TITLE:
Biological Modulation of Parp Inhibition in Triple Negative Breast Cancer, a Combinational Approach Implementing Multitargeted Epigenetic Therapy (Mtet) with Parp Inhibition, in Advanced Breast Cancer: A Case Study
AUTHORS:
M. Nezami, Steve Hager, Julie Taguchi
KEYWORDS:
Triple Negative Breast Cancer, PARP Inhibition, Epigenetic Therapies
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.9 No.9,
September
11,
2018
ABSTRACT: The introduction of PARP inhibitors as active agents to inhibit the DNA repair
was a revolution in the cancer therapeutics, however, such
approach only has shown promising results for a short time in majority of cases
due to secondary mutations and promoter gene methylation, and most of patients
with triple negative breast cancer when treated with such agents only benefit
for a short time, until the tumor shows resistance and further the therapy fails [1]. Considering
this category of drugs and their mechanism of action in DNA repair [2] [3], several
recent studies have focused on combination of PARP inhibitors with chemotherapy,
immune therapy and interestingly relevant to this article, epigenetic therapies [4]. That said, to our knowledge the human data in this regard is missing.
Here we discuss a case report of a patient with stage four refractory and
resistant BRCA1 mutated triple negative breast cancer who responded in matter
of two weeks to a combinational therapy, consisting of PARP inhibitor and
epigenetic therapies. As the patient already had exhausted the PARP inhibitor
by excessive presence of BRCA positive altered circulatory DNA, the response
merely reflects the epigenetic therapy as back bone of treatment. The liquid
biopsy repeated after two weeks of combination therapy showed complete
disappearance (resolution of positive BRCA gene/c DNA), reflecting a synergism
by proposed modulation of resistance as mechanism of action. (The initial c DNA
showed 93 percent mutation allele fraction of BRCA gene.) To
our knowledge, this is the first study on combinational therapy in human. The finding
in this case could potentially change the standard of care in treating BRCA
positive tumors, by providing a superior treatment to current standards.