Abstract A122: Case review for multi-targeted epigenetic therapy ( MTET) and its rationale in an integrative approach

Abstract

Abstract In 2012 there were 11,957,599 advanced cancer cases in the US reported by CDC and the incidence has been almost unchanged over the previous 8 years (482,000 cases in 2000 versus 456,000 cases in 2008). There has been an annual percentage change of only (-0.6) between years 1999 to 2008 in cancer incidence. It is well described in the recent literature that epigenetic alterations are at least if not more important than genetic defects for the development and progression of malignant diseases. In the therapeutic field, transcriptional therapy is a very promising form of cancer treatment that is being extensively evaluated. It is speculated that inhibitors of DNA methylation and histone deacetylases can reactivate expression of tumor suppressor genes and induce histone hyperacetylation in the tumors of patients with solid cancers after treatment with these agents. Hypermethylation and transcription silencing of suppressor genes has been shown in 33% of breast cancers, 60% of prostate CA and 92% of colon CA. Although the value of such combination therapy both in chemoprevention, as well as treatment in patients with cancer is extremely important and can cause a significant shift in the current practice of oncology and cancer prevention, unfortunately, the results in clinical studies have been poor as the target histone hyperacetylation does not correlate with survival (possibly due to P 16/21 resistance, onco promoter mutations and unselectiveness of the therapies). To overcome such resistance we have developed a protocol using researched natural substances and off label drugs in a protocol called Multi targeted epigenetic therapy or MTET, currently tested in preclinical studies with promising results confirming apoptosis. This approach is shown to be clinically relevant in a set of cases treated and presented here. Here we present thirty cases of advanced resistant stage four disease that were treated through this method successfully with three samples cases to be described in details. We conclude that further research is warranted in a larger spectrum and in clinical trial setting to evaluate the efficacy of such method. Citation Format: Mohammad Nezami, Daniel Stobbe, Steven Hager. Case review for multi-targeted epigenetic therapy ( MTET) and its rationale in an integrative approach. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A122.