Electrochemotherapy: An Alternative Strategy for Improving Therapy in Drug-Resistant SOLID Tumors

SIMPLE SUMMARY: Chemotherapy is becoming an increasingly difficult antitumor therapy to practice due to the multiple mechanisms of drug resistance. To overcome the problem, it is possible to use alternative techniques, such as electrochemotherapy, which involves the simultaneous administration of the electrical pulse (electroporation) and the treatment with the drug in order to improve the effectiveness of the drug against the tumor. Electroporation has improved the efficacy of some chemotherapeutic agents, such bleomycin, cisplatin, mitomycin C, and 5-fluorouracil. The results of in vitro, veterinary, and clinical oncology studies are promising on various cancers, such as metastatic melanoma. The purpose of this review is to give an update on the state of the art of electrochemotherapy against the main solid tumors in the preclinical, clinical, and veterinary field. ABSTRACT: Electrochemotherapy (ECT) is one of the innovative strategies to overcome the multi drug resistance (MDR) that often occurs in cancer. Resistance to anticancer drugs results from a variety of factors, such as genetic or epigenetic changes, an up-regulated outflow of drugs, and various cellular and molecular mechanisms. This technology combines the administration of chemotherapy with the application of electrical pulses, with waveforms capable of increasing drug uptake in a non-toxic and well tolerated mechanical system. ECT is used as a first-line adjuvant therapy in veterinary oncology, where it improves the efficacy of many chemotherapeutic agents by increasing their uptake into cancer cells. The chemotherapeutic agents that have been enhanced by this technique are bleomycin, cisplatin, mitomycin C, and 5-fluorouracil. After their use, a better localized control of the neoplasm has been observed. In humans, the use of ECT was initially limited to local palliative therapy for cutaneous metastases of melanoma, but phase I/II studies are currently ongoing for several histotypes of cancer, with promising results. In this review, we described the preclinical and clinical use of ECT on drug-resistant solid tumors, such as head and neck squamous cell carcinoma, breast cancer, gynecological cancer and, finally, colorectal cancer.