Research projects

Understanding why treatment resistance develops

Researcher
Professor Lorenza Penengo
Project period
Jan 2022 - Jan 2025
Country
Research Institute
University of Zurich
Cancer types
General cancer research
Award amount
£250,484

Project aim

Professor Lorenza Penengo and her team are exploring a new molecular mechanism they recently discovered which could help explain why some patients treated with PARP inhibitors go on to develop resistance to chemotherapy. Their findings could lead to new ways to personalise cancer therapy and identify ways to overcome treatment resistance.

Hope for the future

People with genetic defects to BRCA genes are at a much higher risk of developing cancer – particularly breast, ovarian and prostate cancer. PARP inhibitors are a class of drug which have been developed to selectively target cancer cells with this genetic defect, when used in combination with chemotherapy.

Despite their success, many patients who initially respond to this combination treatment seem to go on to become resistance to chemotherapy. At this stage there are usually no options left for the patient so finding ways to overcome or prevent the development of resistance are crucial for stopping people dying from cancer.

Professor Lorenza Penengo and her team hope that their research will uncover the molecular detail behind why this resistance to chemotherapy develops and use this knowledge to start the development of ways to improve treatment for people with cancer.

Meet the scientist

Professor Penengo first became interested in cancer research during her PhD, having always been fascinated by nature and eager to learn how things really work. Outside of the lab, Professor Penengo likes to spend her time out in nature and by the sea as she loves to go diving and swimming.

The science

Tumours often increase the activity of a gene called ISG15, which plays a role in the immune system. Professor Lorenza Penengo and her team recently discovered that ISG15 makes cancer cells more sensitive to chemotherapy. However, further studies by the researchers also revealed that ISG15 must be activated in cancer cells for them to be fit and multiply. In short, ISG15 is needed for cancer cells to multiply but also makes them more sensitive to chemotherapy.

The research team believe this could help to explain why patients who are treated with chemotherapy, such as PARP inhibitors, develop resistance. They now want to try and understand exactly why the ISG15 gene helps cancer cells to multiply, with a particular focus on cancer cells with a BRCA gene mutation. Importantly, the researchers want to use this information to better understand the impact that this newly discovered mechanism has on the response to cancer therapy and the development of resistance.

The team hope that their findings will provide vital new information, which can be used to help personalise cancer therapy by developing ways to predict which patients will respond to treatment. Their work could also uncover molecular targets to help with the future development of new treatments for cancer.

The driving force behind our research is to try to ask important questions, the answers to which will help understand why things go wrong in cancer cells and advance cancer research.
Professor Lorenza Penengo

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