Correlation of circulating DNA (cDNA) alterations in several genes with established prognostic markers in a series of solid tumors treated with Multi Targeted Epigenetic therapy (MTET)

Abstract

In this article we review the dynamics of changes in the observed minor allele frequency fraction (MAF) as measured through circulating tumor DNA (ctDNA) of alterations in 8 target genes: NOTCH1, FGF2, MYC, RB1, ATM, MET, BRCA1, BRCA2, ATM, and VHL for which epigenetic dysregulation is identified in the literature to be most relevant to clinical response. We retrospectively examine a series of 54 oncology patients treated with multitargeted epigenetic therapy (MTET), a protocol used to treat solid tumors with epigenetically influenced driver genes. We examined the additional prognostic value of tracking such measurements of MAF with relation to their outcome, in the context of established survival markers including circulating tumor cells and PET imaging. In our cohort, observed levels of ctDNA changed rapidly marking it as a potential indicator for early molecular response. More than 50 percent reduction of ctDNA MAF and/or complete disappearance of CTC was used as major response after two weeks of the therapy. We concluded that molecular response identified in these 8 dysregulated genes, had independent prognostic value for outcome and could be used to generate further hypothesis in larger studies in solid tumors treated with this method. While previous research into the prognostic value of tracking ctDNA change has largely focused on specific cancer types or a specific gene, our study tracks several target genes over a variety of cancer types. *Correspondence to: MA Nezami, MD, President, Pacific Medical Center of Hope, Pacific Medical Center of Hope, Sahel Oncology, Fresno, CA, USA, E-mail: amnezami@yahoo.com