The following is a summary of “Targeting Tumor Hypoxia Inhibits Aggressive Phenotype of Dedifferentiated Thyroid Cancer,” published in the February 2023 issue of Endocrinology & Metabolism by Ma, et al.

The occurrence of hypoxia, which is a lack of oxygen supply, is commonly seen in various types of aggressive cancers, but its role in the biology and treatment of dedifferentiated thyroid cancer (DDTC) was not well understood. Therefore, for a study, researchers aimed to clarify how hypoxia affects DDTC tumor biology.

Using transcriptome data from their center and a database, they established the link between hypoxia and dedifferentiation status, poor prognoses, and immune checkpoints in thyroid cancer. They also examined the impact of targeting hypoxia on anaplastic thyroid cancer (ATC) cells through in vitro and in vivo treatment with acriflavine (ACF) and investigated the connection between hypoxia and immunotherapy response in patients.

Their findings revealed that hypoxia score was positively linked with dedifferentiation status, and high hypoxia score was significantly correlated with reduced overall survival, TP53 mutation, and heightened expression of immunosuppression-related markers in DDTC. Treating thyroid cancer cells with ACF and siRNA targeting HIF-1α reduced the growth and proliferation of cells in vitro and in vivo, and lowered c-MYC and PDL1 expression in ATC. In addition, HIF-1α showed a positive correlation with PDL1 expression in DDTC. The researchers discovered that ACF’s target was related to differentiation genes and immune checkpoints via tumor-related kinases in ATC through an integrated phosphoproteome and RNA sequencing data analysis. Additionally, hypoxia score was associated with immunotherapeutic response in some cancer types.

In conclusion, the hypoxia score was a significant indicator of DDTC’s dedifferentiation status, prognoses, and immunotherapeutic response predicted by Tumor Immune Dysfunction and Exclusion. The study showed that targeting hypoxia using ACF can be beneficial in reducing the aggressive nature of ATC in a preclinical model of DDTC.

Reference: academic.oup.com/jcem/article-abstract/108/2/368/6747527?redirectedFrom=fulltext