Biology and Medicine

Retrospective Review of 374 Samples, Circulating DNA; As a Biomarker Assay to Support Clinical Management in Solid Tumors Treated with Multi Targeted Epigenetic Therapy (MTET)

Nezami M^1*, Klowsowski C² and Hager SJ^{3 1}Research Cancer Institutes of America, Sahel Oncology, Newport Beach, California, USA
²Guardant Health, Genomic Specialist, Medical Affairs, Redwood City, California, USA
³California Cancer Associates for Research and Excellence, Fresno, California, USA
^*Correspondence: Nezami M, Research Cancer Institutes of America, Sahel Oncology, Newport Beach, California, USA, Email:

Received: 07-Sep-2019 Published: 03-Oct-2019, DOI: 10.35248/0974-8369.20.12.462

Introduction

Our current understanding of cancer biology and the epigenetic science has transformed our ability to deliver therapies more precisely to the genetic and epigenetic targets driving the tumor growth and disrupting its behavior. In concert with our efforts to regulate the transcription of altered genes involved in tumor biology, we have emphasized a range of epigenetically regulated driver genes that control the tumor key molecular targets, involved with its growth and metastasis [1]. Statistical analysis on epigenetically driven targets had shown improved outcome compared to historical control [2].

Unfortunately epigenetic targets are dynamically expressed [3] and no single drug can clinically be used to target the epigenome as drugs have static mechanism of action. This limiting factor has caused researchers in the field to admit their failure in development of an epigenetic formula or product that has significant clinical impact in majority of cancer types, mainly solid tumors. As a result, the effort on epigenetic drug development has shifted in recent years to hematological cancers, such as lymphomas and leukemia where these drugs can make a difference in the clinic [4-13].

We earlier had shown that a combination of histone and DNA selective demethylators used in a specific protocol was able to significantly produce meaningful results in our experimental therapeutic models. Although cytotoxic therapies and targeted drugs have been studied in the recent years to correlate with such relevance, using liquid biopsy in different types of cancer, including lung [14-16], lymphoma [17], renal cancer [18], breast cancer [19-21], colon cancer [22-26], ovarian cancer [27,28], this is to our knowledge the first time this correlation with epigenetic drugs have been explored.

Materials and Methods

173 cases treated by MTET were collectively selected without selection bias. These cases were treated all in associated clinics of Medical centers of Hope.

The biomarker assays were performed through liquid biopsy through 374 samples. Amongst them 300 samples were positive for circulating DNA. 74 were negative. 66 patients had one sample and 63 patients had at least two samples (Tables 1 and 2).

Table 1: 374 samples sent through the end of May 2018 on 173 patients. More than 1/2 patients in the practice (61%) have had serial testing (2 or more G360 tests).

Table 2: Other and miscellaneous category.

Detection rate was 86 percent. The most and least common tumor types: 134 cases had breast cancer. 4 had glioblastoma. 20 cases carried BRCA alterations.

In average 64 percent of such cases were stage four and had no other viable options left.

Results

Serial monitoring of mutated allele fraction in circulating DNA analysis is feasible and clinically meaningful, when epigenetic drugs are applied in clinic and show positive clinical outcome based on such biomarker driven approach to epigenetic targets.

Further analysis as of April of 2019, for 491 cases is currently on going and preliminary findings are consistent with this article with common genetic mutations reflected in breast cancer responding to the epigenetic therapies. (Tables 3 and 4).

Table 3: Samples to date by cancer type, through end of April, 2019

Table 4: FGFR4436 Common gene mutations breast cancer samples (genes identified 10 or more times in breast cancer samples to date).

Conclusion

We conclude that such biomarker based epigenetic approach in cancer therapy could replace the current standard of care which is mainly blind shot and type specific.

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