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Effects of chemotherapy on secondary cancer risk and organotropism (International)

School of Medicine, Dentistry and Biomedical Sciences | PHD

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Funding
Funded
Reference Number
SMED-2231-1221
Application Deadline
None specified
Start Date
None specified

Overview

Triple Negative Breast Cancer (TNBC) has the highest rates of metastasis an extremely short life expectancy upon onset of secondary cancer, which is not curable. This project aims to understand the vulnerabilities that occur during aggressive treatment that can potentiate the risk for secondary cancer in these patients.

TNBC is treated primarily with neoadjuvant cytotoxic chemotherapy (before surgery); this is effective in reducing the primary tumour burden, but ineffective in preventing or treating secondary tumours. Interestingly, the location of TNBC metastasis (mostly brain and lung) resemble those of other aggressive and metastatic cancers (e.g., lung, melanoma), but not the remaining breast cancer subtypes, which metastasise less frequently and mostly to the bone, but for which there are less toxic and more targeted treatment options.
Chemotherapy is a systemic treatment that travels in the blood stream. We thus investigated how capillary (microvascular) endothelial cells isolated from different tissues responded to chemotherapy, and found that their responses are organ-specific. Changes in blood flow and vascular permeability impact on whole tissue function.

We hypothesise that the dose-dense chemotherapy administered to TNBC patients may be a risk factor for
developing secondary cancer. This project aims to investigate:
(1) how treatment-induced microvascular adaptations contribute to whole organ function and the formation of a pro-metastatic niche,
(2) what are the molecular regulators of vascular and tissue remodelling and
(3) to what extent endothelial cell responses to treatment contribute to frequency and location or metastatic tumours.

Funding Information

Project Summary
Supervisor

Dr Christina Branco

Research Profile


Mode of Study

Full-time: 3 Years


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