SiRNA-based Therapeutics in Hormone-driven Cancers: Advancements and Benefits over Conventional Treatments

Hormone-related cancers, also known as hormone-sensitive or hormone-dependent cancers, rely on hormones such as estrogen, testosterone, and progesterone for growth. These malignancies, including breast, pituitary, thyroid, ovarian, uterine, cervical, and prostate cancers, often exhibit accelerated progression in response to hormonal signaling. Small interfering RNA (siRNA) has emerged as a groundbreaking gene suppression therapy since the FDA approval of its first product in 2018. With over 200 ongoing clinical trials, siRNA is being actively explored as a targeted treatment for hormone-related cancers. Its ability to silence specific oncogenes offers significant advantages over conventional therapies, which are often associated with toxicity, resistance, and non-specific targeting. However, challenges in siRNA delivery remain a major barrier to its clinical translation, limiting its ability to reach target cells effectively. This review evaluates the potential of siRNA in hormone-related cancers, addressing the shortcomings of traditional treatments while examining novel strategies to enhance siRNA delivery and overcome tumor microenvironment obstacles. Notably, no existing literature comprehensively consolidates siRNA-based therapies for these cancers, emphasizing the importance of this manuscript in bridging current knowledge gaps and advancing the translational application of siRNA therapeutics.