Genome Editing Approaches with CRISPR/Cas9 for Cancer Treatment: Critical Appraisal of Preclinical and Clinical Utility, Challenges, and Future Research

The increasing burden on human malignant diseases became a major concern for healthcare practitioners, that must deal with tumor relapse and the inability to efficiently treat metastasis, in addition to side effects. Throughout the decades, many therapeutic strategies have been employed to improve the clinical outcomes of cancer patients and great efforts have been made to develop more efficient and targeted medicines. The malignant cell is characterized by genetic and epigenetic modifications, therefore targeting those specific drivers of carcinogenesis is highly desirable. Among the genome editing technologies, CRISPR/Cas9 stood as a promising candidate for cancer treatment alternatives, due to its low complexity design. First described as a defense mechanism of bacteria against invading foreign DNA, later it was shown that CRISPR components can be engineered to target specific DNA sequences in a test tube, a discovery that was awarded later with the Nobel Prize in chemistry for its rapid expansion as a reliable genome editing tool in many fields of research, including medicine. The present paper aims of describing CRISPR/Cas9 potential targets for malignant disorders, and the approaches used for achieving this goal. Aside from preclinical studies, we also present the clinical trials that use CRISPR-based technology for therapeutic purposes of cancer. Finally, a summary of the presented studies adds a more focused view of the therapeutic value CRISPR/Cas9 holds and the associated shortcomings

Melanoma Cellular Signaling Transduction Pathways Targeted by Polyphenols Action Mechanisms

Melanoma is the most aggressive type of skin cancer. Although different anti-melanoma treatments are available, their efficacy is still improvable, and the number of deaths continues to increase worldwide. A promising source of antitumor agents could be presented by polyphenols—natural plant-based compounds. Over the past decades, many studies have described multiple anticancer effects of polyphenols in melanoma, presenting their potential interactions with targeted molecules from different signaling pathways. However, to our knowledge, there is no comprehensive review on polyphenols-regulated mechanisms in melanoma cells available in the literature. To fulfill this gap, this article aims to summarize the current knowledge of molecular mechanisms of action regulated by polyphenols involved in melanoma initiation and progression. Here, we focus on in vitro and in vivo effects of polyphenol treatments on tumor-essential cellular pathways, such as cell proliferation, apoptosis, autophagy, inflammation, angiogenesis, and metastasis. Moreover, emerging studies regarding the well-marked role of polyphenols in the regulation of microRNAs (miRNAs), highlighting their contribution to melanoma development, are also epitomized. Finally, we hope this review will provide a firm basis for developing polyphenol-based therapeutic agents in melanoma treatment