Cyclin-dependent kinases (CDKs) are an enzyme family that control cellular proliferation and growth. The interaction of CDKs with D-type cyclins results in the inactivation of retinoblastoma (Rb) tumor suppressor protein. Inhibiting the CDKs therefore allows the tumor suppressor to remain active.
Abemaciclib has previously demonstrated antitumor activity in HR+/HER2 metastatic breast cancer, renal cell carcinoma and several other solid tumor types. It’s been found to selectively inhibit CDK4 and CDK6. A recent study by Kosovec et al, further tests the potential of abemaciclib, this time for the treatment of esophageal adenocarcinoma (EAC).
The study evaluated several cell lines, monitoring apoptosis, proliferation, and pathway regulation during treatment with abemaciclib. Additionally, animals were induced to develop EAC and then treated with abemaciclib by intraperitoneal injection. The study was quite successful, the treated animals showed decreased tumor volumes and decreased prevalence of the disease altogether, while the treated cell lines showed increased apoptosis and decreased proliferation.
Overactive CDKs or inactive Rb protein are a common thread among several different cancer types, which makes CDK an interesting target of investigation for cancer treatments.
Kosovec JE, Zaidi AH, Omstead NA, et al. CDK4/6 dual inhibitor abemaciclib demonstrates compelling preclinical activity against esophageal adenocarcinoma: a novel therapeutic option for a deadly disease. Oncotarget. 2017 Nov 1;8(59):100421-100432. doi: 10.18632/oncotarget.22244.