A preclinical study conducted at the Institute of Oncology Research (IOR, affiliated with USI Università dellaSvizzera italiana) reveals the role of aging cells in metastasis formation and identifies the TIMP1 gene that can block it.
The findings by a group of scientists from Switzerland, Italy and the United States provide important information for personalized patient therapy. Most malignancies have the ability to form metastases, which are the cause of most deaths. The mechanisms responsible for the spread of cancer are still poorly understood.
Aging cancer cells stop multiplying. In cancer therapy, such a process is called cellular aging and is deliberately induced with drugs because it slows tumor growth. However, under certain conditions, these aging cancer cells can become more aggressive and form metastases that are undesirable in therapy.
An international team of scientists studying the aging processes of prostate cancer cells discovered that TIMP1 (tissue inhibitor of metalloproteinase type 1) is a key gene that determines the type of aging in prostate cancer and that metastasis formation can be blocked by eliminating the aging cells that promote this process.
If this gene is inactive or completely absent in patients, factors are released in the cancer cell that reprogram the aging cell making it more aggressive and invasive, which eventually forms metastases.
Based on clinical data and genetic testing of patients, researchers have shown that an inactive TIMP1 gene is common in men with prostate cancer and correlates with lack of response to chemotherapy and poor clinical outcomes. In light of this information and findings, new drugs that kill aging cells, so-called senolytic drugs, have been attempted on the premise that they may play a key role in halting the process. The results of these studies show the importance of personalized cancer therapy.
A patient’s genetic factors are critical in determining whether aging promotes prostate cancer metastasis or negatively stimulates tumor growth. In the latter case, careful administration of aging-inducing chemotherapeutic drugs is important. Instead, senolytic drugs that kill aging cells should be administered.
“This discovery could revolutionize the development of new drugs against aging cells reprogrammed to favor the formation of metastases “, says Dr. Ilaria Guccini, researcher.