“DEPHENCE” system—a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer—a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies

Abstract

Ovarian cancer, especially high-grade serous type, is the most lethal gynecological malignancy. The lack of screening programs and the scarcity of symptomatology result in the late diagnosis in about 75% of affected women. Despite very demanding and aggressive surgical treatment, multiple-line chemotherapy regimens and both approved and clinically tested targeted therapies, the overall survival of patients is still unsatisfactory and disappointing. Research studies have recently brought some more understanding of the molecular diversity of the ovarian cancer, its unique intraperitoneal biology, the role of cancer stem cells, and the complexity of tumor microenvironment. There is a growing body of evidence that individualization of the treatment adjusted to the molecular and biochemical signature of the tumor as well as to the medical status of the patient should replace or supplement the foregoing therapy. In this review, we have proposed the principles of the novel regimen of the therapy that we called the “DEPHENCE” system, and we have extensively discussed the results of the studies focused on the ovarian cancer stem cells, other components of cancer metastatic niche, and, finally, clinical trials targeting these two environments. Through this, we have tried to present the evolving landscape of treatment options and put flesh on the experimental approach to attack the high-grade serous ovarian cancer multidirectionally, corresponding to the “DEPHENCE” system postulates.

Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer—The Possibility or the Necessity?

“…Based on the recent trends and achievements in the field of HGSTOC diversity, there is a need to create a novel complex personalized model of therapy. We have postulated the basic premises of such a model called "DEPHENCE" system [10]. During primary cytoreductive surgery, the samples of the primary tumor and peritoneal metastases are collected for the identification of genomic and/or epigenomic signatures.…”

“…The personalization of treatment should be understood as a proper treatment adjusted to the tumor type, tumor temporal heterogeneity, and genomic and/or metabolomic signature. Additionally, it should also mean that therapy fits key components of the tumor environment and the general and immunological status of the patient [10]. One of the most important tasks to personalize HGSTOC therapy is searching for individual tumor signatures that could differentiate therapy in a way that would enable the most effective tumor elimination.…”