Pioneering studies of histone deacetylase inhibitors in myeloma: signals of activity set the stage for combination therapy trials

Prince, H.M.

doi:10.3109/10428194.2012.658571

Cited by 1 publication

(1 citation statement)

References 12 publications

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“…However, the clinical activity was modest as only a minority of patients showed a minimal response or disease stabilization (Table 3) [131,132,133,134,135]. Based on this, HDACi are now being tested in combination therapy with conventional agents (see Table 3 for more details) [136,137,138]. Phase I clinical studies using vorinostat in combination with bortezomib showed favorable tolerance and a good overall response in bortezomib-refractory patients [139,140,141].…”

Section: Hdaci and Dnmti In The Clinicmentioning

confidence: 99%

Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma

Maes

Valckenborgh

et al. 2013

Cancers

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Multiple myeloma (MM) is an incurable B-cell malignancy. Therefore, new targets and drugs are urgently needed to improve patient outcome. Epigenetic aberrations play a crucial role in development and progression in cancer, including MM. To target these aberrations, epigenetic modulating agents, such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), are under intense investigation in solid and hematological cancers. A clinical benefit of the use of these agents as single agents and in combination regimens has been suggested based on numerous studies in pre-clinical tumor models, including MM models. The mechanisms of action are not yet fully understood but appear to involve a combination of true epigenetic changes and cytotoxic actions. In addition, the interactions with the BM niche are also affected by epigenetic modulating agents that will further determine the in vivo efficacy and thus patient outcome. A better understanding of the molecular events underlying the anti-tumor activity of the epigenetic drugs will lead to more rational drug combinations. This review focuses on the involvement of epigenetic changes in MM pathogenesis and how the use of DNMTi and HDACi affect the myeloma tumor itself and its interactions with the microenvironment.

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