An updated patent review on rational combinations of HDAC inhibitors for cancer chemotherapy (2020 – present): part 1-patent granted

INTRODUCTION: Tumor cell heterogeneity poses a challenge to monotherapy, as a single drug cannot kill all heterogeneous cancer cells of a tumor. The surviving cells may develop resistance, potentially leading to tumor recurrence. The combination therapy targets the disease through multiple mechanisms. Combinations of histone deacetylase (HDAC) inhibitor(s) with other inhibitor(s) have represented promising cancer chemotherapeutics by altering the epigenetic landscape of cancer cells by restoring acetylation and reactivating tumor suppressor genes, leading to cell cycle arrest, promoting apoptosis, and thus inhibiting cancer cell proliferation. AREAS COVERED: The patent literature (2020-present) on rational combinations of HDAC inhibitor(s) for cancer chemotherapy has been searched and reviewed from Google Patents, Patentscope, Espacenet, WIPO, and USPTO to provide an expert opinion on rational combinations for improved, optimized, and precise cancer therapy. This first part of a two-part review highlights the patent granted for the combination. EXPERT OPINION: The combination of HDAC inhibitors with other inhibitors, including Janus kinase (JAK), aurora kinase, tubulin, Sirtuin 2, and/or topoisomerase inhibitors, demonstrated a synergistic anti-cancer effect. Dual and multi-target inhibitors showed enhanced therapeutic efficacy in relapsed and refractory cases characterized by epigenetic dysregulation via histone modifications and alterations that contribute to disease progression.