Even though chemotherapy and immunotherapy emerged to limit continual and unregulated proliferation of cancer cells, currently available therapeutic agents are associated with high toxicity levels and low success rates. Additionally, ongoing multi-targeted therapies are limited only for few carcinogenesis pathways, due to continually emerging and evolving mutations of proto-oncogenes and tumor-suppressive genes. CRISPR/Cas9, as a specific gene-editing tool, is used to correct causative mutations with minimal toxicity, but is also employed as an adjuvant to immunotherapy to achieve a more robust immunological response. Some of the most critical limitations of the CRISPR/Cas9 technology include off-target mutations, resulting in nonspecific restrictions of DNA upstream of the Protospacer Adjacent Motifs (PAM), ethical agreements, and the lack of a scientific consensus aiming at risk evaluation. Currently, CRISPR/Cas9 is tested on animal models to enhance genome editing specificity and induce a stronger anti-tumor response. Moreover, ongoing clinical trials use the CRISPR/Cas9 system in immune cells to modify genomes in a target-specific manner. Recently, error-free in vitro systems have been engineered to overcome limitations of this gene-editing system. The aim of the article is to present the knowledge concerning the use of CRISPR Cas9 technique in targeting treatment-resistant cancers. Additionally, the use of CRISPR/Cas9 is aided as an emerging supplementation of immunotherapy, currently used in experimental oncology. Demonstrating further, applications and advances of the CRISPR/Cas9 technique are presented in animal models and human clinical trials. Concluding, an overview of the limitations of the gene-editing tool is proffered.

Department of Anatomy Poznan University of Medical Sciences 60 781 Poznań Poland

Department of Basic and Preclinical Sciences Institute of Veterinary Medicine Nicolaus Copernicus University in Torun 87 100 Toruń Poland

Department of Biomaterials and Experimental Dentistry Poznan University of Medical Sciences 60 812 Poznań Poland

Department of Cancer Diagnostics and Immunology Greater Poland Cancer Centre 61 866 Poznan Poland

Department of Cancer Immunology Poznan University of Medical Sciences 60 408 Poznan Poland

Department of Histology and Embryology Poznan University of Medical Sciences 60 781 Poznań Poland

Department of Obstetrics and Gynecology University Hospital and Masaryk University 601 77 Brno Czech Republic

Department of Periodontology and Oral Implantology Dental Research Division University of Guarulhos Guarulhos 07023 070 Brazil

Department of Toxicology Poznan University of Medical Sciences 61 631 Poznań Poland

Department of Veterinary Surgery Nicolaus Copernicus University in Torun 87 100 Toruń Poland

Physiology Graduate Program North Carolina State University Raleigh NC 27695 USA

Prestage Department of Poultry Science North Carolina State University Raleigh NC 27695 USA

The School of Medicine Medical Sciences and Nutrition University of Aberdeen Aberdeen AB25 2ZD UK

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Targeting Oncogenic Pathways in the Era of Personalized Oncology: A Systemic Analysis Reveals Highly Mutated Signaling Pathways in Cancer Patients and Potential Therapeutic Targets