Tumour hypoxia sensor: A state of the art in oral cancer liquid biopsy

Oral squamous cell carcinoma (OSCC) is a top 10 global cancer with high mortality rates. Early detection via screening programs is crucial. Limited access to oral healthcare, especially in low- and middle-income countries, delays diagnoses, impacting survival rates. OSCCs exhibit rapid, unrestricted growth, leading to frequent hypoxic tissue regions. These hypoxic regions drive towards cancer progression and resistance to treatments like chemotherapy, radiotherapy, and immunotherapy. They also lead to dysfunctional blood vessel formation and encourage cells to become mobile and metastatic through epithelial-to-mesenchymal transition, ultimately leading to unfavourable outcomes. As hypoxia is found in 90% of solid tumours, it stands as a cancer hallmark. Assessing tumour hypoxia is complex due to varying oxygen levels among tissues, diverse tumour sizes, measurement techniques, and highly fluctuating tissue oxygenation, even within the same organ.^{1, 2} Cancer cells, with heightened proliferation and metabolism, demand substantial energy, but oxygen shortages exacerbate their hypoxic regions, altering metabolism. Hypoxia, common in solid tumours, indicates low tissue oxygenation (4−9%) and signifies poor prognosis in cancers like prostate, cervix, breast, and head and neck cancers.^{3, 4} Hypoxia prevalence varies by cancer type, generally affecting 30−60% of early-stage tumours.⁵ These percentages fluctuate based on tumour type, patient traits and assessment methods. Malignant solid tumours commonly experience lower oxygen levels than their tissue of origin. Recurrent tumours often display a higher hypoxic fraction than primaries.⁶ Early detection of hypoxia in cancer is pivotal, guiding tailored treatments for enhanced efficacy. Identifying it promptly allows targeted therapies to address hypoxia-related aggressiveness, potentially curbing tumour progression and bettering patient outcomes.⁷ While various methods detect tumour hypoxia, each bears limitations. Polarographic oxygen electrodes, the gold standard for accuracy, remain invasive and impractical for clinical use. Positron emission tomography (PET) offers non-invasive, detailed imaging but suffers from lower spatial resolution. Despite PET's sensitivity using radiotracer probes like 18F-FDG or 18F-FMISO, spatial limitations persist. Immunofluorescence and immunohistochemical methods indirectly assess hypoxia through protein expression but are confined to in vitro tissue evaluation. These techniques, though informative, are either invasive, limited in resolution, or confined to laboratory settings, hampering their widespread clinical utility.^8-10 Current cancer research indicates that exosomes (a subpopulation of extracellular vesicles) is a messenger of the hypoxic tumour microenvironment in oral cancer.^{11, 12} Exosome-based cancer sensors are also a smart initiative for precision cancer screening.¹³ An approved diagnostic tool is urgently needed to assess cancer hypoxia. This tool would aid in personalized hypoxia-focused therapies, improving outcomes. Evaluating tumour hypoxia is valuable for oncologists, surgeons and companies developing such treatments. Innovations like computer vision screening of hypoxia in circulating tumour cells (CTCs) are cutting-edge and could revolutionize cancer prognosis and therapies, potentially enhancing treatment precision and effectiveness. While tissue biopsy is the clinical gold standard for diagnostics, its invasiveness, cost, and limitations in capturing genetic variations within tumours as well as it's metastatic potenstial pose challenges. Biosensor hypoxia detectors emerge as an attractive alternative, particularly for long-term management and prognostication. Collecting easily accessible biological samples such as blood and saliva for early detection makes biosensors like this an appealing choice. Screening hypoxia with biosensors in CTCs via computer vision offers streamlined, cost-effective diagnostics with heightened accuracy, advancing cancer care. This method simplifies screening, improves precision and reduces healthcare expenses, revolutionizing personalized treatment approaches. Screening hypoxia in CTCs through biosensors and computer vision streamlines translational efforts, making it accessible and patient-friendly at healthcare centres.

Using biosensors and computer vision to screen hypoxia in CTCs benefits various healthcare settings, including hospitals, specialized cancer centres, research institutions and diagnostic labs. It aids in personalized treatment planning, supports hypoxia-targeted therapies in clinical trials, and facilitates precision medicine interventions for cancer patients based on their hypoxia status.

Sidhanti Nyahatkar-Manuscript writing; Divya Mirgh-Manuscript writing; Raman Muthusamy-Reviewing; Ketki Kalele-Final Reviewing and Editing.

The authors of this article declare no conflict of interest.

There is no funding for this study.

Not Applicable.