What does the development of an embryo and cancer have in common? That was the introductory question award-winning UNSW Professor Chris Heeschen explored in his talk to enthusiastic UNSW alumni and interested community members at Customs House in Sydney this week.
After an introduction by UNSW Medicine Dean Professor Rodney Phillips, Professor Heeschen walked the audience through the mechanisms behind cancer development, pancreatic cancer and cancer stem cells, and went on to explain how novel approaches to fighting cancer stem cells could change the way we treat pancreatic cancer.
The ‘yin and yang of stem cells’
According to Professor Heeschen, there are many similarities between embryonic and cancer stem cells. Though our perception of embryo and cancer cells varies wildly, with one associated with the miracle of creation and the other a destructive menace, medical researchers have long found parallels between these two biological forces.
However, only recently it has been discovered that cancer is also driven by stem cells that are highly reminiscent of embryonic stem cells. So-called cancer stem cells in the tumour hijack signalling pathways from embryonic development and gain the ability to indefinitely and independently self-propagate.
“We are now developing strategies to combat these embryonic signalling pathways in cancer stem cells to prevent cancer from growing, but without affecting adult stem cells that are needed to keep our organs functioning,” Professor Heeschen said.
The human embryo is also very much prone to infection with Plasmodium, causing Embryonic Malaria, due to the expression of a specific protein during this stage of development. Intriguingly, cancer (stem) cells, but not normal cells in the adult body, also express these proteins.
“We use this mechanism to track ultra-rare cancer cells in the circulating blood of a patient, which could potentially allow us to detect cancer at a much earlier stage and provide better treatment options for our patients,” Professor Heeschen said.
Fighting cancer stem cells to prevent relapse
Professor Heeschen is adopting lessons from these similarities predominantly in the field of pancreatic cancer – one of the world’s deadliest cancers, with very low survival rates that haven’t changed for decades.
“There are two main types of chemotherapy for pancreatic cancer – but even when they work, most patients relapse at some point, so there is a dire need for new treatment approaches,” Professor Heeschen said.
What’s more, pancreatic cancer stem cells seem to be resistant to chemotherapy. The main goal of Professor Heeschen’s research, therefore, is to target cancer stem cells in a different way, so that relapse doesn’t happen. The team have already achieved this in mice.
“The most successful approach is likely going to be a combination between chemotherapy and specific targeting, where you’d treat the ‘normal’ tumour cells with chemotherapy, and cancer stem cells with genetic elimination,” Professor Heeschen explained.
The results would be better treatment, faster recovery, and a much higher survival rate in pancreatic cancer patients.
New mechanisms to help the body fight cancer
Professor Heeschen also explained how his work in cancer stem cells could help equip the body to fight back via its immune system.
In cancer patients, the immune system has given up on killing the cancer (stem) cells. Instead, cancer cells abuse the patient’s immune system to promote cancer progression. Re-engineering these immune cells could allow researchers to re-activate the body’s ability to fight the cancer (stem) cells.
“Novel, highly tuneable immune cells have the potential to cure patients from even the most aggressive cancer types, such as pancreatic cancer,” Professor Heeschen said.
“We call them ‘armed CAR T-cells’ – by manipulating T-cells, we teach them to attack cancer stem cells, so they’re essentially modified, educated immune cells that can attack tumours.”
Professor Heeschen is building his UNSW team and hopes to start human clinical trials of this new, precision immunotherapy approach by 2020.
About Professor Heeschen
Professor Heeschen was recruited to UNSW in 2018 via the Strategic Hires and Retention Pathway (SHARP). His group is dissecting the elements of cancer stem cells to develop more effective therapies for pancreatic cancer.
Professor Heeschen also has a strong track record in innovative, investigator-initiated clinical trials and has developed numerous biomarkers that have been successfully applied for precision medicine and implemented into clinical guidelines. Making use of his extensive international network of clinical investigators, industry partners and funding agencies, several innovative clinical trials have just been opened (SU2C and EU funded).
Professor Heeschen has published more than 150 articles in prestigious scientific journals such as the New England Journal of Medicine, Nature Medicine, The Lancet, Cancer Cell, Cell Stem Cell, the Journal of Experimental Medicine, and PNAS, among others. His work has been cited more than 26,000 times.
Professor Heeschen’s talk was part of UNSW Alumni’s Learn@Lunch event series. Learn@Lunch is a fast, easy-to-digest, one-hour session that offers alumni – and the wider community – the opportunity to foster lifelong learning.