“In this study, we investigated the therapeutic effects and underlying mechanisms of TAS-102 in combination with regorafenib against gastrointestinal cancers.”
BUFFALO, NY – July 9, 2024 – A new research paper has been published in Oncotarget Volume 15 July 2, 2024, titled “Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling, regardless of KRAS or BRAF mutation status” . “
TAS102 (trifluridine/tipiracil) monotherapy and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). Researchers have previously reported that regorafenib in combination with a fluoropyrimidine can delay disease progression in clinical case reports of patients with multidrug-resistant mCRC. In this new study, researchers Jun Zhang, Lanlan Zhou, Shuai Zhao, and Wafik S. El-Deiry from Fox Chase Cancer Center And Brown University hypothesized that the combination of TAS102 and regorafenib may be active in colorectal cancer and other gastrointestinal (GI) cancers and may in the future provide a treatment option for patients with advanced GI cancer.
“We investigated the therapeutic effect of TAS102 in combination with regorafenib in preclinical studies using cell culture, colosphere assays enriching for cancer stem cells and in vivo.”
TAS102 in combination with regorafenib exhibits synergistic activity against several gastrointestinal cancers in vitro, including colorectal and gastric cancer, but not against liver cancer cells. TAS102 inhibits colosphere formation and this effect is potentiated by regorafenib. The in vivo antitumor effects of TAS102 in combination with regorafenib appear to be due to antiproliferative effects, necrosis, and inhibition of angiogenesis.
Growth inhibition by TAS102 plus regorafenib occurs in xenografted tumors regardless of p53, KRAS, or BRAF mutations, although more potent tumor suppression was observed with wild-type p53. Regorafenib significantly inhibits TAS102-induced angiogenesis and microvascular density in xenografted tumors, as well as TAS102-induced ERK1/2 activation, regardless of RAS or BRAF status in vivo. TAS102 plus regorafenib is a synergistic drug combination in preclinical models of gastrointestinal cancer, with regorafenib suppressing TAS102-induced increases in microvascular density and p-ERK as contributing mechanisms.
“The drug combination TAS102 plus regorafenib could be further tested in gastric cancer and other gastrointestinal cancers.”
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28602
Correspondence to: Wafik S. El-Deiry
/Public dissemination. This content from the original organization/authors may be of a timely nature and edited for clarity, style, and length. Mirage.News takes no institutional position or bias, and all views, positions, and conclusions expressed herein are solely those of the author(s). See the full story here.