The SUPER-NEXT study to shine a light on unknown cancers

A study to genetically sequence patients with challenging cancers has received almost $5 million funding from the Australian Government’s Medical Research Future Fund Genomics Health Futures Mission to provide a clearer diagnosis and guidance for targeted, personalised treatment options.

Dr Richard Tothill The SUPER-NEXT study will use genomics to address the outstanding needs of patients with cancer of unknown primary (CUP) – a clinical conundrum where the origin of a cancer remains unknown despite extensive investigation.

University of Melbourne’s Dr Richard Tothill, based at the Centre for Cancer Research, is leading the study, which is the next phase in a long-standing collaboration with oncologist Associate Professor Linda Mileshkin at the Peter MacCallum Cancer Centre.

The SUPER-NEXT study will measure the clinical value of the ‘whole genome’ approach compared to contemporary methods analysing only a specific portion of the cancer genome. It will involve patients enrolled Australia-wide through a network of hospitals.

­­CUP has an exceptionally poor survival outcome with a historical one-year survival rate of only 25 per cent, and five-year survival of 14 per cent, making it one of the poorest survival cancer types in Australia.

With no understanding of cancer origin, Dr Tothill noted that patients are significantly disadvantaged in accessing effective and new therapies.

“These patients experience significantly greater psychological distress and a lower quality of life compared to people with known primary cancers.”

“Using whole genome sequencing we will identify mutational patterns, which can be used to inform diagnosis and treatment.

Dr Tothill said that the study will also be analysing DNA that is released from cancer cells into a patient’s blood, known as a ‘liquid biopsy’.

“Liquid biopsies have the potential to be faster and less invasive than conventional biopsies and allow analysis of a patient’s tumour where a tissue is deemed unsafe or difficult to obtain.”

The study will also investigate the use of a novel PET cancer imaging method to improve detection of a patient’s primary tumour, using genomics to predict which CUP patients may benefit from this new type of imaging.

SUPER-NEXT is the next phase of an Australia-wide CUP program called Solving Unknown Primary Cancer (SUPER), which started in 2014. A primary goal of SUPER-NEXT is to evaluate clinical whole genome sequencing to help resolve a tumour type diagnosis and improve therapeutic decision making in CUP. This is an expansion of an Australian Genomics ‘SUPER WGS’ Flagship project, which started in 2019.

The University of Melbourne has welcomed $9.5 million in total funding from the Medical Research Future Fund (MRFF) Genomics Health Futures Mission across three projects, including the SUPER-NEXT study.

University of Melbourne Deputy Vice-Chancellor (Research) Jim McCluskey said the funding will enable the University to continue vitally important genomics research.

“We thank Minister Hunt and the Federal Government for supporting genomics research which is critical in the detection and management of diseases,” Professor McCluskey said.

“I offer my congratulations to everyone involved in the projects that received a grant and acknowledge the achievements of the University’s precinct partners and affiliates.”