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Asenapine for use in cancer
PCT/EP2022/071374
The inventors have found that asenapine may be effectively used in the treatment of cancer. They have demonstrated its activity no only against several cancer cell lines in vitro, but also antitumorla effects in vivo. Asenapine is an atypical antipsychotic sold in the form of its maleate salt under the brand name Saphris, among others. It is used to treat schizophrenia and acute mania associated with bipolar disorder. Apart from the potential use of asenapine as monotherapy against cancer, asenapine may be advantageously used in combination with classical chemotherapeutic agents or other anticancer agents and provide an improved treatment thanks to a synergistic anticancer effect attained by the drug combination. In this regard, the inventors have found that combinations of asenapine with chemotherapeutic agents of different nature, such as cisplatin, carboplatin, and gemcitabine acted synergistically against cancer in vitro and in vivo.
Asenapine shows high affinity to the ligand survivin and, in particular, is able to specifically inhibit survivin protein levels. Currently, there are several survivin inhibitors under development, yet still no survivin specific anticancer agent has reached the market up to date. In fact, the most advanced survivin inhibitors, the survivin antisense oligonucleotide LY2181308, and the small molecule YM155, were discontinued after multiple clinical trials due to either low antitumor efficacy and/or over toxicity issues possibly due to insufficient target inhibition or selectivity. Asenapine has shown to be active against several cancer cell lines in vitro, but also in vivo; and it's safetly used in humans for another application.