Targeting cyclin-dependent kinase 9 by a novel inhibitor enhances radiosensitization and identifies Axl as a novel downstream target in esophageal adenocarcinoma


The cover for issue 45 of Oncotarget features Figure 7, "Overexpression of Axl enhanced radiosensitization by CDK9 inhibitors in esophageal adenocarcinoma cells," by Veeranki, et al.

The CDK9 inhibitor plus radiation significantly reduced growth of FLO-1, SKGT4, OE33, and radiation resistant OE33R xenografts and PDXs as compared to the cohorts treated with either single agent CDK9 inhibitor or radiation alone.

Axl protein expression in FLO-1 xenografts treated with combination of CDK9 inhibitor and radiation was significantly lower than the xenografts treated with radiation alone.

Clonogenic assay performed after overexpression of Axl in FLO-1 and SKGT4 cells enhanced radiosensitization by the CDK9 inhibitor, suggesting dependency of radiosensitization effects of the CDK9 inhibitor on Axl.

Figure 1: CDK9 inhibitor has potent radiosensitization efficacy in esophageal adenocarcinoma cells.

Dr. Dipen Maru said, "The incidence of adenocarcinoma of the esophagus and gastro esophageal junction has rapidly increased in the USA and other western countries over past 30 years."

In the last decade, advent of preoperative chemoradiation in neoadjuvant setting has improved patients survival and likelihood of complete surgical resection.

In spite of such aggressive therapeutic approach, 5-year survival for these patients is 20 30% ; primarily because of development of chemoradiation resistance and inability of chemoradiation to kill all tumor cells to achieve complete pathologic response.

The Maru research team concluded, "In summary, general failure of targeting CDK9 with pan-CDK inhibitors in clinics suggests that improved selectivity to CDK9 is the key to a successful development of CDK9 inhibitors as viable therapeutic agents."

Full text - https://doi.org/10.18632/oncotarget.27095

Correspondence to - Dipen Maru - [email protected]

Keywords - CDK 9 Inhibitor, esophageal adenocarcinoma, radiation, Axl

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