Ilaria Guccini receives Pfizer Research Prize in Oncology
The Pfizer Research Prize, one of the most prestigious in the field of medical research in Switzerland, has been awarded annually since 1992 in five different categories to young scientists conducting research at Swiss research institutes or hospitals. The award is aimed at outstanding contributions in basic or clinical research.
For “Oncology”, the prize was conferred to Dr. Ilaria Guccini, postdoc at the Institute of Molecular and Health Science.
Primary prostate carcinoma (PCa) is highly treatable, but metastatic PCa continues to be associated with deleterious effects and poses a very serious therapeutic challenge. Numerous stressors and conventional therapies, including chemotherapy, trigger a growth arrest in cells called cellular senescence also termed as "premature aging." Premature ageing in stressed/damaged cells at early stages prevents malignant transformation (cancer initiation): however, therapy-induced senescence in cancer cells prevents cancer progression and spread. Intriguingly, under certain conditions, ageing tumour cells do not become weaker over time but, paradoxically, they help tumors to become even more aggressive and resistant to chemotherapies. This is a phenomenon that has puzzled many cancer researchers for years.
Ilaria Guccini and Ajinkya Revandkar contemplated this unsolved problem. Their two core questions were: how come an anti-tumor process backfires and initiates metastasis which accounts for cancer-related deaths, and how can we prevent this process from getting started?
The two researchers and their collaborators discovered that the metalloproteinase-1 inhibitor, TIMP-1 plays a crucial role in the distinct outcomes of ageing of cancer cells .Loss of TIMP-1 in aged cancer cells triggers the reprogramming of the tumor microenvironment, resulting in the initiation of metastases, which does not occur in the presence of intra-tumoral TIMP1. Moreover, elimination of these prematurely aged TIMP-1-deficient cancer cells can block this process, which vouches for the senolytic therapy for the treatment of cancer. This "cancer cell aging mode", which is triggered by the tumor itself, therefore promotes metastases under certain circumstances. Simply put: if the TIMP-1 gene is or becomes silenced, senescent cancer cells get going again.
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