Managing cancer in autoimmune patients: Overcoming therapeutic challenges and expanding treatment options

The intricate interplay between cancer and autoimmune diseases (ADs) is rooted in immune dysregulation, where genetic susceptibility, chronic inflammation, epigenetic modifications, and immunosuppressive therapies contribute to tumorigenesis. The dualistic nature of immune activation complicates therapeutic strategies, as immune checkpoint inhibitors and other immune-stimulatory therapies may exacerbate underlying ADs, leading to immune-related adverse events (irAEs), including organ toxicity, dermatologic reactions, and disease flares. Conversely, immunosuppressive treatments aimed at controlling ADs can compromise anti-tumor immunity and reduce the efficacy of cancer therapies. This necessitates a precision-medicine approach that balances effective tumor control with mitigation of immune-mediated complications. This review explores current therapeutic challenges and opportunities in managing cancer patients with pre-existing autoimmune conditions. Emphasis is placed on alternative treatment modalities, including targeted therapies such as kinase inhibitors (e.g., sorafenib), and adoptive cellular therapies like CAR-T and CAR-NK cells, which exhibit selective tumor targeting with a potentially reduced risk of irAEs. Moreover, natural compounds with dual immunomodulatory and antitumor properties offer a promising therapeutic avenue due to their multi-targeting capabilities and favorable safety profiles. Through case-based analysis, we highlight strategies that simultaneously address tumor progression and autoimmune dysregulation, underscoring the need for integrated, individualized therapeutic regimens in this complex patient population.