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Hypoxia-induced therapy resistance: Available hypoxia-targeting strategies and current advances in head and neck cancer.

ABSTRACT: Most solid tumors, such as head and neck cancers, feature a hypoxic microenvironment due to angiogenic dysregulation and the consequent disruption of their vascular network. Such nutrient-deprived environment can induce genomic changes in several tumor cell populations, conferring survival and proliferative advantages to cancer cells through immunosuppression, metabolic switches and enhanced invasiveness. These transcriptional changes, together with the selective pressure hypoxia exerts on cancer cells, leads to the propagation of more aggressive and stress-resistant subpopulations increasing therapy resistance and worsening patient outcomes. Although extensive preclinical and clinical studies involving hypoxia-targeted drugs have been performed, most of these drugs have failed late-stage clinical trials and only a few have managed to be implemented in clinical practice. Here, we provide an overview of three main strategies to target tumor hypoxia: HIF-inhibitors, hypoxia-activated prodrugs and anti-angiogenic agents; summarizing the clinical advances that have been made over the last decade. Given that most hypoxia-targeted drugs seem to fail clinical trials because of insufficient drug delivery, combination with anti-angiogenic agents is proposed for the improvement of therapy response via vascular normalization and enhanced drug delivery. Furthermore, we suggest that using novel nanoparticle delivery strategies might further improve the selectivity and efficiency of hypoxia-targeted therapies and should therefore be taken into consideration for future therapeutic design. Lastly, recent findings point out the relevance that hypoxia-targeted therapy is likely to have in head and neck cancer as a chemo/radiotherapy sensitizer for treatment efficiency improvement.

SUBMITTER: Codony VL

PROVIDER: S-EPMC7814189 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Hypoxia-induced therapy resistance: Available hypoxia-targeting strategies and current advances in head and neck cancer.

Codony Victoria L VL Tavassoli Mahvash M

Translational oncology 20210116 3

Most solid tumors, such as head and neck cancers, feature a hypoxic microenvironment due to angiogenic dysregulation and the consequent disruption of their vascular network. Such nutrient-deprived environment can induce genomic changes in several tumor cell populations, conferring survival and proliferative advantages to cancer cells through immunosuppression, metabolic switches and enhanced invasiveness. These transcriptional changes, together with the selective pressure hypoxia exerts on cance ...[more]

PMID: 33465746

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Project description:Simple Summary The means of therapy in oncologic diseases have been developing continuously over the past years, intending to improve the overall survival and quality of life of affected patients. In head and neck oncology the surgical therapy is one of the key pillars in curative treatment. The standardized surgical techniques are supplemented and improved by the application of technical devices. The ambition is the reduction in peri- and postoperative morbidity, hospitalization time, and the enhancement of functional outcome. In other surgical specialties, the application of robotics is widely seen as standard. The purpose of this review is to outline the current status of robotics in head and neck surgery in the context of the present literature, to demonstrate reasonable application fields, and to discuss the expenditure of the usage of such tools. Furthermore, this review offers an overview of current research in this field. Abstract Background. In the past few years, surgical robots have recently entered the medical field, particularly in urology, gynecology, and general surgery. However, the clinical effectiveness and safety of robot-assisted surgery (RAS) in the field of head and neck surgery has not been clearly established. In this review, we evaluate to what extent RAS can potentially be applied in head and neck surgery, in which fields it is already daily routine and what advantages can be seen in comparison to conventional surgery. Data sources. For this purpose, we conducted a systematic review of trials published between 2000 and 2021, as well as currently ongoing trials registered in clinicaltrials.gov. The results were structured according to anatomical regions, for the topics “Costs,” “current clinical trials,” and “robotic research” we added separate sections for the sake of clarity. Results. Our findings show a lack of large-scale systematic randomized trials on the use of robots in head and neck surgery. Most studies include small case series or lack a control arm which enables a comparison with established standard procedures. Conclusion. The question of financial reimbursement is still not answered and the systems on the market still require some specific improvements for the use in head and neck surgery.

Dataset Information

Hypoxia-induced therapy resistance: Available hypoxia-targeting strategies and current advances in head and neck cancer.

Publications

Hypoxia-induced therapy resistance: Available hypoxia-targeting strategies and current advances in head and neck cancer.

Similar Datasets

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