Sarcoma UK is investing in research leaders of the future. Our PhD programme aims to start a researcher’s career in sarcoma by funding a training fellowship which focuses on a hypothesis-driven research project.
This project is looking to unpick the cellular processes and behaviours which determine if a person will respond to chemotherapy. How cells signal to each other is thought to affect how they respond to treatment. Understanding these processes will allow clinicians to personalise medicine by identifying the patients who will respond to chemotherapy before treatment has started. If the patient is unlikely to respond, another drug may be considered or the patient can be spared the side effects of chemotherapy.
Deconstructing the sarcoma matrisome for drug target and biomarker discovery
The matrisome is the “glue” that exists between our cells. It provides supportive scaffolding and defines the structure of tissues. It has been shown that components of the matrisome provide signals to guide the behaviour of nearby cells. A number of studies indicate that these signals can also determine whether tumour cells respond to anti-cancer drugs. Variations in the makeup of the matrisome surrounding tumours may explain why some patients fail to respond to treatment.
Doxorubicin and/or Ifosfamide are standard-of-care chemotherapies used to treat sarcoma. However, a number of patients do not respond to such treatment, and many of those that initially respond later re-develop disease that shows resistance to these treatments. This research is aimed at discovering the matrisomal components that allow sarcomas to escape the anti-cancer effects of chemotherapy.
The experimental work in this project will investigate if the matrisome sends signals to soft tissue sarcoma cells to contribute to chemotherapy resistance. Using protein profiling of patient specimens will establish which components of the matrisome are responsible for drug resistance. Once identified, these molecular components can be modelled in sarcoma cell lines to study the biological processes regulating chemo resistance. The goal is to develop a way to identify which patients will respond to chemotherapy, and how best to prevent and treat drug resistance in sarcoma.