Study on the mechanism of action of pemetinib on tumor cell apoptosis and calreticulin exposure

Pemigatinib, as a small molecule kinase inhibitor targeting FGFR (fibroblast growth factor receptor), has shown significant efficacy in the treatment of malignant tumors such as cholangiocarcinoma. It blocks the growth and spread of tumor cells by specifically inhibiting the activity of FGFR.

Pemetinib blocks the activation of downstream signaling pathways by inhibiting the phosphorylation of FGFR. This results in the suppression of the expression of a series of genes related to tumor growth, survival, and apoptosis, thereby triggering the apoptotic process of tumor cells. Pemetinib can activate a series of apoptosis-related proteins, such as Caspase family members. These proteins play a key role in the apoptosis process, leading to cell death by cleaving key proteins within cells. It can also inhibit the activity of some anti-apoptotic proteins, such as Bcl-2 family members. These proteins normally protect cells from apoptotic signals, but the inhibitory effect of pemetinib makes tumor cells more susceptible to apoptosis.

According to a clinical study, a considerable number of patients with cholangiocarcinoma treated with pemetinib experienced tumor cell apoptosis, which shows that pemetinib has a significant effect in inducing tumor cell apoptosis.

Calreticulin is an important calcium ion-binding protein that plays a key role in maintaining intracellular calcium homeostasis. Pemetinib promotes calreticulin exposure during treatment. Specifically, pemetinib affects the permeability and stability of cell membranes, causing calreticulin to be released from intracellular to extracellular, where it can be recognized and attacked by the immune system.

This phenomenon of calreticulin exposure not only helps enhance the immune system's ability to kill tumor cells, but can also be used as a tumor marker to monitor the effect and prognosis of pemetinib treatment.