Evaluation of Prognostic Factors: From Breast Cancer to Bone Metastases

Overview

Bone metastases represent a frequent complication of some solid tumours, particularly prostate, breast and lung carcinomas. Bone metastases can cause pain and give rise to the so-called "Skeletal-related Events" (SRE) such as pathological fractures and nerve compression. Despite advances in cancer treatment in general, treatment options for bone metastases remain inadequate and generally palliative. It is therefore necessary to identify patients at "high risk" of developing metastases at an early stage of neoplastic disease in order to counteract it. Therefore, the identification of changes in the expression of proteins that could be variously involved in the progression of breast cancer is of primary importance since they could act as prognostic factors and therefore address the therapeutic strategy. The aim of the investigators is to clarify the role of de-regulation of post-translational events (such as SUMOylation) in the progression of breast cancer.

The most serious aspect of neoplastic disease is the spread of cancer cells to secondary sites, often distant from the primary site of growth. Bone is a breeding ground for many types of cancer, especially those derived from breast, prostate and lung. Despite the enormous progress in diagnosis and therapeutic strategies, bone metastases still have a profound impact on quality of life and survival, being often responsible for the outcome of the disease. To improve the outcome of patients with poor prognosis, a deep knowledge of the mechanisms underlying dissemination, colonization and progression of cancer cells in the bone is necessary. The investigators therefore intend to clarify some pathogenic mechanisms involved in the growth of bone metastases, and to uncover predictive signs that underlie the spread of breast cancer cells to bone. Primary aim of the investigators is to deepen the role of the de-regulation of post-translational events, such as Small Ubiquitin-like Modifier- (SUMO) SUMO-ylation in the progression of breast cancer. The expression of SENP1 (a member of the SUMO-specific protease family) in bone metastatic and non-metastatic mammary carcinomas will be evaluated. The evaluation of the expression of SENP1 in bone metastases will be finalised to define a possible use as a therapeutic target. SENP1 could be a potential prognostic indicator of the neoplastic progression of breast cancer and a potential therapeutic target, but data on its participation in the process of metastasis to bone are still scarce. Moreover, the investigators try to deepen the knowledge of the interaction between tumour cells and bone microenvironment and the role of immunosurveillance as an important part of the immune response against to neoplastic cells. Finally, the investigators will analyze the role of autophagy and apoptosis in the dissemination and growth of metastases due to the capacity of autophagy to provide energy, nutrients and resistance to anoikis, and to promote the dissemination of cancer cells and metastatic growth.