RNA cargo in motion: The exosomal connection to head and neck cancers

Researchers from SRM Institute of Science and Technology, led by Dr. KN Aruljothi, have published a study in ExRNA highlighting the role of exosomal RNA (exRNA) in head and neck cancers (HNCs). Exosomal RNAs, including miRNA, mRNA, and lncRNA, are secreted by tumor cells and play a pivotal role in cancer progression by modulating key signaling pathways such as NF-κB, EGFR, and PI3K/AKT/mTOR. These exRNAs influence the tumor microenvironment, promote metastasis, and contribute to immune evasion and therapy resistance. The study underscores the potential of exRNA-based liquid biopsy through saliva and blood samples for early diagnosis and treatment monitoring, presenting a promising avenue for precision oncology in HNC management.

Head and neck cancers (HNCs) are a group of malignancies affecting the oral cavity, pharynx, larynx, nasal cavity, and salivary glands, with head and neck squamous cell carcinoma (HNSCC) being the most common subtype. Risk factors include tobacco and alcohol use, human papillomavirus (HPV) infection, and environmental carcinogens such as wood dust and formaldehyde. While conventional diagnostic methods rely on invasive tissue biopsies, exosomal RNA (exRNA) has emerged as a promising non-invasive biomarker for the early detection and monitoring of HNCs.

Exosomes are extracellular vesicles (EVs) derived from multivesicular bodies (MVBs) that transport various molecular components, including miRNAs, mRNAs, and long non-coding RNAs (lncRNAs). These exRNAs play a crucial role in cancer biology by modulating gene expression, facilitating immune evasion, and altering the tumor microenvironment. By regulating essential signaling pathways, exRNAs contribute to tumor proliferation, metastasis, and chemoresistance, making them valuable targets for cancer diagnosis and therapy.

Different classes of exosomal RNAs serve distinct functions in HNC progression. MicroRNAs such as miR-21, miR-486, and miR-10b promote tumor cell proliferation, immune escape, and drug resistance. Long non-coding RNAs, including HOTAIR and MALAT1, enhance cancer cell invasion and motility, while exosomal mRNAs, such as EGFR and TP53, regulate key oncogenic pathways. Additionally, circular RNAs (circRNAs) and PIWI-interacting RNAs (piRNAs) aid cancer cells in evading immune surveillance and adapting to therapeutic stress.

ExRNAs critically modulate major cancer-associated pathways, including the NF-κB pathway, which sustains tumor inflammation and survival, and the EGFR and PI3K/AKT/mTOR pathways, which regulate cellular proliferation, metabolic adaptation, and treatment resistance. Furthermore, the TP53 pathway, a crucial tumor suppressor mechanism, is influenced by exRNA activity, either promoting or inhibiting tumor progression. The Cyclin-CDK pathway, essential for cell cycle regulation, is also impacted by exosomal RNAs, contributing to uncontrolled cancer cell growth.

The clinical potential of exRNAs in liquid biopsy is particularly significant, as their detection in saliva and blood enables non-invasive, real-time cancer diagnostics. Beyond their diagnostic applications, exRNA-based therapeutic strategies hold promise, including the inhibition of exosomal RNA-mediated tumor progression and the utilization of engineered exosomes for targeted RNA delivery.

Despite these advancements, challenges remain in standardizing exosome isolation techniques, identifying specific RNA biomarkers, and developing targeted therapies. Future research should focus on optimizing exRNA-based therapeutic delivery systems, elucidating the mechanisms underlying exRNA-mediated cancer progression, and validating their clinical utility in precision oncology.

In conclusion, exosomal RNAs represent a transformative tool for advancing head and neck cancer diagnosis and treatment. Their dual role as biomarkers and therapeutic targets underscores their potential to revolutionize cancer management. The integration of exRNA-based approaches with conventional therapies can significantly enhance precision medicine strategies, offering improved clinical outcomes for HNC patients.
Thasma Loganathan VK, Satishkartik S, Pattabiram S, Suresh Kumar A, Chattopadhyay S, et al. RNA cargo in motion: the exosomal connection to head and neck cancers. ExRNA 2025(1):0003, https://doi.org/10.55092/exrna20250003.