Evolving skin cancer therapeutics: molecular and genetic drivers, immunotherapy challenges, and advances in nanogel-based nanomedicine

Skin cancer is among the most common malignancies worldwide, with a rising global incidence. Cancer develops through complex molecular and genetic changes. Current treatments, such as surgery, chemotherapy, targeted therapy, radiation, and immunotherapy, offer hope. However, challenges like immune evasion, drug resistance, and systemic toxicities prevent long-term success. Nanotechnology-based delivery systems may offer a potential solution to these challenges. Cross-linked polymeric nanogel networks are unique nanocarriers with high drug-loading capacity, biocompatibility, stimuli-responsive release, and enhanced dermal/transdermal penetration. Preclinical studies have investigated nanogels as delivery platforms for chemotherapeutics, phytochemicals, and immunomodulators, with reported improvements in drug loading, controlled release, dermal penetration, and antitumor activity. However, the available evidence remains predominantly preclinical, and further investigation is needed to determine the clinical efficacy and safety of nanogel-based approaches in skin cancer. This review explains the molecular pathology of skin cancer, the advances and limitations of immunotherapy, and the emerging role of nanogels in cancer treatment. It highlights nanogels as a versatile platform for improving dermal and transdermal drug delivery and as a promising approach for enhancing skin cancer treatment. Further well-designed clinical studies are required to bring nanogel-based delivery system from bench to bed-side.