Palbociclib

Palbociclib was approved for marketing in the United States in February 2015. As the world's first approved CDK4/6 inhibitor, palbociclib has become the first-line therapy for HR+/HER2- breast cancer patients, and has been approved by more than 90 worldwide. Approved by the state for first-line and second-line treatment of HR+/HER2- breast cancer, it occupies most of the CDK4/6 inhibitor market.

Palbociclib in combination with endocrine disorders (such as letrozole, fulvestrant, etc.) has a very, very good effect on ER/PR-positive, HER2-negative breast cancer.

Cyclin D1 and CDK4/6 are downstream of signaling pathways that lead to cell proliferation. In vitro, Palbociclib reduced cell proliferation in estrogen receptor (ER)-positive breast cancer cell lines by preventing cells from entering the S phase of the cell cycle from the G1 phase. Combination treatment of breast cancer cell lines with palbociclib and an antiestrogen resulted in decreased retinoblastoma (Rb) protein phosphorylation, decreased E2F expression and signaling, and growth arrest compared with single agent use. In vitro treatment of ER-positive breast cancer cell lines with a combination of Palbociclib and an anti-estrogen increases cellular senescence compared to single-agent use for up to 6 days after discontinuation of Palbociclib, and cell growth if anti-estrogen therapy is continued The duration of aging. In vivo studies using a patient-derived ER-positive breast cancer xenograft model demonstrated that the combination of Palbociclib and letrozole increased inhibition of Rb phosphorylation, downstream signaling, and tumor growth compared with single-agent use.

In vitro, human bone marrow mononuclear cells treated with Palbociclib do not go senescence and resume proliferation after Palbociclib discontinuation in the presence or absence of antiestrogens.

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