Highlights of This Issue

Abstract

Although the role of HIF-1 in tumor progression is well characterized, the exact contribution of HIF-1 signaling to tumor radioresistance is not. Schwartz and colleagues leveraged high-resolution multimodality functional imaging of intact tumor xenografts to show that ischemic HIF-1 tumor signaling mediates downstream proangiogenic signaling responsible for the recovery of tumor blood supply following radiation treatment. Targeted HIF-1 blockade has the potential to provide clinically relevant radiosensitization through inhibition of a key mechanistic source for posttreatment stromal adaptation and tumor regrowth.TRAIL, a trigger of death receptor-induced apoptosis, is implicated in the clearance of disseminated tumor cells from the circulation. Despite promising results in animal models, current clinical work with TRAIL therapies suggests they require combination with sensitizing agents. The study by Phipps and coworkers shows that disruption of cell spreading can sensitize metastatic breast and melanoma cell lines to TRAIL-induced apoptosis in vitro. Disruption of signaling through β1 integrin, talin1, Src and MRTF-driven transcriptional control of the cytoskeleton all resulted in increased TRAIL killing. This work presents a range of targets that could be used to sensitize metastatic tumour cells to TRAIL therapies in vivo.According to previous studies, osteopontin (OPN) splicing isoforms show tumorspecific roles. To explore the role of OPN isoforms on ovarian carcinoma, Tilli and colleagues performed in vitro and in vivo functional assays using OvCaR-3 cell line. Among the 3 OPN isoforms, OPNc presented tumor-specific expression and specifically activated different features related to ovarian carcinoma tumor progression. OPNc features were mainly mediated by the PI3-K pro survival signaling, which is a crucial pathway in ovarian carcinoma progression. These results show promise for new therapeutic approaches for OC that selectively downregulate OPNc, altering its properties favoring ovarian carcinoma progression.Strategies to target functional activities of estrogen receptor (ER), prevalently abundant in the majority of breast cancers, fail in advanced stages of ER-independent, metastatic, drug-resistant cancer phenotypes. Sinha and coworkers developed the first estrogenic molecule (ESC8) that is nontoxic to normal cells while exhibiting anticancer activity in both ER(+/−) breast cancer cells. Mechanistically, ESC8 shows uncharacteristic PI3K/Aktassisted coinduction of apoptosis and autophagy in ER(−) breast cancer. Interfering with mTOR regulation, ESC8 induced autophagy for killing of cancer cells and prominently reduced mammary tumor growth. Together, ESC8 development strategized a novel concept of single drug chemotherapy for all stages of breast cancer.