Li family grants boost cancer biomarker research

07 April 2016
Image of Dr Michelle Wilson
Dr Michelle Wilson

The first grants from the Li family’s $10 million cancer research gift to the University of Auckland, were made this week and will support research into cancer biomarkers.

In September last year, Auckland entrepreneur, Mr Liangren Li and his family, announced a record $10 million endowment fund to provide annual interest for investing in cancer research.

Mr Li was diagnosed with lung cancer in February 2015, despite never smoking, living a healthy lifestyle, and having none of the risk factors for lung cancer.

The major grant is the 2016 Li Family Cancer Research Project Grant which was made to Dr Michelle Wilson and her team, for a project called ‘PROSPER – Profiling of Oncology Patients as part of Clinical care and Research’.

The $480,000 project will run over three years starting in September 2016 and focusses on biomarkers for gynaecological cancers. It plans to expand to include other tumour types over this period.

The Li Family fund will also support the 2016 Li Family Cancer Research Postdoctoral Fellowship, awarded to Dr Yongchuan Gu for the research into ‘Targeted proteomics for profiling of predictive biomarkers in cancer therapy’.

Dr Gu is a researcher at the Auckland Cancer Society Research Centre (ACSRC) and the grant is for $300,000 over three years, starting in January 2017.

Dr Michelle Wilson, the principal Investigator for the PROSPER project, is a medical oncologist with the Cancer and Blood Service at Auckland City Hospital and a clinical senior research fellow with the Department of Oncology at the University of Auckland.

This project recognises that while substantial progress has been made in the treatment of cancer through the use of targeted therapies, what works for one patient might not work for another.

Biomarkers are specific characteristics of the cancer that may provide information about which cancers are more or less aggressive and which will or will not respond to a specific treatment.

“The increasing appreciation and identification of specific mutations that drive cancers, leaves us on the threshold of a new era in which biomarkers will be used to direct targeted agents to those patients most likely to respond,” says Dr Wilson.

The study will collect tumour samples from previous surgery alongside fresh samples if a cancer has recurred and analyse them to provide biomarker information specific to a patient's cancer.

This will help doctors identify which clinical trials or treatments may be appropriate for the patient in the future.

“Gynaecological cancers are a major cause of mortality and morbidity internationally,” she says. “In Auckland approximately 120 to 150 new patients with ovarian, endometrial or cervical cancer are seen by a medical oncologist each year.”

“In general, when these diseases recur, there are few effective therapeutic options with little improvement in patient outcomes over the past 20 years,” says Dr Wilson.

“Better therapeutic targets and treatments are an unmet need across these tumour types with treatment paradigms still based upon traditional platinum based therapy.”
PROSPER (Profiling of Oncology Patients as part of Clinical care and Research) will investigate the evolution of gynaecological cancers over time and in response to treatment to develop better biomarkers to guide treatment decisions and ultimately improve patient outcomes.

Biopsies at relapse will be collected and profiled with a 580 cancer gene panel. Circulating tumour DNA will also be collected and analysed alongside biopsies as a potential non-invasive alternative in the future.

“Linking genomic and clinical data will allow us to learn more about these diseases which will help us to challenge our current paradigm of care,” she says.

The four main objectives of the research are;
• To demonstrate that patients with gynaecological cancers can be matched to therapeutic targets, approved therapies and clinical trials of investigational agents based on the molecular profile of their tumours.
• To demonstrate the feasibility and acceptability of therapeutic selection guided by molecular pre-screening of fresh tumours collected at the time of disease relapse.
• To establish a clinical database in conjunction with genomic data.
• To establish ethically approved policies and procedures for collection of archival and fresh samples from patients with recurrent gynaecological cancers.

 

Image of Dr Yongchuan Gu
Dr Yongchuan Gu

Postdoctoral research by Dr Yongchuan Gu to apply targeted proteomics technology for profiling of predictive biomarkers in cancer therapy, will profile the determinants of Hypoxia Activated Prodrugs (HAP) sensitivity in human cancer cells, enabling evaluation of complex biomarker sets in cancer patients.

“Tumour hypoxia (results from a severely inadequate oxygen supply) confers resistance to many standard-of-care anti-cancer therapies,” says Dr Gu. “Hypoxia activated prodrugs (HAPs) provide a promising solution, but requires identifying tumours that are hypoxic, express prodrug-activating enzymes, and are intrinsically sensitive to the active drug.”

An innovative proteomic approach will be applied to profile the determinants of HAP sensitivity in human cancer cells, enabling evaluation of complex biomarker sets in cancer patients.

“This study will expand our understanding of how these determinants interact to affect tumour sensitivity to HAPs and find sub-types of tumours in which HAPs will be effective, ultimately to identify individual patients in a personalised medicine context,” he says.

Hypoxia is a ubiquitous feature of many tumours contributing to disease progression and treatment resistance, and thus represents a well-validated physiological target for cancer therapy.

Several hypoxia-activated prodrugs have been developed in the ACSRC at the University of Auckland, but further clinical development requires identifying tumours that are hypoxic, express prodrug-activating enzymes, and intrinsically sensitive to the activated drug.

“In this study, we will utilise a novel targeted (proteotypic peptide mass spectrometry) approach to identify candidate proteins as predictive biomarkers and profile biopsies of certain cancer types (such as head and neck and pancreatic cancers) through the recently-opened Auckland Regional Tissue Bank,” says Dr Gu.

“The information will be valuable not only for current drug development projects but also for building new capability in the Faculty of Medical and Health Sciences,” he says.

Further development of targeted proteomics technology through this project also offers opportunities for broader application in biomedical research in New Zealand.

Two doctoral scholarships were also awarded worth up to $27,000 each over three years.

 

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