The potential of gas plasma technology for targeting breast cancer

Abstract

Despite therapeutic improvements in recent years, breast cancer remains an often fatal disease. In addition, breast cancer ulceration may occur during late stages, further complicating therapeutic or palliative interventions. In the past decade, a novel technology received significant attention in the medical field: gas plasma. This topical treatment relies on the partial ionization of gases that simultaneously produce a plethora of reactive oxygen and nitrogen species (ROS/RNS). Such local ROS/RNS overload inactivates tumour cells in a non-necrotic manner and was recently identified to induce immunogenic cancer cell death (ICD). ICD promotes dendritic cell maturation and amplifies antitumour immunity capable of targeting breast cancer metastases. Gas plasma technology was also shown to provide additive toxicity in combination with radio and chemotherapy and re-sensitized drug-resistant breast cancer cells. This work outlines the assets of gas plasma technology as a novel tool for targeting breast cancer by summarizing the action of plasma devices, the roles of ROS, signalling pathways, modes of cell death, combination therapies and immunological consequences of gas plasma exposure in breast cancer cells in vitro, in vivo, and in patient-derived microtissues ex vivo.

Keywords: ICD; ROS; adenocarcinoma; adjuvant therapy; immunogenic cell death; palliation; plasma medicine; reactive oxygen species.

FIGURE 1

Currently approved (blue) and experimental (red) treatment modalities for breast cancer treatment

FIGURE 2

Schematic of gas plasma tissue treatment and potential mediators and effectors

FIGURE 3

Illustration shows selected effects proven or hypothesized to be important in gas plasma‐mediated breast cancer cell demise

FIGURE 4

The cancer‐immunity cycle involves immunogenic cell death (ICD) and release of damage‐associated molecular patterns (DAMPs), spurring dendritic cell (DC) maturation and cognate antigen effector T‐cell activation and clonal expansion contributing to anticancer immunity. Gas plasma exposure is hypothesized to kick‐start this cycle, as shown in two published in vivo studies., The image is adapted based on established ICD concepts.,

FIGURE 5

Graphic illustrating the advantage of gas plasma treatment of tumour wounds or ulcerations