The inspiration of CRISPR-Cas: Interface of nature with a pharmacy: A compatible horizon of cancer treatment

Abstract

Cancer has always been a complicated disease to understand and treat since it has complex genetic factors, heterogeneity of tumors, resistance to treatment, and metastasis. The traditional treatments of chemotherapies are associated with systemic side effects, whereas targeted therapies and conventional immunotherapies have resistance modalities, immunological evasion, and an inability to address immunologically cold tumors. The urgent need is for the development of long-lasting, low-toxicity therapies that can dynamically overcome resistance and modulate the tumor microenvironment. CRISPR-Cas genome editing, based on bacterial adaptive immunity, represents a paradigm shift in oncology, offering increased accuracy and programmability. This technology enables the direct correction of oncogenes, enhances immune effector cells through multiplex gene editing, and identifies weak spots through functional genomic screens, such as base and prime editing with minimal off-target effects. It also enables the design of universal, off-the-shelf cell therapies and the rational combination of therapies to enhance treatment durability. Nevertheless, there are still some downsides, including delivery efficiency, off-target effects, immunogenicity, and ethical concerns associated with CRISPR-based germline editing. Developments in non-viral delivery systems, high-fidelity Cas variants, AI-based guide RNA design, and natural product-based approaches are helping overcome these limitations. With the right combination of immunotherapy, natural product pharmacology, and predictive machine learning models, CRISPR-Cas systems have the potential to transform cancer, which is often incurable, into a treatable and manageable disease.