Sorafenib improves the efficacy of rapamycin in the treatment of colorectal cancer

The activation of phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is closely related to the occurrence and metastasis of colorectal cancer. Mammalian target of rapamycin (mTOR) is an important serine/threonine protein kinase. The mTOR signaling pathway plays an important role by regulating cell cycle, protein synthesis and other pathways, and is at the center of growth regulation. In the link, its abnormal activity is related to the occurrence and development of malignant tumors.

mTOR is a downstream effector of the PI3K/Akt signaling pathway, which mainly regulates the occurrence and metastasis of colorectal cancer, suggesting that inhibition of mTOR may be one of the potential targets for the treatment of colorectal cancer.

Despite this, many cancers, including colorectal cancers, have demonstrated anti-tumor effects of rapamycin. In a study published in the journal Carcinogenesis, the researchers confirmed that rapamycin inhibits mTORC1, resulting in feedback activation of PI3K/Akt and RAS-MAPK signaling pathways, leading to the survival of tumor cells, which may be rapamycin resistant to colorectal cancer. One of the mechanisms of anti-tumor activity.

However, in combination with multi-kinase inhibitors such as sorafenib, rapamycin-induced activation of PI3K/Akt and RAS-MAPK signaling pathways was inhibited. Sorafenib combined with rapamycin to inhibit the proliferation of colorectal cancer cells.

Because of the mutations in KRAS and PIK3CA in colorectal cancer cells, they are not sensitive to rapamycin or sorafenib monotherapy, but they are very sensitive to the combination of rapamycin and sorafenib. Studies have shown that combination therapy can enhance the efficacy of rapamycin, induce colorectal cancer cell apoptosis and inhibit cell cycle progression, as well as migration and invasion. This study provided a basis for the combination of rapamycin and sorafenib in the treatment of colorectal cancer.