Ricerc@Sapienza

Detection of pre neoplastic lesions of the breast has increased in the past years because of widespread screening programs and increasing numbers of biopsies.
Thus, understanding the molecular events underlying the development and progression of the lesions may help in solving the dilemma to balance the risk of causing unnecessary overtreatment or leaving an increased risk of recurrence or progression.
MiRNAs (miRs) are small non-coding RNA molecules that are key regulators of gene expression. Since their discovery, two decades ago, miRs research has gone through different phases from their discovery in the genomes, targets prediction and validation, characterization of their roles in disease, to exploring their therapeutic applications in numerous diseases.
MiRs are involved in numerous physiological cellular processes including development, differentiation, proliferation, apoptosis and stress response.
Most importantly, several evidences indicate that numerous miRs are aberrantly expressed in human cancers and their expression profiles can classify stage, subtype and prognosis of some cancer. In addition some of the innate properties of miRs make them highly attractive as potential biomarkers. MiRs can be readily detected in small volume samples using specific and sensitive quantitative real-time PCR (qRT-PCR); they have been isolated from most body fluids and are known to circulate in a highly stable, cell free form, and their unique expression patterns serve as ''fingerprints'' of various diseases.
Nevertheless the field of miRs in the precancerous lesions is still in the early stages and it requires large body of high-throughput specific experiments to generate sources of knowledge to better understand miRs mode-of-action from normal tissues to different stage of pre malignancy to the invasive carcinoma level.
We propose that by studying the miR molecular asset of these lesions it will be possible to predict/identify precociously which of those will progress towards invasive carcinoma. Early detection of cancer precursors would be highly clinically relevant toward the definition of more personalized management of the patients, sparing them unwanted surgery and sparing resources to the Regional and National Health System.
Overall this project, will lead to an immediate positive impact on patients' prognosis and survival and will provide all the participants involved in the cure of BC new important information regarding the management of the most frequent cancer in woman.
Significant advances have been made in the chemotherapeutic management of cancer. Unfortunately, more than 50% of all cancer patients either do not respond to initial therapy or experience relapse after an initial response to treatment and ultimately die from progressive metastatic disease. Even though the pharmaceutical industry has been successful in discovering many new cytotoxic drugs that can potentially be used for the treatment of cancer, this life-threatening disease still causes near 7 million deaths every year worldwide and the number is growing. Thus, the ongoing requirement to the design and discovery of new cancer therapy is urgent. In general, cancer chemotherapy is usually accompanied by severe side effects and acquired drug resistance. Therefore, the development of target therapy that will allow greater tumor specificity and less toxicity is the need of the hour. Recently, some attempts have been made for this purpose including the usage of monoclonal antibodies or small molecules to inhibit the tumor growth. Recent technological advances in development of targeted therapies using kinase inhibitors and monoclonal antibodies have paved the way for personalization of therapy in a growing segment of cancer patients. In cases where validated predictive biomarkers are available, administration of targeted therapies such as ALK inhibitors in NSCLC have been associated with unprecedented tumor response and clinical benefit. However, significant challenges remain, and curative interventions for advanced malignancies are extremely rare. Efforts to design tolerable combination therapies involving immune checkpoint and kinase inhibition are rational means of maximizing clinical benefit in the targeted delivery of anticancer therapies. These efforts can greatly benefit from appropriate patient selection based on molecular or immunohistochemical characterization of tumors and application of liquid biopsy techniques to supplement traditional disease classification schemes.