Focused on the study of the mechanisms underlying the process of tumors metastasis development, the laboratory is involved in understanding what are the molecular, metabolic and functional alterations induced by drug therapy both on the cell and on the tumor microenvironment, and it is involved in understanding the consequences of drug therapy on cellular growth and metastasis development.
New preclinical metastatic models, derived from patient biopsies (PDX, Patient Derived Xenograft) were developed through the years in the laboratory in order to analyze new therapeutic strategies to be then translated in the clinical practice.
Of particular interest are combinations with angiogenesis inhibitors (drugs able to influence tumor vascularization), and/or new drugs able to negatively target specific cellular processes.
Ovarian and pancreatic adenocarcinoma: development of preclinical models to study new therapeutic approaches
First step toward the development of more effective therapies for patients is to demonstrate their "anticancer" activity in the preclinical setting. Among our goals one is to generate experimental models that mimic the complexity of the neoplastic pathology from an histopathological, molecular and pharmacological point of view: this point is particularly significant because our achievements could be then translate to the clinic (see Laboratory of Methodology for Clinical Research). Pancreatic Ductal adenocarcinoma (PDA), for example, transplanted in the murine pancreas is an excellent disease model to study tumor microenvironment response ( see Laboratory of Tumor Microenvironment). In the ovarian carcinoma, instead, the availability of preclinical models make able to mimic the neoplastic progression modalities, as in patients, characterized by the dissemination of tumor cells and the metastasis formation in the entire abdominal cavity, in order to ameliorate and improve all the therapies that contrast the disease progression.
Angiogenesis inhibitors in combination with novel therapies used in clinical practice
Ovarian carcinoma (OC) treatment with specific target therapies combination, such as Poly-ADP-Ribosylation inhibitors (PARPi) and angiogenesis inhibitors (AI), two emerging groups of drugs, aims to avoid side effects and the development of resistance to conventional therapy. Olaparib (PARPi) in combination with cediranib (AI) is investigated using ovarian carcinoma models, characterized by different mutational features and different sensibility to chemiotherapy, following modalities and schedules that could be easily translated also in clinical practice.
Inhibitors of " DNA damage recognition and repair" mechanisms in preclinical studies
Interfering with DNA repair mechanisms leads to tumor cell death. Our research uses tumor model platforms, in vivo, to study the activity of new pharmacological compounds able to inhibit the mechanisms of "recognition and repair" of DNA damage. In particular we aim to investigate their efficacy in combination with drugs generally used in clinical practice to identify combinations characterized by the best therapeutic index.
Analysis of metabolic changes induced by drug and associated to tumor progression
Although the reliable advantage obtained from angiogenesis inhibitors administered in combination with chemotherapy, patients afflicted by ovarian cancer often have to face with the recurrence of the disease (relapse). We examine how tumors malignancy and resistance to therapy is correlated to changes in cellular metabolism. This research provides us the basis to conceive new methods of therapeutic intervention capable of contrasting the clinical course of the disease (drugs that target the energetic metabolism of tumors cells).
Experimentation of drugs acting on tumor metabolism
The aim of the research is to evaluate the antitumor activity of compounds that impede cellular respiration, the real source of energy for many tumors and probably the metabolic process associated to tumor malignancy. A crucial part of the study concerns the identification of bio-markers, correlated to the therapeutic response, which will allow the identifications of patients who could most take advantage from these treatments.
Tumor microenvironment role in the cancer metastasis development
The interaction of the tumor cell with the microenvironment plays a crucial role in tumor malignancy. We investigate how perturbations of the host response and, more generally, of the microenvironment, following pharmacological treatments, influence the development of tumor metastasis and the onset of drug resistance, in the study of more effective therapeutic strategies.
International Consensus on Cardiopulmonary Resuscitation.