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Soo Park, MD
Soo Park, MD
Posted: Monday, April 15, 2024
For patients with melanoma or squamous cell carcinoma, decreasing the expression of autotaxin may be a potential therapeutic strategy to reduce disease progression, according to a preclinical research study published in Communications Biology. This decrease in autotaxin expression may be facilitated through the combined suppression of p190RhoGAP expression and inactivation of p110δ PI3K, suggested Evangelia A. Papakonstanti, MD, of the University of Crete, Heraklion, Greece, and colleagues.
“Here we show that the development and metastasis of melanoma and squamous cell carcinoma cancers can be blocked by a combined opposite targeting of RhoA and p110δ PI3K,” the researchers stated.
Male mouse models were used for all experiments. To monitor tumor growth, mice were randomly assigned to receive intratumoral injections of p190RhoGAP small-interfering RNA, intravenous injections of macrophages, or vehicle injection. Mice were administered p110δ or autotaxin inhibitors, and tumors were measured every 3 to 6 days. In addition, human melanoma samples were implanted into a separate group of mice and subsequently grafted into other mice until they were present in second- or third-generation rodents. Furthermore, blood samples were collected from mice to determine the extent of tumor cell burden and autotaxin activity.
The study authors reported that the genetic expression of inactivated p110δ seemed to be associated with a significant reduction in tumor burden. Moreover, tumor progression of melanoma and squamous cell carcinoma was significantly reduced after the deletion of p190RhoGAP. This deletion increased RhoA activity, which subsequently increased the activity of the tumor suppressor PTEN, which may explain the observed decrease in tumor progression, according to the study authors. These findings remained consistent regardless of whether or not tumors expressed BRAF V600E.
Disclosure: The study authors reported no conflicts of interest.
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