BRCA1 foci test as a predictive biomarker of olaparib response in ovarian cancer patient-derived xenograft models.

Standard therapy for high-grade ovarian carcinoma includes surgery followed by platinum-based chemotherapy and poly-ADP ribose polymerase inhibitors (PARPis). Deficiency in homologous recombination repair (HRD) characterizes almost half of high-grade ovarian carcinomas and is due to genetic and epigenetic alterations in genes involved in HR repair, mainly and predicts response to PARPi. The academic and commercial tests set up to define the HRD status of the tumor rely on DNA sequencing analysis, while functional tests such as the RAD51 foci assay are currently under study, but have not been validated yet and are available for patients.

Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness.

In ovarian tumors, the omental microenvironment profoundly influences the behavior of cancer cells and sustains the acquisition of stem-like traits, with major impacts on tumor aggressiveness and relapse. Here, we leverage a patient-derived platform of organotypic cultures to study the crosstalk between the tumor microenvironment and ovarian cancer stem cells. We discovered that the pro-tumorigenic transcription factor FOXM1 is specifically induced by the microenvironment in ovarian cancer stem cells, through activation of FAK/YAP signaling.

Fibronectin fragments generated by pancreatic trypsin act as endogenous inhibitors of pancreatic tumor growth.

Background: The pancreatic microenvironment has a defensive role against cancer but it can acquire tumor-promoting properties triggered by multiple mechanisms including alterations in the equilibrium between proteases and their inhibitors. The identification of proteolytic events, targets and pathways would set the basis for the design of new therapeutic approaches.

Methods And Results: Here we demonstrate that spheroids isolated from human and murine healthy pancreas and co-transplanted orthotopically with pancreatic ductal adenocarcinoma (PDAC) in mouse pancreas inhibited tumor growth.

Chemotherapy-induced neutropenia elicits metastasis formation in mice by promoting proliferation of disseminated tumor cells.

Chemotherapy is the standard of care for most malignancies. Its tumor debulking effect in adjuvant or neoadjuvant settings is unquestionable, although secondary effects have been reported that paradoxically promote metastasis. Chemotherapy affects the hematopoietic precursors leading to myelosuppression, with neutropenia being the main hematological toxicity induced by cytotoxic therapy.