A Roadmap for the Success of Oncolytic Parvovirus-Based Anticancer Therapies.

Autonomous rodent protoparvoviruses (PVs) are promising anticancer agents due to their excellent safety profile, natural oncotropism, and oncosuppressive activities. Viral infection can trigger immunogenic cell death, activating the immune system against the tumor. However, the efficacy of this treatment in recent clinical trials is moderate compared with results seen in preclinical work. Various strategies have been employed to improve the anticancer activities of oncolytic PVs, including development of second-generation parvoviruses with enhanced oncolytic and immunostimulatory activities and rational combination of PVs with other therapies. Understanding the cellular factors involved in the PV life cycle is another important area of investigation. Indeed, these studies may lead to the identification of biomarkers that would allow a more personalized use of PV-based therapies. This review focuses on this work and the challenges that still need to be overcome to move PVs forward into clinical practice as an effective therapeutic option for cancer patients.

AECHL-1 targets breast cancer progression via inhibition of metastasis, prevention of EMT and suppression of Cancer Stem Cell characteristics.

Triple negative breast cancer (TNBC) features among the most aggressive manifestations of cancer due to its enhanced metastatic potential and immunity to therapeutics which target hormone receptors. Under such scenarios, anti-cancer compounds with an ability to influence multiple targets, or an entire process, will have an advantage over specific signal transduction inhibitors. To counter the metastatic threat it is essential to target cellular components central to the processes of cancer cell migration and adaptation. Our previous work on a novel triterpenoid, AECHL-1, explored its anti-cancer potential, and linked it to elevated ER stress in cancer cells, while its anti-angiogenic potential was credited for its ability to manipulate the cytoskeleton. Here, we broaden its range of action by showing that it curbs the metastatic ability of TNBC cells, both in vitro in MDA-MB-231 cell line and in vivo, in mouse models of metastasis. AECHL-1 does so by disrupting the cytoskeletal network, and also suppressing NF-κB and ß-Catenin mediated key molecular pathways. These activities also contributed to AECHL-1 mediated suppression of TGF-ß/TNF-α induced Epithelial to Mesenchymal Transition (EMT) and cancer stem cell characteristic. Thus, we present AECHL-1 as a promising therapeutic inhibitor of metastatic disease.