Hypoxia in Lung Cancer Management: A Translational Approach

Abstract

Lung cancer represents the first cause of death by cancer worldwide and remains a challenging public health issue. Hypoxia, as a relevant biomarker, has raised high expectations for clinical practice. Here, we review clinical and pathological features related to hypoxic lung tumours. Secondly, we expound on the main current techniques to evaluate hypoxic status in NSCLC focusing on positive emission tomography. We present existing alternative experimental approaches such as the examination of circulating markers and highlight the interest in non-invasive markers. Finally, we evaluate the relevance of investigating hypoxia in lung cancer management as a companion biomarker at various lung cancer stages. Hypoxia could support the identification of patients with higher risks of NSCLC. Moreover, the presence of hypoxia in treated tumours could help clinicians predict a worse prognosis for patients with resected NSCLC and may help identify patients who would benefit potentially from adjuvant therapies. Globally, the large quantity of translational data incites experimental and clinical studies to implement the characterisation of hypoxia in clinical NSCLC management.

Molecular Pathways and Key Genes Associated With Breast Width and Protein Content in White Striping and Wooden Breast Chicken Pectoral Muscle

“…In terms of cellular stress responses, the Cytohubba analysis also detected hub genes involved in the molecular response to hypoxia and oxidative stress conditions: the PRPF40A and THRAP3 genes. In fact, in the literature, it is reported that an over-expression of the PRPF40A gene is associated with an upregulation of biochemical pathways linked to hypoxia and oxidative stress conditions (Oleksiewicz et al, 2017), and it is reported that PRPF40A expression level could be considered a reliable marker of hypoxia-induced stress in human lung cancer (Huo et al, 2019;Ancel et al, 2021). Similarly, the protein encoded by THRAP3 has a role in the DNA repair process during oxidative stress events (Jungmichel et al, 2013;Vohhodina et al, 2017).…”

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

“…Association between presence of driver mutations and hypoxia levels in tumor cells within production of VEGF differs based on mutational type and localization. A link between factors related to hypoxia and circulating tumor DNA or miRNA was confirmed and can be potentially applied in clinical practice [79]. HIF-1α stimulates tumor neovascularization through involvement of VEGF family, within upregulation of matrix metalloproteinases secretion and higher activity of ERK1/2 pathway [80].…”

“…Cuccarese et al reported TAM infiltration differences based on cancer molecular type and hypoxia level [78]. Hypoxia-inducible factor 1α (HIF-1α), but also HIF-2α, angiopoietin-2 (Ang-2), fibroblast growth factor (FGF), and insulin-like growth factors (IGF) are involved in cancer progression (vimentin mediated EMT stimulation) and angiogenesis stimulation (VEGF upregulation) under hypoxia condition [79]. Hypoxia stimulates epithelial-mesenchymal polarization in lung cancer, promoting its higher aggressiveness and treatment resistance.…”

“…applied in clinical practice [79]. HIF-1α stimulates tumor neovascularization through involvement of VEGF family, within upregulation of matrix metalloproteinases secretion and higher activity of ERK1/2 pathway [80].…”

Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy

“…Hypoxia is also known to negatively influence treatment response to chemotherapy [ 27 ] and immunotherapy [ 20 , 28 ], as well as contributing to tumor aggressiveness [ 29 , 30 , 31 , 32 , 33 ]. A recent Special Issue in Cancers contained several original reports and contemporary review papers on the subject of tumor hypoxia [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. In this review, we will consider how thermal dose affects tumor hypoxia and, in turn, whether changes in hypoxia in response to thermoradiotherapy can influence treatment outcome.…”