more years of research into the molecular machinery controlling apoptosis.
That work eventually led to the development of BH3 mimetics, compounds designed to imitate natural death signals inside the cell and neutralise proteins that keep cancer cells alive.
Early compounds showed that the idea could work, but they also revealed an important problem: blocking related survival proteins could cause unwanted effects in normal cells.
Researchers therefore needed a drug that could target BCL-2 much more selectively.
That effort ultimately produced Venetoclax, a highly selective BCL-2 inhibitor.
Its development turned an idea that had begun with fundamental cell biology into a drug capable of selectively exploiting a vulnerability in certain blood cancers.
Its “-clax” ending also reflects the broader system used in modern medicine naming, explained in why drug names end in “-mab”, “-nib”, and “-clax”.
A Global Collaboration Behind a Breakthrough Drug
The journey from a laboratory discovery in Melbourne to an approved cancer therapy was not the achievement of a single laboratory or institution.
The fundamental discoveries made at WEHI provided part of the biological foundation, while academic researchers, biotechnology companies, pharmaceutical scientists and clinicians helped carry that knowledge through drug development and clinical trials.
It was a long chain of discovery, experimentation, setbacks, refinement and collaboration.
That is what makes the Venetoclax story such a strong example of translational research: knowledge about how a cell survives eventually became a medicine used to treat people with life-threatening cancers.
How Venetoclax Changed Cancer Treatment
Venetoclax helped establish a new way of treating cancers that depend heavily on BCL-2.
Rather than broadly damaging rapidly dividing cells, it targets a specific molecular vulnerability that some cancer cells rely on for survival.
For patients with certain blood cancers, particularly chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML), Venetoclax became an important new treatment option.
Its success also demonstrated something much broader: understanding the fundamental biology of cancer can reveal vulnerabilities that eventually become highly targeted therapies.
From a Laboratory Discovery to a Patient's Prescription
The scientists studying BCL-2 decades ago were not initially trying to create Venetoclax.
They were trying to understand a basic biological problem: how cells decide whether to live or die.
That work revealed BCL-2, helped unravel the biology of apoptosis and eventually made it possible to design drugs that could exploit this survival mechanism.
Years of further research and clinical development ultimately brought Venetoclax to patients.
Having spent many years at WEHI, I saw the later part of that story from inside a research institute. At the time, it was natural to think about Venetoclax in terms of experiments, clinical trials and research milestones.
Reading the experiences of patients and their families recently made me think about the other end of that journey.
Inside a research institute, Venetoclax can look like a remarkable example of successful translational research. Outside it, Venetoclax is something much more immediate: a medicine that a real person may see written on a prescription while they and the people around them wait and hope for the treatment to work.
A question about why cells refuse to die, asked in a Melbourne laboratory decades ago, eventually became the name of a medicine prescribed to patients.
For me, that is what makes the Venetoclax story so remarkable.
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