Triple-negative breast cancer (TNBC) is one of the deadliest subtypes of breast cancer (BC) for its high aggressiveness, heterogeneity, and hypoxic nature. Based on biological and clinical observations the TNBC related mortality is very high worldwide. Emerging studies have clearly demonstrated that hypoxia regulates the critical metabolic, developmental, and survival pathways in TNBC, which include glycolysis and angiogenesis. Alterations to these pathways accelerate the cancer stem cells (CSCs) enrichment and immune escape, which further lead to tumor invasion, migration, and metastasis. Beside this, hypoxia also manipulates the epigenetic plasticity and DNA damage response (DDR) to syndicate TNBC survival and its progression. Hypoxia fundamentally creates the low oxygen condition responsible for the alteration in Hypoxia-Inducible Factor-1alpha (HIF-1α) signaling within the tumor microenvironment, allowing tumors to survive and making them resistant to various therapies. Therefore, there is an urgent need for society to establish target-based therapies that overcome the resistance and limitations of the current treatment plan for TNBC. In this review article, we have thoroughly discussed the plausible significance of HIF-1α as a target in various therapeutic regimens such as chemotherapy, radiotherapy, immunotherapy, anti-angiogenic therapy, adjuvant therapy photodynamic therapy, adoptive cell therapy, combination therapies, antibody drug conjugates and cancer vaccines. Further, we also reviewed here the intrinsic mechanism and existing issues in targeting HIF-1α while improvising the current therapeutic strategies. This review highlights and discusses the future perspectives and the major alternatives to overcome TNBC resistance by targeting hypoxia-induced signaling.

Colorectal cancer (CRC) represents the third most common cancer type worldwide and is a leading cause of cancer-related mortality in the US and Western countries. Rodent models have been invaluable to study the etiology of CRC and to test novel chemoprevention avenues. In the past, the laboratory mouse has become one of the best preclinical models for these studies due to the availability of genetic information for commonly used mouse strains with well-established and precise gene targeting and transgenic techniques. Well-established chemical mutagenesis technologies are also being used to develop mouse and rat models of CRC for prevention and treatment studies. In addition, xenotransplantation of cancer cell lines and patient derived xenografts (PDX) have been useful for preclinical prevention studies and drug development. This review focuses on the recent use of rodent models to evaluate the utility of novel strategies in the prevention of colon cancers including immune prevention approaches and the manipulation of the intestinal microbiota.