Electroporation is the process of instantaneously increasing the permeability of a cell membrane under a pulsed electric field. Depending on the parameters of the electric pulses and the target cell electrophysiological characteristics, electroporation can be either reversible or irreversible. Reversible electroporation facilitates the delivery of functional genetic materials or drugs to target cells, inducing cell death by apoptosis, mitotic catastrophe, or pseudoapoptosis; irreversible electroporation is an ablative technology which directly ablates a large amount of tissue without causing harmful thermal effects; electrotherapy using an electric field can induce cell apoptosis without any aggressive invasion. Reversible and irreversible electroporation can also activate systemic antitumor immune response and enhance the efficacy of immunotherapy. In this review, we discuss recent progress related to electroporation, and summarize its latest applications. Further, we discuss the synergistic effects of electroporation-related therapies and immunotherapy. We also propose perspectives for further investigating electroporation and immunotherapy in cancer treatment.

Background: H3^K27M mutated diffuse midline gliomas (DMGs) are extremely aggressive and the leading cause of cancer‐related deaths in pediatric brain tumors with 5‐year survival <1%. Radiotherapy is the only established adjuvant treatment of H3^K27M DMGs; however, the radio‐resistance is commonly observed.Methods: We summarized current understandings of the molecular responses of H3^K27M DMGs to radiotherapy and provide crucial insights into current advances in radiosensitivity enhancement.Results: Ionizing radiation (IR) can mainly inhibit tumor cell growth by inducing DNA damage regulated by the cell cycle checkpoints and DNA damage repair (DDR) system. In H3K27M DMGs, the aberrant genetic and epigenetic changes, stemness genotype, and epithelial‐mesenchymal transition (EMT) disrupt the cell cycle checkpoints and DDR system by altering the associated regulatory signaling pathways, which leads to the development of radio‐resistance.Conclusions: The advances in mechanisms of radio‐resistance in H3^K27M DMGs promote the potential targets to enhance the sensitivity to radiotherapy.

Investigate whether rAAV‐anginex gene therapy combined with radiotherapy could decrease growth and pulmonary metastasis of osteosarcoma in mice and examine the mechanisms involved in this therapeutic strategy. During in vitro experiment, multiple treatment regimes (rAAV‐eGFP, radiotherapy, rAAV‐anginex, combination therapy) were applied to determine effects on proliferation of endothelial cells (ECs) and G‐292 osteosarcoma cells. During in vivo analysis, the same multiple treatment regimes were applied to osteosarcoma tumor‐bearing mice. Use microcomputed tomography to evaluate tumor size. Eight weeks after tumor cell inoculation, immunohistochemistry was used to assess the therapeutic efficacy according to microvessel density (MVD), proliferating cell nuclear antigen (PCNA), and terminal‐deoxynucleotidyl transferase‐mediated nick‐end labeling (TUNEL) assays. Metastasis of lungs was also evaluated by measuring number of metastatic nodules and wet weight of metastases. The proliferation of ECs and the tumor volumes in combination therapy group were inhibited more effectively than the other three groups at end point (P < 0.05). Cell clone assay showed anginex had radiosensitization effect on ECs. Immunohistochemistry showed tumors from mice treated with combination therapy exhibited the lowest MVD and proliferation rate, with highest apoptosis rate, as confirmed by IHC staining for CD34 and PCNA and TUNEL assays (P < 0.05). Combination therapy also induced the fewest metastatic nodules and lowest wet weights of the lungs (P < 0.05). rAAV‐anginex combined with radiotherapy induced apoptosis of osteosarcoma cells and inhibited tumor growth and pulmonary metastasis on the experimental osteosarcoma models. We conclude that the primary mechanism of this process may be due to sensitizing effect of anginex to radiotherapy.

Background: Besides the hallmark of H3K27M mutation, aberrant amplifications of receptor tyrosine kinases (RTKs) are commonly observed in diffuse midline glioma (DMG), a highly malignant brain tumor with dismal prognosis. Here, we intended to evaluate the efficacy and safety of a multitarget RTK inhibitor anlotinib in patients with H3K27M‐DMG.Methods: A total of 40 newly diagnosed H3K27M‐DMG patients including 15 with anlotinib and 25 without anlotinib treatment were retrospectively enrolled in this cohort. Progression‐free survival (PFS), overall survival (OS), and toxicities were assessed and compared.Results: The median PFS and OS of all patients in this cohort were 8.5 months (95% CI, 6.5–11.3) and 15.5 months (95% CI, 12.6–17.1), respectively. According to the Response Assessment in Neuro‐Oncology (RANO) criteria, the disease control rate in the anlotinib group [93.3%, 95% confidence interval (CI), 70.2–98.8] was significantly higher than those without anlotinib (64%, 95% CI: 40.5–79.8, p = 0.039). The median PFS of patients with and without anlotinib was 11.6 months (95% CI, 7.8–14.3) and 6.4 months (95% CI, 4.3–10.3), respectively. Both the median PFS and OS of DMG patients treated with anlotinib were longer than those without anlotinib in the infratentorial patients (PFS: 10.3 vs. 5.4 months, p = 0.006; OS: 16.6 vs. 8.7 months, p = 0.016). Multivariate analysis also indicated anlotinib (HR: 0.243, 95% CI: 0.066–0.896, p = 0.034) was an independent prognosticator for longer OS in the infratentorial subgroup. In addition, the adverse events of anlotinib administration were tolerable in the whole cohort.Conclusions: This study first reported that anlotinib combined with Stupp regimen is a safe and feasible regimen for newly diagnosed patients with H3K27M‐DMG. Further, anlotinib showed significant efficacy for H3K27M‐DMG located in the infratentorial region.