Analysis of the potential of Alpelisib in the treatment of lung cancer

Alpelisib(Alpelisib)-Piqray is an oral PI3Kα selective inhibitor, mainly used for patients with PIK3CA mutation-positive breast cancer. Its mechanism of action is to reduce the proliferation and survival ability of tumor cells by inhibiting the phosphatidylinositol 3-kinase (PI3K) signaling pathway. In recent years, with the in-depth understanding of the molecular characteristics of lung cancer, abnormalities in the PI3K pathway have also been found to be closely related to the occurrence, development and drug resistance of non-small cell lung cancer (NSCLC), which provides a theoretical basis and potential application direction for apelvis in the treatment of lung cancer.

Multiple prospective and retrospective analyzes have suggested that PI3KCA mutations exist in a certain proportion of non-small cell lung cancer patients, especially in subgroups with EGFR, KRAS mutations or drug resistance characteristics. This means that apelvis, as a small molecule inhibitor targeting the PI3K pathway, can theoretically exert an inhibitory effect on these patients. However, current clinical data in the field of lung cancer are still limited. Apelvis has not yet been officially approved for lung cancer indications, and its applications are mostly concentrated in clinical trials or early exploration stages.

In terms of combination treatment strategies, the potential synergy between apelvis and immune checkpoint inhibitors or EGFR inhibitors. Overseas preliminary studies have shown that inhibition of the PI3K pathway can affect the tumor microenvironment, including regulating immune cell infiltration and apoptosis sensitivity, which provides a biological basis for combination therapy. For patients with lung cancer, this strategy may show value in overcoming drug resistance and slowing disease progression.

It needs to be emphasized that the molecular heterogeneity of lung cancer patients is extremely high.PI3KCA mutation is only one of many potential driving factors. Therefore, the therapeutic effect of apelvis requires strict screening of the patient population. Overseas guidelines recommend that before participating in clinical trials, patients should undergo comprehensive molecular testing, including assessment of gene status such as PIK3CA, EGFR, and KRAS, to ensure the accuracy of the targeting strategy. At the same time, researchers are also concerned about the management of drug tolerance and adverse events, because PI3K inhibitors are often associated with hyperglycemia, rash, and gastrointestinal adverse reactions.

Reference materials:https://go.drugbank.com/drugs/DB12015