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Team

CANCAN

Challenge

Cachexia: Understand and reverse cachexia and declining performance status in cancer patients.

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Professor Eileen White

Professor Eileen White Team Lead

Deputy Director, Chief Scientific Officer, and Associate Director of Basic Research

CANCAN

Dr Marcus DaSilva Goncalves

Dr Marcus DaSilva Goncalves, Co-Team Lead

Assistant Professor of Medicine

CANCAN

Dr Tobias Janowitz

Dr Tobias Janowitz, Co-Team Lead

Assistant Professor 

CANCAN

INSTITUTIONS

14

LOCATIONS

UK, US

FUNDED BY

Cancer Research UK, National Cancer Institute

SPECIALISMS

oncology, metabolism, neuroendocrinology, immunology, preclinical modeling, clinical research, advocacy and more

The Cancer Cachexia Action Network

Funded by:

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Guided by the hypothesis that cachexia is a tumour-driven metabolic imbalance, the CANCAN team is exploring different pillars of basic research to understand the interconnected components of cachexia biology. These pillars are underpinned by a large clinical study to define clinical subtypes, towards the aim of developing individualised therapies.  

Many patients with advanced cancer experience cachexia, a debilitating wasting syndrome characterised by extensive weight loss from both skeletal muscle and fatty tissue, which can’t be reversed with nutritional therapy. Cachexia is often accompanied by fatigue, broad organ and tissue dysfunction, and a greatly diminished quality of life. In addition, cachexia limits patients’ ability to receive systemic cancer therapies and imparts a poor prognosis.  

Despite these major clinical implications, relatively little is known about cachexia, and effective therapies are lacking. Although cachexia’s major manifestation is muscular atrophy, the condition is now being understood to be a systemic phenomenon arising from a complex set of interactions between tumours and patients, through metabolism and the immune, endocrine and central nervous systems. 

A deep understanding of the mechanisms causing this syndrome would enable the development of novel interventions that could improve treatment response, quality of life and ultimately survival. The CANCAN team aims to expand the mechanistic understanding of cachexia and build a platform to develop therapeutic approaches that could reverse this debilitating condition.

Tackling the Cachexia Challenge

Cancer imposes a metabolic stress, diverting nutrients from patients to meet its high energy needs. The team believes that this metabolic imbalance causes cancer cachexia, and that the key to finding the first successful therapy to alleviate cachexia will be targeting the metabolic imbalance itself or its upstream mediators. 

The team is pursuing three pillars of basic research, underpinned by a large clinical study to define clinical subtypes.

  • Explore cancer cachexia as a systemic metabolic imbalance 

Cachexia is an amalgam of metabolic conditions that affect carbohydrate, fat, protein and energy metabolism. The team hypothesises that this metabolic imbalance is orchestrated by the tumour to favour its own metabolic demands at the expense of the patient.

Using preclinical models, the team will map how metabolism and nutrient distribution and utilisation change with cachexia progression. Additionally, they aim to identify the genes driving these changes, and explore dietary or pharmacologic strategies to rescue distinct metabolic imbalances.  

  • Identify tumour-secreted factors that drive cancer cachexia 

Tumour-secreted factors appear to strongly influence cancer cachexia development, although interactions between the tumour and its environment remain to be explored in cachexia. Central to this pillar is a comprehensive pipeline of target-discovery and validation models, from Drosophila and mouse models to the analysis of patient samples.

Data and biospecimens from TRACERx, a major Cancer Research UK-funded programme profiling patients’ progression from lung cancer diagnosis to cure or relapse, will enable the team to study cachexia development in people with early-stage cancer who have not yet received treatment through to people with later disease stages.  

  • Understand the how neuroendocrine dysregulation drives cancer cachexia by altering food intake and nutrient processing 

Systemic metabolism and food-intake behaviour are tightly regulated by the neuroendocrine system, in which the brain receives, integrates and orchestrates myriad signals to maintain energy homeostasis. Although cachexia cannot be reversed with nutritional therapy, patients experience major changes in energy balance, metabolism, hormone levels and sickness, including loss of appetite – this paradox in the context of weight loss is highly damaging yet poorly understood.  

Here, the team will develop a neuroendocrine atlas of cancer cachexia, to expand mechanistic knowledge of how hormones and cytokines drive metabolism and food-intake behaviour, and identify hormones that could be targeted as a novel treatment option.  

  • Integrating the pillars: identify distinct clinical subtypes of cancer cachexia 

The CANCAN team believes that cancer cachexia is not a single disease but rather has several diverse subtypes with differing biomedical and physiological characteristics – currently, all people with cancer cachexia are considered a homogeneous group.

The team will perform the largest multi-centre, longitudinal cohort study of its kind among patients at high risk for cachexia, collaborating with two of the largest healthcare networks in the US: Kaiser Permanente Northern California and the National Cancer Institute Community Oncology Research Program (NCORP) Research Base, an expansive community-based clinical-trial network. Through this cohort, the team hopes to identify and validate distinct cachexia subtypes and ultimately develop tailored therapeutic strategies for each disease subtype.  

Professor Eileen White

Professor Eileen White Team Lead

Deputy Director, Chief Scientific Officer, and Associate Director of Basic Research

We’ve assembled a team with diverse and complementary expertise, which we believe can advance the field of cachexia from this nascent, descriptive stage and find novel ways to remedy the condition.
Professor Eileen White
Dr Marcus DaSilva Goncalves
Dr Tobias Janowitz
Dr Bette Caan
Dr David Lewis
Dr Janelle Ayres
Professor Karen M Mustian
Professor Norbert Perrimon
Dr Sheng (Tony) Hui
Dr Steven B Heymsfield
Dr Giulia Biffi
Dr Mariam Jamal-Hanjani
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Dr Tony Coll
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Dave Chuter
Professor Sir Stephen O’Rahilly