Palbociclib’s mechanism of action

Palbociclib (Palbociclib) is a highly selective inhibitor of CDKs 4/6 and therefore blocks Rb phosphorylation, thereby inducing G1 arrest. Palbociclib-induced quiescence reduces the efficacy of DNA-damaging chemotherapy. Preclinical studies have shown that palbociclib enhances the efficacy of cytostatics, such as endocrine therapy or Her2-targeted therapy, but reduces the efficacy of cytotoxic chemotherapy.

An in vitro study of 45 breast cancer cell lines and 3 control mammary epithelial cell lines found that luminal HMR-positive and Her2-amplified cell lines were the most sensitive to growth inhibition by palbociclib. Synergistic effects, including the ability to enhance the sensitivity of tamoxifen-resistant cells, were observed when combined with tamoxifen or trastuzumab, respectively. Growth inhibition manifested as cell growth inhibition, and no lethality or apoptosis was observed. In contrast, an in vivo study of mouse breast cancer xenografts found that combining trastuzumab with carboplatin or doxorubicin reduced its antitumor activity compared with these cytotoxic drugs alone.

PalbociclibThe original drug has been launched in China and has been included in medical insurance. Currently, reimbursement is only available to patients who meet the indications. The common specifications100mg*21 pills may cost more than 6,000 yuan per box, while the original drug sold overseas is more expensive. The price of 125mg*21 pills per box may be around 10,000 yuan (the price may fluctuate due to exchange rates). Palbociclib generics are also sold overseas. The ingredients of the drug are basically the same as those sold domestically and abroad, but the price is cheap. For example, the price of a box of 125mg*21 tablets produced by a Bangladesh pharmaceutical factory may be several hundred yuan (the price may fluctuate due to the exchange rate).