Identifying metabolic drivers of cachexia in colorectal cancer

Dr Johan Vande Voorde, Prof Campbell Roxburgh and Prof Owen Sansom

Lab: Metabolic Crosstalk in Cancer
Duration: 4 years, starting October 2025
Closing Date: Friday 30 May 2025

Background

Cancer cachexia is a wasting syndrome defined by ongoing loss of skeletal muscle and/or fat mass which cannot be restored by nutritional support. The condition severely impacts quality of life and the ability for patients to tolerate additional anticancer treatment. Cachexia is part of the common functional decline affecting 80% of advanced cancer patients and is responsible for an estimated 30% of cancer deaths. At present, there is no approved cure, and the underlying mechanisms of this debilitating condition are poorly understood.

The Cancer Research UK Scotland Institute specializes in research towards metabolic changes in cancer. We use state-of-the-art preclinical mouse models to identify metabolic programmes that may underly the onset or progression of cachexia in bowel cancer. The successful candidate will join a multidisciplinary team of cancer biologists and research-active clinicians. Using in vitro and in vivo experiments, we aim to identify metabolic regulators of cancer cachexia while also validating our findings in cancer patient cohorts. Ultimately, our goal is to develop new therapies for cancer cachexia.

Research Question

We will study systemic metabolic alterations which associate with cachexia in preclinical models of CRC and in CRC patients. A better understanding of these processes is critical for the development of effective therapies for this devastating disease.

Skills/Techniques that will be gained

The successful candidate will be trained in preclinical models of colorectal cancer and will work with patient data and samples to evaluate incidence of cachexia.

State-of-the-art metabolomics will be employed to study metabolic alterations in samples from in vitro and in vivo experiments, and from cancer patient cohorts. This will include both targeted and untargeted approaches using the liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry platforms available at the CRUK Scotland Institute.

Mechanistic studies will be performed using standard molecular biology techniques (e.g. qPCR, western blotting, etc.).

The successful candidate will be embedded in the research teams of Dr Johan Vande Voorde, Prof Campbell Roxburgh and Prof Owen Sansom. Furthermore, they will benefit from close interaction with other clinical and academic partners (including Prof Nigel Jamieson, Mr Ross Dolan, Dr David Sumpton and Dr Nesibe Peker).

For questions regarding the application process, PhD programme/studentships at the CRUK Scotland Institute or any other queries, please contact phdstudentships@crukscotlandinstitute.ac.uk.

Closing date: Friday 30 May 2025

Applications are open to all individuals irrespective of nationality or country of residence.

 APPLY HERE

Relevant Publications

1. Vande Voorde J, Steven RT, Najumudeen AK, Ford CA, Dexter A, Gonzalez-Fernandez A, Nikula CJ, Xiang Y, Ford L, Maneta Stavrakaki S, Gilroy K, Zeiger LB, Pennel K, Hatthakarnkul P, Elia EA, Nasif A, Murta T, Manoli E, Mason S, Gillespie M, Lannagan TRM, Vlahov N, Ridgway RA, Nixon C, Raven A, Mills M, Athineos D, Kanellos G, Nourse C, Gay DM, Hughes M, Burton A, Yan B, Sellers K, Wu V, De Ridder K, Shokry E, Huerta Uribe A, Clark W, Clark G, Kirschner K, Thienpont B, Li VSW, Maddocks ODK, Barry ST, Goodwin RJA, Kinross J, Edwards J, Yuneva MO, Sumpton D, Takats Z, Campbell AD, Bunch J, Sansom OJ. Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target. Nature Metabolism. 2023;10.1038/s42255-023-00857-0.
2. Najumudeen AK, Ceteci F, Fey SK, Hamm G, Steven RT, Hall H, Nikula CJ, Dexter A, Murta T, Race AM, Sumpton D, Vlahov N, Gay DM, Knight JRP, Jackstadt R, Leach JDG, Ridgway RA, Johnson ER, Nixon C, Hedley A, et al. The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nat Genet. 2021;53:16-26.
3. Flanagan DJ, Pentinmikko N, Luopajärvi K, Willis NJ, Gilroy K, Raven AP, McGarry L, Englund JI, Webb AT, Scharaw S, Nasreddin N, Hodder MC, Ridgway RA, Minnee E, Sphyris N, Gilchrist E, Najumudeen AK, Romagnolo B, Perret C, Williams AC, Clevers H, Nummela P, Lähde M, Alitalo K, Hietakangas V, Hedley A, Clark W, Nixon C, Kirschner K, Jones EY, Ristimäki A, Leedham SJ, Fish PV, Vincent JP, Katajisto P, Sansom OJ. NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. Nature. 2021;594(7863):430-435.
4. McMahon RK, O'Cathail SM, Steele CW, Nair HS, Platt JJ, McMillan DC, Horgan PG, Roxburgh CS. Circulating Markers of Systemic Inflammation, Measured After Completion of Neoadjuvant Therapy, Associate With Response in Locally Advanced Rectal Cancer. Dis Colon Rectum. 2025.
5. Dolan RD, Pennel K, Thompson J, McKenzie M, Alexander P, Richards C, Black D, Abbass T, Maka N, McGovern J, Roseweir A, McSorley ST, Horgan PG, Roxburgh C, McMillan DC, Edwards J. The relationship between tumour necrosis, systemic inflammation, body composition and survival in patients with colon cancer. BJC Rep. 2025 Feb 5;3(1):7.