全额资助博士研究员：揭示不同胰腺癌遗传背景下对KRAS抑制的耐药机制
Fully-funded PhD studentship: Unmasking mechanisms of resistance to KRAS inhibition across pancreatic cancer genetic profiles
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AI 中文速览
- 研究内容
- 本项目旨在研究胰腺导管腺癌（PDAC）中细胞内在与外在对KRAS抑制的耐药机制（包括成纤维细胞介导的机制），研究将涵盖具有不同遗传背景的PDAC模型。项目将结合类器官小鼠模型共移植、体内CRISPR、单细胞RNA测序、流式细胞术、多重免疫荧光、空间转录组学及标准分子生物学方法，并可根据学生的技能和兴趣提供计算生物学相关内容。
- 申请条件
- 申请者需具备良好的科研热情、团队协作精神，并坚定承诺在整个博士期间配合进行基于小鼠模型的相关实验（willingness to work with mouse models throughout the PhD is essential）。要求具备实验室或工业研究环境的先前经验（Prior experience in a laboratory or industry research environment is required）。具备组织培养（细胞系或类器官）、常规实验室技术（免疫组化、蛋白质印迹或PCR）以及小鼠模型操作经验者将受到青睐，具备胰腺癌或癌症生物学背景/知识亦有优势。
- 待遇
- 全额资助的博士生名额（Fully-funded PhD studentship），入学时间为2027年10月1日。
- 申请方式
- 请通过剑桥大学申请者门户网站（University Applicant Portal）在线申请，选择2027年10月入学，并在申请及任何相关信件中注明参考编号SW51012。
由 gemini-2.5-flash-lite 生成，博士岗判定置信度 100%。
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- 导师
- Dr Giulia Biffi
- 来源
- The Chancellor, Masters, and Scholars of the University of Cambridge 官方招聘 · 最近核对 2026-10-10
- 详情核验
判定依据（原文摘录）
- 这是一项博士培养机会
Fully-funded PhD studentship: Unmasking mechanisms of resistance to KRAS inhibition across pancreatic cancer genetic profiles
- 欢迎英国及海外学生申请
We welcome applications from both UK and overseas students.
原文
Supervisor: Dr Giulia Biffi
Department/location: Cancer Research UK Cambridge Institute
Deadline for application: 16th October 2026
Course start date: 1st October 2027
Project details
For further information about the research group, including their most recent publications, please visit their website at https://biffilab.wordpress.com
Pancreatic ductal adenocarcinoma (PDAC) remains a formidable clinical challenge. A major recent advance has been the development of KRAS inhibitors, which have shown considerable promise in clinical trials (1). For decades, KRAS was considered undruggable; however, these new inhibitors represent a potential turning point for patients with PDAC. Despite this progress, rapid therapy resistance has already been observed in both patients and pre-clinical mouse models, highlighting the urgent need to define the mechanisms that drive resistance and to identify rational combination therapies.
In our laboratory, we have established and validated a panel of genetically heterogeneous PDAC models. These studies have shown that malignant-cell genetics shape distinct, therapeutically actionable vulnerabilities through both cell-intrinsic programmes and changes in the surrounding tumour microenvironment [(2) and unpublished]. These observations create an important opportunity: we hypothesise that malignant¿stromal crosstalk within defined genetic contexts drives distinct mechanisms of resistance to KRAS inhibition. In support of this, our work indicates that cancer-associated fibroblasts play diverse roles in PDAC progression and activate pathways that may contribute to therapy resistance (3, 4). This PhD project will therefore identify malignant cell-intrinsic and malignant cell-extrinsic mechanisms of resistance to KRAS inhibition, including fibroblast-mediated mechanisms, across genetically distinct PDACs. We will prioritise PDAC genotypes for which we already have preliminary data suggesting candidate mechanisms of resistance.
The project will combine complementary models and techniques, including 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 skills and interests of the student. Together, these strategies will define how intra-tumour genetic heterogeneity influences response and resistance to KRAS inhibition, complementing ongoing studies in the laboratory investigating inter-tumour genetic heterogeneity.
References/further reading
• Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer. N Engl J Med. 2026. (PMID: 42223072)
• SMAD4 and KRAS status shape malignant-stromal crosstalk in pancreatic cancer. Cancer Res. 2025. (PMID: 39841099)
• EGFR-activated myofibroblasts promote metastasis of pancreatic cancer. Cancer Cell. 2024. (PMID: 38157863)
• Functional heterogeneity of fibroblasts in primary tumours and metastases. Trends in Cancer. 2024. (PMID: 39674792)
Preferred skills/knowledge
We are looking for a motivated student who is excited by this project, enthusiastic about joining a collaborative and hard-working laboratory, and committed to the complementary experimental strategies required for its successful completion. As this project will rely heavily on mouse models, 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, including cell lines and/or organoids, common laboratory techniques such as immunohistochemistry, western blotting and/or PCR, and work with mouse models would be viewed favourably. Prior experience or knowledge of pancreatic cancer or cancer biology would also be advantageous.
Eligibility
We welcome applications from both UK and overseas students.
How to apply
Please apply via the University Applicant Portal at https://www.postgraduate.study.cam.ac.uk/courses/directory/cvcrpdmsc
You should select to commence study in October 2027.
Please quote reference SW51012 on your application and in any correspondence about this vacancy.
The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.
The University has a responsibility to ensure that all employees are eligible to live and work in the UK.