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Multikinase Inhibitor Shows Activity in Aggressive Subtype of Squamous Cell Carcinoma

By: Cordi Craig
Posted: Tuesday, May 21, 2019

For patients with an inherently aggressive subtype of squamous cell carcinoma, recessive dystrophic epidermolysis bullosa (RDEB), the multikinase inhibitor rigosertib may prove to be an effective therapeutic option, based on research findings published in Clinical Cancer Research. In fact, rigosertib effectively suppressed tumor growth and induced cancer cell death in all cases of cancer cells from 10 patients with RDEB while apparently not impacting healthy cells . Of several compounds studied, rigosertib had the highest specificity for cancerous cells of those with RDEB squamous cell carcinoma compared with normal skin cells.

“Rigosertinib was, by far, the best option,” noted Andrew P. South, PhD, of Thomas Jefferson University, Philadelphia, in a press release. “If we can reduce the cancer, or even reduce the spread of the cancer, that is going to improve patients’ quality of life and extend their lifespan.”

The authors isolated healthy and cancerous skin cells from 10 patients with RDEP squamous cell carcinoma. They tested the efficacy of six PLK1 inhibitors in lab cultures and performed preclinical mouse models of the disease.

In lab culture analyses, rigosertib induced apoptosis in all of the RDEB squamous cell carcinoma samples. The compound slowed the growth of healthy cells, but at a much higher concentration than required to kill cancer cells, which suggested a potentially lower risk of side effects. Rigosertib was also effective in mouse models, where systemic delivery of the disease inhibited cancer growth and tumor cells died.

“These data support a ‘first in RDEB’ phase II clinical trial of rigosertib [ClinicalTrials.gov identifier NCT03786237] to assess tumor targeting in patients with late-stage, metastatic, and/or unresectable [squamous cell carcinoma],” the investigators concluded.

Disclosure: The study authors’ disclosure information may be found at clincancerres.aacrjournals.org.



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