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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Thursday, February 8, 2024
Based on the results of new research from French investigators, published in Cell Death & Disease, hypoxia-inducible factor (HIF) 1 may prove to be a potential therapeutic target in patients with non–small cell lung cancer (NSCLC), given its association with the downregulation of the Ras association domain family 1 isoform A (RASSF1A) gene and the activation of Yes-associated protein (YAP) in hypoxia. Furthermore, hypoxia leads to the overactivity of human nuclear Dbf2-related (NDR2) kinase in NSCLC, supporting brain metastasis formation.
“NDR2 expression [is] a useful biomarker to predict the risk [of metastasis] in patients with NSCLC,” stated Emmanuel Bergot, MD, PhD, of Normandie Université, Caen, France, and colleagues. In humans, “NDR2 is more expressed in metastatic NSCLC than [in] localized NSCLC.”
NDR2 overexpression may be easily and routinely measurable by immunohistochemistry on tumor specimens, the authors said. Additionally, “the pharmacological targeting of these new targets could be effective in preventing the spread of cancer and in improving the vital prognosis of patients with NSCLC.” The team’s hypothesis—which they believe was borne out by their results—was that a hypoxic tumor microenvironment might contribute to the inactivation of the RASSF1A/Hippo pathway during bronchial tumor growth, which would underlie the formation of brain metastases.
Disclosure: The study authors reported no conflicts of interest.
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