Head and neck cancers remain challenging to treat due to high recurrence rates and limited response to conventional therapies, such as chemo and radiotherapy. RNA-based therapeutics offer a promising avenue for addressing these challenges by targeting molecular drivers of tumour growth and therapy resistance. MicroRNA-7 (miR-7) has emerged as a promising anti-cancer microRNA, regulating key oncogenic pathways such as EGFR/PI3K/AKT signalling.
In this study, we evaluated miR-7-based therapy in combination with standard-of-care treatments using preclinical models of head and neck cancer. We employed cell cultures, patient-derived organoids, and cell line–derived xenografts in mice to assess the impact of a miR-7 mimic on tumour growth, survival, migration, invasion, and response to cisplatin and radiotherapy. Comprehensive RNA and protein profiling was performed to elucidate the mechanisms of exogenous miR-7.
Our findings show that miR-7-based therapy suppresses tumour growth and motility across multiple models, while inducing cell cycle arrest, apoptosis, and senescence through modulation of oxidative stress and autophagic flux. Moreover, miR-7 therapy acted synergistically with cisplatin and radiotherapy, highlighting its potential to enhance current treatment strategies. A chemically modified miR-7 mimic with improved stability and potency, currently under development, represents a promising candidate for future clinical translation.