# Cold Atmospheric Pressure Plasma in Wound Healing and Cancer Treatment
## 3 CAP Application for Cancer Treatment  
Besides the tissue regenerating effects, CAP may also have detrimental effects on cells and tissues when prolonged treatment is performed, or higher intensities are applied [26]. This ability of CAP to inhibit cell proliferation and induce cell death prompted researchers to consider CAP as an innovative tool for cancer treatment. The growing interest in the potential use of CAP in oncology is represented by the increasing cumulative number of respective publications [27]. The vast majority of these studies were performed in vitro using cell cultures. For instance, an early study noted reduced viability and induced apoptosis in tumor cells after treatment with a plasma needle [28]. Adding to the large number of in vitro studies, a growing number of in vivo animal studies is supporting the potential use of CAP in cancer treatment. For instance, a study using a mouse model with induced tumors showed that in 66% of cases, the tumor completely regressed after CAP treatment, while untreated tumors in the control group kept growing continuously [29]. Another study reported a selectivity to ablate cancer cells using CAP, while the corresponding non-malignant cells remained unaffected [30]. Moreover, [PERSON] and colleagues have demonstrated that the plasma ROS chemistry can be optimized to maximize antitumor efficacy in vivo [31]. Whereas most studies assessed the use of CAP as a mono-therapy, some studies also demonstrate a beneficial effect of CAP as a combinatorial therapy, for example, in conjunction with the cytostatic drug gemcitabine [32]. In this study, mice were treated either with gemcitabine alone, CAP alone, or a combination of both and compared to an untreated control group. Analysis of the tumor weight 36 days after tumor induction and 12 days after the last treatment revealed a significant advantage of the combination therapy over each mono-therapy. While results from in vitro and in vivo animal studies are very encouraging, indicating a considerable potential of CAP in oncology, clinical studies are still very sparse. A review containing an overview of current literature on clinical studies assessing the use of CAP in oncology has been published recently [33]. This paragraph provides also provides a short overview of those few clinical studies. In a study that did not directly aim at using CAP for cancer treatment, CAP was used as part of multimodal therapy of mesothelioma with the goal of avoiding accidental translocation of malignant cells to the abdomen [20]. Within a median observation time of about one year, no relapse of the disease has been observed, and no vital tumor cells were detected in tissue specimens. A pilot study assessing the use of CAP to reduce the bacterial load on locally advanced head and neck cancers to reduce typical fetid odor accidentally also revealed partial tumor remission in some of the patients [21]. Subsequent studies by the group revealed comparable results and showed an increasing number of apoptotic cells in CAP treated tumor tissues compared to non-treated tissues [22; 24]. Total and partial remissions of actinic keratosis (precursor lesions of squamous cell carcinomas) after CAP treatment have been reported by two independent groups using different plasma devices [23; 25]. Details on patient numbers and treatment modalities of the here described studies are summarized in Tables 1 and 2, respectively.