Panobinostat: a review of trial results and future prospects in multiple myeloma

Abstract

Multiple myeloma is an incurable often devastating disease that is responsible for 1-2% of all cancers. Multiple myeloma is the second most common hematologic malignancy. Over the past two decades, advances in therapy have doubled life expectancy. Unfortunately, all patients ultimately relapse. Novel agents (immunomodulatory drugs and proteasome inhibitors) have changed the outlook for patients, but further breakthroughs are needed. Epigenetic treatments offer potential for advancing therapy by modifying oncogene responses. The acetylation status of various proteins can affect the availability of chromatin for transcription. This response may be modulated epigenetically to advantage using histone deacetylase inhibitors like panobinostat.

Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer

“…Clinical trials using HDAC inhibitors have been performed and their results indicate that HDAC inhibitors have antitumor activity (14,(36)(37)(38)(39)(40) and may be clinically beneficial. For example, SAHA/vorinostat and romidepsin were approved by the US Food and Drug Administration for the treatment of cutaneous T-cell lymphoma (36,37) and peripheral T-cell lymphoma (38) respectively.…”

“…For example, SAHA/vorinostat and romidepsin were approved by the US Food and Drug Administration for the treatment of cutaneous T-cell lymphoma (36,37) and peripheral T-cell lymphoma (38) respectively. In addition, panobinostat has demonstrated clinical success for the treatment of multiple myeloma (39). Today many inhibitors are being studied in advanced stages of clinical trials.…”

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises

“…Clinical trials (phases I and II) have also demonstrated that HDAC inhibitors result in minor adverse effects in patients (15,(26)(27)(28)(29)(30). Their mechanism of action involves binding of their hydroxamate group to the zinc cation (Zn 2+ ) located in the HDAC cavity (31).…”

“…For instance, the US Food and Drug Administration has approved SAHA and romidepsin as regimen of cutaneous T-cell lymphoma (29,31) and peripheral T-cell lymphoma (27) respectively. Moreover, panobinostat treatment is reported to be clinically successful against multiple myeloma (28).…”

Dinutuximab and Panobinostat

“…17 Panobinostat is extensively metabolized via reduction, hydrolysis, oxidation, and glucuronidation. 16,17 Name:…”