Pathogenic mitochondrial DNA variants are associated with response to anti-VEGF therapy in ovarian cancer PDX models.

Background: Mitochondrial DNA (mtDNA) pathogenic variants have been reported in several solid tumors including ovarian cancer (OC), the most lethal gynecologic malignancy, and raised interest as they potentially induce mitochondrial dysfunction and rewiring of cellular metabolism. Despite advances in recent years, functional characterization of mtDNA variants in cancer and their possible modulation of drug response remain largely uncharted.

Methods: Here, we characterized mtDNA variants in OC patient derived xenografts (PDX) and investigated their impact on cancer cells at multiple levels.

Notch3-regulated microRNAs impair CXCR4-dependent maturation of thymocytes allowing maintenance and progression of T-ALL.

Malignant transformation of T-cell progenitors causes T-cell acute lymphoblastic leukemia (T-ALL), an aggressive childhood lymphoproliferative disorder. Activating mutations of Notch, Notch1 and Notch3, have been detected in T-ALL patients. In this study, we aimed to deeply characterize hyperactive Notch3-related pathways involved in T-cell dynamics within the thymus and bone marrow to propose these processes as an important step in facilitating the progression of T-ALL.

Antitumor Activity of the Xanthonoside XGAc in Triple-Negative Breast, Ovarian and Pancreatic Cancer by Inhibiting DNA Repair.

Dysregulation of the DNA damage response may contribute to the sensitization of cancer cells to DNA-targeting agents by impelling cell death. In fact, the inhibition of the DNA repair pathway is considered a promising anticancer therapeutic strategy, particularly in combination with standard-of-care agents. The xanthonoside XGAc was previously described as a potent inhibitor of cancer cell growth.

Targeting NOTCH1 in combination with antimetabolite drugs prolongs life span in relapsed pediatric and adult T-acute lymphoblastic leukemia xenografts.

T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic tumor, characterized by several genetic alterations, that constitutes 15% of pediatric and 25% of adult ALL. While with current therapeutic protocols children and adults' overall survival (OS) rates reach 85-90% and 40-50%, respectively, the outcome for both pediatric and adult T-ALL patients that relapse or are refractory to induction therapy, remains extremely poor, achieving around 25% OS for both patient groups. About 60% of T-ALL patients show increased NOTCH1 activity, due to activating NOTCH1 mutations or alterations in its ubiquitin ligase FBXW7.