A team of Australian scientists has become the first in the world to discover a way to target leukaemic cancer cells that are able to “hide’’ from chemotherapy and cause the cancer to relapse. Targeting these cells has the potential to cure leukaemias.
The team’s findings on using a process called “endocytosis inhibition” as a novel treatment for chemotherapy-resistant leukemia, were published in the prestigious journal Nature Communications this week (https://www.nature.com/articles/s41467-020-20091-6).
While traditional chemotherapy targets the cancer, it fails to kill certain leukaemic cells known as leukaemia stem cells and pre-leukaemia cells which can lead to the cancer relapsing in about 20 per cent of patients. These cells resist chemotherapy by hiding in safe microenvironments in the body and through their ability to self-renew, due to specific signalling pathways both on and inside these cells.
The new research reveals that leukemia’s self-renewal process can be blocked using compounds known as endocytosis inhibitors.
The team showed that treating chemotherapy-resistant leukaemia cells with traditional chemotherapy combined with an endocytosis-blocking novel inhibitor compound – led to leukemia stem cells and pre-leukaemia cells losing the ability to self-renew.
The cells no longer survived the chemotherapy treatment, and were unable to initiate tumour recurrence after treatment finished.
The research focused on chemotherapy-resistant T-Cell Lymphocytic Leukaemia (T-ALL) and Acute Myeloid Leukaemia (AML). The next step is to develop a version of the endocytosis inhibitor compound that will be safe and effective as a drug for human trials.
The team was led by Dr Cedric Tremblay from Monash University’s Australian Centre for Blood Diseases and the endocytosis inhibitor was designed by Professor Adam McCluskey from the University of Newcastle. Professor Phil Robinson from Children’s Medical Research Institute in Sydney who has been working in cell signalling for more than 25 years, was a co-author.
“Our strategy is shifting the paradigm in leukemia treatment and has the potential to reverse chemotherapy resistance and deliver significant benefits to patients,’’ Professor Robinson said.
He continued, “when leukaemia comes back, it is harder to stop – that is the problem we’re dealing with. This research shows that the cancer’s recurrence could be prevented by using these inhibitors combined with chemotherapy. It has really been transformative, but now we have to work out a way to deliver this in humans.”
The researchers also hope that using the two tools to fight cancer may reduce treatment time, which will improve patient well-being and save on health care costs.
“Does it reduce the time needed on chemotherapy? This is one of the questions we want to look at now’’ said Professor Robinson.
He is excited about the lessons this research could have for other conditions.
“This is such an important strategy that could apply to multiple disorders.”
His team is now interested in how blocking a broad array of cell signalling pathways by endocytosis inhibition could be applied to conditions such as epilepsy, neuropathic (nerve) pain and potentially as anti-viral drugs targeting HIV or the novel coronavirus that causes COVID-19.