Right treatment, right person: precision medicine in action right now

This is happening right now at the University of Auckland for a team conducting research on cancer using the principles of precision medicine. Not only are they making discoveries, they are also able to apply this new knowledge in ways that are already benefiting patients.

“Precision medicine,” says Dr Michelle Wilson, medical oncologist and clinical director for cancer and blood research, “is about providing the right treatment for the right patient at the right time.

“We often call it ‘the great unknown’. We certainly know a lot more now than we did a couple of years ago, but every time we learn more, we discover more about what we don’t know. It’s an ever-evolving field and the patients are playing a vital role in creating the knowledge that drives that momentum.”

The multidisciplinary research team comprises physicians, clinicians, clinical trialists, biomathematicians, computer scientists, experts in genetics, genomics and bioinformatics, based in the University of Auckland and Te Whatu Ora Te Toka Tumai Auckland, both forming part of the Auckland Academic Health Alliance.

“It’s such a complex field that all of these are needed,” says Professor Print, who adds that an eminent team of this kind could not have been brought together without substantial funding at a level that ensures the continuity that allows for forward planning. These researchers would not be able to coordinate their investigations and sustain them at the required level of excellence without the generous enabling gift of $11 million from Lynne Erceg, augmented by smaller gifts from other generous donors.

“The team doesn’t just feel gratitude,” says Professor Print. “It’s much more than that. It’s the profound awareness that this support allows us to make new discoveries that are life-changing for New Zealanders and others all over the world.”

So what is precision medicine and how are the Auckland cancer researchers adding to the rapidly evolving pool of global knowledge?

There is one piece of knowledge that underlies it all.

“Cancer is caused by genetic mutation,” says Stefan Bohlander, Marijana Kumerich Chair in Leukaemia and Lymphoma Research in the Department of Molecular Medicine and Pathology. “Even when a virus triggers the cancer, what it sets in motion is a change in DNA.”

“So one important focus of our research is on identifying tumour cells and investigating their mutations, with the ultimate aim of developing treatment in the form of drugs that can target their vulnerabilities.”

Cancer researchers, when following the principles of precision medicine, use the patient’s genetic information to help guide their individual care and treatment – alongside a range of other data specific to that person.

An important part of the work, says Professor Bohlander, is to identify the patterns of mutation in the tumours of individual patients, in order to classify the cancer they have and choose the best treatment, including new drugs that target only cells carrying specific mutations, and not other cells.

A significant tool from the University of Auckland was developed here in 2019 and has been continually refined since then, with ongoing support from Lynne Erceg. This is the myeloid gene panel, now comprising 110 genes known to play a role in acute myeloid leukaemia (AML), a blood cancer with which 200 New Zealanders are diagnosed every year.

Another essential tool, used in cancer research centres all over the world and implemented in Auckland in 2022, is a similar gene panel comprising 500 genes that can guide the treatment of solid cancers such as melanoma, gynaecological, breast or lung cancers.

One of the most prominent success stories of precision medicine is the treatment of chronic myeloid leukaemia (CML), which is caused by a particular mutation and used to be invariably fatal. Now, with a one-pill-a-day treatment developed in the 1990s – which precisely targets this particular mutation – CML patients can expect to live normal life spans.

At the present time, with AML, another blood cancer still frequently fatal, notable progress is being made. AML, unlike CML, is associated not with just one but with multiple mutations, some of which are as yet unknown. The patient’s prognosis is strongly affected by which mutations are involved.

Haematologist Peter Browett, Professor of Pathology in the Department of Molecular Medicine and Pathology, says newly gained knowledge is already having an impact on the treatment of AML in ways that can lengthen, enhance or save patients’ lives.

“In almost every patient we can now identify ‘driver’ genes,” he says, “the mutations that are causing the leukaemia and driving the abnormal growth.”

“One of our research fellows has now analysed the first 100 AML patients, who have all received a precision mutation analysis using our myeloid gene panel. In 30 percent of patients we changed the prognostic group of the leukaemia and recommended changes to therapy based on those findings.

“Patients who perhaps were going to be treated with chemotherapy alone might be shown to have a molecular profile that predicts a high risk of relapse. That means we would look to do a stem-cell transplant early on, to have a higher chance of cure.”

Another focus in precision medicine is on our genetic heritage. Our inherited genes can make us more susceptible to particular cancers, influence our responses to anticancer drugs, or affect our reactions to their side effects. Knowing about these inherited genes can help clinicians make decisions about the best possible treatment for their particular patients.

For example, a brand-new piece of knowledge that has resulted from the myeloid gene panel analyses and is described by one researcher as having that “wow” factor – is that three to five percent of AML patients have inherited a gene from their parents that is associated with acute leukaemia.

This discovery is changing global thinking on AML. Not only does it throw into question a long-established belief – that AML has no hereditary component, apart from in a few rare paediatric conditions. It also suggests an immediate change in the way of selecting stem-cell donors: that close family members should not be chosen without undergoing tests to make sure they have not, themselves, inherited that gene.

One of the research team’s aspirations, which is being brought closer by advancing technology but would also require more research personnel, is to conduct genomic sequencing and interpretation of both the “normal” and cancer cells of every cancer patient that comes into their care.

Another is to ensure that Māori and Pākehā are partners in this field. This is already integrated into a range of clinical trials and studies in Auckland, such as a Māori Lung Cancer Cohort study, the Molecular Screening and Therapeutics (MoST) clinical trial and the Rakeiora Cancer Genomic Medicine Research Pathfinder Study.

Precision medicine is having a powerful impact on cancer research. It is also making its mark on other areas of medicine such as paediatrics, heart disease and ophthalmology, all of which have active research and clinical trials underway in Auckland.

New knowledge is being created and lives are changing as a result, which means the dream of the research teams is in action right now.