Search

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-1a) 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-1a 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-1a 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Asiatic lions are found in the Gir Protected Areas and surrounding multi-use land matrices in Saurashtra, Gujarat. Scientifically monitoring their movement and activity is vital for their conservation management. We used GPS radio-collars to study the movement and activity of 19 individual lions. This pilot study's results revealed how technology-driven scientific monitoring can help in conserving endangered species. From the conservation management perspective, we discussed the use of virtual geofence functions and alert generation to reduce the chances of endangered species mortality on linear infrastructures. We also presented a pilot case study on how GPS radio-telemetry helped in securing the safety of dispersing sub-adult coalition males extensively moving in a multi-use land matrix. This study may help develop baseline ecological information for impact assessment studies and predictive models for lion ecological requirements, habitat improvement and proactive and retrofitting mitigation measures. Endangered Asiatic lions (Panthera leo persica) are found in the Asiatic Lion Landscape, Gujarat, which includes protected areas and a multi-use land matrix. Therefore, monitoring lions' space-use and spatio-temporal location is vital for managing various facets of human−lion interaction. Our study demonstrates how this was achieved by tracking lions using GPS radio-collars, triggering prompt action via an efficient communication network across political and forest administrative boundaries. We monitored the movement of 19 individual lions for 436.5 ± 32 days and also derived the mean daily activity from three-axis accelerometer-based activity-sensing feature of a radio-collar. We also monitored geofence breaches. We proposed that immobility and movement are two aspects that generate management action on the ground. While the movement is related to ranging and dispersal, immobility is a situation related to either the animal's feeding or its health status. From a management standpoint, we discussed the efficacy of the virtual geofence in preventing accidents when lions moved and also presented the advantages of being able to track dispersal through a case study of sub-adult lions. To strengthen our response to lion immobility, we developed a predictive model that specifically highlights an individual lion's health status and makes the alert response more precise. In conclusion, we critically reviewed the capabilities provided by GPS telemetry and provide protocols that help in the conservation management of lions and that will also have a wider application. [ABSTRACT FROM AUTHOR]