Summary
This PhD studentship at the Cancer Research UK Cambridge Institute focuses on understanding and unmasking the mechanisms of resistance to KRAS inhibition in pancreatic ductal adenocarcinoma (PDAC) across different genetic profiles. The project aims to identify both malignant cell-intrinsic and cell-extrinsic mechanisms, including fibroblast-mediated pathways, that contribute to therapy resistance. Using a combination of advanced models and techniques, the student will investigate how intra-tumour genetic heterogeneity influences treatment response and resistance.
PhD Studentship: Unmasking Mechanisms of Resistance to KRAS Inhibition Across Pancreatic Cancer Genetic Profiles
Designation
PhD Student
Table
| Category | Details | |
|---|---|---|
| Supervisor | Dr. Giulia Biffi | |
| Department/Location | Cancer Research UK Cambridge Institute | |
| Project Start Date | 1st October 2027 | |
| Application Deadline | 16th October 2026 | |
| Reference | SW51012 | |
| Job ID | 56988 |
Research Area
Pancreatic ductal adenocarcinoma (PDAC), KRAS inhibition, therapy resistance mechanisms, tumour microenvironment, cancer-associated fibroblasts, genetic heterogeneity, molecular biology, single-cell RNA sequencing, spatial transcriptomics, in vivo CRISPR, mouse models.
Location
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Eligibility/Qualification
Preferred Skills/Knowledge
- Motivation and enthusiasm for the project and a collaborative, hard-working laboratory environment.
- Commitment to complementary experimental strategies.
- Willingness to work with mouse models throughout the PhD is essential.
- Prior experience in a laboratory or industry research environment is required.
- Experience with tissue culture (cell lines and/or organoids), common laboratory techniques (e.g., immunohistochemistry, western blotting, PCR), and work with mouse models would be viewed favourably.
- Prior experience or knowledge of pancreatic cancer or cancer biology would be advantageous.
Eligibility
- Applications are welcome from both UK and overseas students.
Scholarship Description
Pancreatic ductal adenocarcinoma (PDAC) remains a significant clinical challenge. The recent development of KRAS inhibitors offers a promising therapeutic avenue, but rapid therapy resistance has been observed. This PhD project will investigate the mechanisms driving this resistance, focusing on how malignant-stromal crosstalk within defined genetic contexts contributes to distinct resistance pathways to KRAS inhibition. The project will leverage a panel of genetically heterogeneous PDAC models and combine techniques such as co-transplantation of organoids in mouse models, in vivo CRISPR, single-cell RNA sequencing, flow cytometry, multiplex immunofluorescence, spatial transcriptomics, and standard molecular biology approaches. A computational component may also be available depending on the student’s skills and interests. The research aims to define how intra-tumour genetic heterogeneity influences response and resistance to KRAS inhibition, complementing ongoing studies on inter-tumour genetic heterogeneity.
How to Apply
Please apply via the University Applicant Portal. Ensure you select to commence study in October 2027 and quote reference SW51012 on your application and in any correspondence.
Last Date for Apply
16th October 2026
Apply Link
https://www.postgraduate.study.cam.ac.uk/courses/directory/cvcrpdmsc
