Allosteric SHP2 inhibition enhances regorafenib's effectiveness in colorectal cancer treatment.
Biochem Biophys Res Commun
; 709: 149812, 2024 May 21.
Article
in En
| MEDLINE
| ID: mdl-38564942
ABSTRACT
Colorectal cancer (CRC) is the third most common cancer globally. Regorafenib, a multi-target kinase inhibitor, has been approved for treating metastatic colorectal cancer patients who have undergone at least two prior standard anti-cancer therapies. However, regorafenib efficacy as a single agent remains suboptimal. A promising target at the crossroads of multiple signaling pathways is the Src homology 2 domain-containing protein tyrosine phosphatase (SHP2). However, a combination approach using SHP2 inhibitors (SHP099) and anti-angiogenic drugs (Regorafenib) has not been reported in current research. In this study, we conducted in vitro experiments combining SHP099 and regorafenib and established an MC-38 colon cancer allograft mouse model. Our results revealed that co-treatment with SHP099 and regorafenib significantly inhibited cell viability and altered the biological characteristics of tumor cells compared with treatment alone in vitro. Furthermore, the combination strategy demonstrated superior therapeutic efficacy compared to monotherapy with either drug. This was evidenced by reduced tumor size, decreased proliferation, increased apoptosis, normalized tumor microvasculature, and improved antitumor immune response in vivo. These findings suggest that the combination of an SHP2 inhibitor and regorafenib is a promising therapeutic approach for patients with colorectal cancer.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colonic Neoplasms
/
Antineoplastic Agents
Limits:
Animals
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2024
Document type:
Article
Affiliation country:
China