Biological Mechanisms Driving Early-Onset Colorectal Cancer
Dr Susanti Susanti, Dr Andrew Campbell and Professor Owen Sansom
Lab: Colorectal Cancer and Wnt Signalling
Duration: 4 years, starting October 2026
Closing Date: Monday 18 May 2026
Interviews for this position will take place in July 2026
Research Question
Colorectal cancer (CRC) is classically a disease of ageing, yet its most alarming contemporary trend is the accelerating incidence in young adults, termed early-onset CRC (EOCRC, diagnosed <50 years), which presents paradoxically with greater biological aggressiveness, higher metastatic rates, and inferior outcomes compared to later-onset disease. The biological mechanisms underpinning this age paradox remain poorly understood, but converging evidence implicates non-genetic risk factors, including diet, metabolic health, and lifestyle in reshaping the intestinal stem cell niche and tumour microenvironment (TME) in ways that may recapitulate hallmarks of an aged, tumour-permissive environment in young hosts. This project will exploit advanced genetically engineered mouse models (GEMMs) spanning young and aged animals under varying dietary and metabolic conditions to dissect how age and non-genetic exposures interact to shape tumour initiation and spread. Critically, these mechanistic findings will be anchored in human biology through interrogation of patient-derived organoids and clinical tissue cohorts from both UK and Indonesian EOCRC patients, enabling a uniquely powered, bidirectional translational framework that will identify the biological features that distinguish early-onset from later-onset CRC, and inform prevention and early intervention strategies.
Relevance to cancer challenges in Indonesia
Indonesia faces a particularly acute EOCRC burden, with an incidence approximately three times higher than in the UK, and young patients typically presenting with advanced-stage disease that carries high mortality. Despite this, Indonesian CRC patients remain dramatically underrepresented in global research, and the environmental, dietary, and biological drivers of this disproportionate incidence are unknown. This project directly addresses that gap: by integrating clinical tissue samples from Indonesian young-onset patients into the mechanistic study design, as a comparator to the UK cohort, the project will generate foundational data on whether EOCRC biology is shared or population-context-dependent across two distinct settings with different dietary patterns, gut microbiome composition, and genetic background. The results will provide the first molecular evidence base to support targeted CRC risk stratification and lifestyle-based prevention in Indonesian young adults, populations currently excluded from national screening programmes. The Indonesian PhD student will return with expertise in advanced cancer biology, translational research, and clinical cohort science that is critically needed to develop Indonesia’s biomedical research capacity. The findings will inform age-specific clinical management, evidence-based prevention strategies, and risk-stratified screening recommendations for young Indonesian CRC patients, while molecular signatures uncovered through cross-population tissue interrogation and patient-derived organoids hold potential to reveal novel diagnostic biomarkers and therapeutic targets translatable to the Indonesian healthcare setting.
Skills/Techniques that will be gained
Genetically engineered mouse models (GEMMs) and orthotopic models of intestinal cancer in young and aged animals under dietary and metabolic challenge, enabling direct comparison of tumour initiation, progression, and metastasis across age and exposure groups. Patient-derived organoid (PDO) cultures established from young-onset and later-onset CRC tissue to functionally interrogate whether EOCRC cells are intrinsically distinct in their response to microenvironmental stimuli identified by in vivo work. Multiplex immunohistochemistry, digital pathology, and spatial transcriptomics applied to clinical tissue cohorts from young-onset and later-onset CRC patients in both the UK (University of Glasgow) and Indonesia, enabling cross-population comparison of TME composition, immune infiltration, stem cell marker expression, and senescence-associated signalling as a function of age, metabolic status, and clinical outcome.
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: Monday 18 May 2026
For your application to be considered, you must upload your CV and a completed document CRUK-LPDP Recruitment Form(108 KB)
CRUK Recruitment Form Instructions
- We ask that you do not add your name or any Institution details to the document CRUK-LPDP Recruitment Form(108 KB) .
- Applications will be shortlisted by CRUK SI initially based on the document CRUK-LPDP Recruitment Form(108 KB) only. CVs will be used in further rounds of shortlisting to invite candidates to interview.
Relevant Publications
Susanti S et al. Molecular analysis of colorectal cancers suggests a high frequency of Lynch syndrome in Indonesia. Cancers. 2021;13(24).
Beyaz S et al. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2016;531:53–8.
Patel SG et al. The rising tide of early-onset colorectal cancer. Lancet Gastroenterol Hepatol. 2022;7(3):262–74.
Fane M, Weeraratna AT. How the ageing microenvironment influences tumour progression. Nat Rev Cancer. 2020;20(2):89–106.
Malla SB et al. Pathway level subtyping identifies a slow-cycling biological subtype with worse outcome in colorectal cancer. Nat Genet. 2024;56:458–72.
