Blood cancers

Professor Andrew Zannettino: mapping the environment around dormant cancer cells

Challenge: can you describe this research project in 10 words?

Cancer relapse is caused by dormant cancer cells which are reactivated, in some cases many years after the primary tumour is thought to be cured.

What have you discovered in this area so far?

While most cancer patients respond to their initial therapy, many will relapse and succumb to their disease. To date, our studies suggest that relapse is a result of the reactivation of dormant cancer cells which can be found at sites distant from the primary tumour, such as the bone marrow. Dormant cells are resistant to chemotherapy and can persist in tissues for months, years or decades. Understanding what tissue-specific environmental cues are responsible for inducing and retaining these cancer cells in a “sleep like” state will allow us to target and eliminate these dormant cells and thereby minimise the risk of relapse. To date, we have developed intravital imaging techniques that have enabled us to study the fate of individual dormant tumour cells and showed that the endosteal niche (the inner surface of the bone) within the bone marrow, is pivotal in controlling dormancy of cancerous myeloma plasma cells. We have also demonstrated that these cells can be reactivated, re-sensitising them to chemotherapy, thus providing us with the ability to eradicate these cells and limit the risk of relapse.

What aspect of this research into cancer cell dormancy excites you the most?

Our team is uniquely positioned to discover new targets to drugs which be developed that will specifically eradicate dormant cancer cells. In addition, we will develop methods to detect dormant cancer cells and identify cancer patients who are at risk of relapse. Our connections with the global clinical research community and the pharmaceutical industry, will allow for rapid drug development and approval.

Down the track, what are the implications for patient care?

This research is likely to impact all cancer types where relapse is common and contributes to cancer death. As proof of concept, the team are focusing their efforts on eradicating dormant cells in the context of breast cancer and multiple myeloma.

How long might that take – from bench to bedside?

We have identified a dormancy associated gene “signature” from dormant myeloma plasma cells. This “signature” includes genes which encode cellular proteins which are expressed at the cancer cell surface allowing us to target them with either drug- or cell-based (CAR T-cell) therapies. While in their infancy, out team’s connections with the global clinical research community and the pharmaceutical industry will facilitate rapid drug development and approval. We anticipate that within 5-10 years, we will have developed a number of novel therapies which will reduce or eliminate the risk of disease relapse in many cancer settings.

What’s your Holy Grail – the one thing you’d like to achieve in your research career?

To understand what extrinsic (tissue environment) factors induce cancer cell dormancy. This will provide a means to eradicate dormant cells and limit the risk of cancer relapse, the major killer of cancer patients.

What is your biggest research hurdle?

While the proposed research is entirely feasible and supported by a team of world experts, the biggest hurdle facing this team is funding. This research addresses a Grand Challenge in cancer cure and only with appropriate levels of support will it be achievable.

Who has inspired you in work or life?

In my final year of school, my older brother Robert was diagnosed with cancer and succumbed to the disease 12 months later. This tragic event inspired my desire to become a cancer researcher and to play a small part in the global effort to rid the world of this terrible disease.

Any tips for sustaining work-life balance?

As a devoted husband and father of two young adult children, sustaining a work-life balance is a challenge. I have no real answers as to how to achieve this other than to live “in the moment” and throw myself 100% into everything you do. I love my work, I love my family and I love my hobbies (music, drives, theatre and movies).

Can you nominate a book that influenced you?

The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee is an inspiring read and entirely accessible to the lay reader. The book plots the history of cancer and discusses the contemporary approaches to treatment. A great read!!!

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