The Anti-Cancer Effect of Pitavastatin May Be a Drug-Specific Effect: Subgroup Analysis of the TOHO-LIP Study

Abstract

The significance of statin treatment for the reduction of cardiovascular (CV) disease has been reported, whereas other reports have also described anti-cancer properties associated with the class effect of statins. However, the differences in anti-cancer effect of various types of statins have rarely been examined. Pitavastatin is a statin with a different chemical structure and pharmacokinetics from other statins, and the mechanism of the specific anti-cancer effect of pitavastatin has been reported in in vivo therapeutic models. We previously revealed that pitavastatin therapy was superior to atorvastatin therapy in the prevention of CV events, despite similar LDL-cholesterol-lowering effect in the TOHO Lipid Intervention Trial Using Pitavastatin (TOHO-LIP). Furthermore, in subgroup analysis of the TOHO-LIP study, cumulative 240-week incidence of new cancer cases tended to be lower in the pitavastatin group compared to the atorvastatin group [0.32% (1/312) vs 1.94% (6/310), log-rank P=0.051]. This finding might reveal the superiority of pitavastatin to prevent carcinogenesis. The molecular mechanism by which pitavastatin suppresses the incidence of any-organ cancer is gradually elucidated, and new combination of cancer treatments with pitavastatin will be developed in the future to further enhance the anti-cancer activity and reduce the side effects.

Effect of concomitant use of pitavastatin with neoadjuvant chemotherapy protocols in breast cancer patients: A randomized controlled clinical trial

“…Pitavastatin was chosen rather than other statins due to its lipophilic nature, which enables its availability in extrahepatic tissues, and because its half-life is longer, which allows for the continuous inhibition of the targeted receptor (HMGCR) ( Catapano, 2010 , Barbalata et al, 2020 ). Pitavastatin has shown superiority over atorvastatin in preventing carcinogenesis ( Nagayama et al, 2021 ). In addition, although much higher doses of statins are usually needed to produce antitumor activities, hypercholesterolemia doses of both cerivastatin and pitavastatin can produce anti-cancer activity ( Jiang et al, 2014 ).…”

“…Although statins may have additive or synergistic effects with standard chemotherapy protocols ( Stryjkowska-Góra et al, 2015 ), its efficacy in combination with neoadjuvant regimens in patients with breast cancer has not yet been evaluated. Consequently, it is worthwhile to study whether statins can potentiate the tumor response of neoadjuvant breast cancer therapy, especially pitavastatin, which has shown superiority in reducing the incidence of cancer cases in comparison to atorvastatin ( Nagayama et al, 2021 ). This study aimed to evaluate the efficacy of pitavastatin as an adjuvant therapy added to neoadjuvant breast cancer therapy in patients with breast cancer in comparison to breast cancer patients who received only the neoadjuvant therapy.…”

Crosstalk between Statins and Cancer Prevention and Therapy: An Update

“…Otahal and his team proved that fluvastatin or pitavastatin combined with erlotinib led to apoptosis in human lung adenocarcinoma cells with a mutated or overexpressed epidermal growth factor receptor (EGFR) [38][39][40]. In cancer studies, it has been shown that statin use can significantly reduce mortality in women [41].…”

Pitavastatin induces caspase‐mediated apoptotic death through oxidative stress and DNA damage in combined with cisplatin in human cervical cancer cell line

“…Today, PITA has been found to be related to a reduction in the risk of cancer recurrence and mortality, and in combination with chemotherapeutic drugs, it has been found to be effective in overcoming resistance in resistant tumor cells. Therefore, there has been increased interest in PITA as a potential therapeutic agent for use in anti‐cancer therapy (Nagayama et al, 2021). Among the statins, PITA shows the strongest effect in reducing the viability of cancer cells in breast cancer and glioblastoma (Tilija Pun et al, 2022).…”

“…Therefore, there has been increased interest in PITA as a potential therapeutic agent for use in anti-cancer therapy (Nagayama et al, 2021). Among the statins, PITA shows the strongest effect in reducing the viability of cancer cells in breast cancer and glioblastoma (Tilija Pun et al, 2022).…”