This manuscript provides an update to the literature on molecules with roles in tumor resistance therapy in head and neck squamous cell carcinoma (HNSCC). Although significant improvements have been made in the treatment for head and neck squamous cell carcinoma, physicians face yet another challenge—that of preserving oral functions, which involves the use of multidisciplinary therapies, such as multiple chemotherapies (CT) and radiotherapy (RT). Designing personalized therapeutic options requires the study of genes involved in drug resistance. This review provides an overview of the molecules that have been linked to resistance to chemotherapy in HNSCC, including the family of ATP-binding cassette transporters (ABCs), nucleotide excision repair/base excision repair (NER/BER) enzymatic complexes (which act on nonspecific DNA lesions generated by gamma and ultraviolet radiation by cross-linking and forming intra/interchain chemical adducts), cisplatin (a chemotherapeutic agent that causes DNA damage and induces apoptosis, which is a paradox because its effectiveness is based on the integrity of the genes involved in apoptotic signaling pathways), and cetuximab, including a discussion of the genes involved in the cell cycle and the proliferation of possible markers that confer resistance to cetuximab.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population with potent immunosuppressive functions. They play major roles in cancer and many of the pathologic conditions associated with inflammation. Long non-coding RNAs (lncRNAs) are untranslated functional RNA molecules. The lncRNAs are involved in the control of a wide variety of cellular processes and are dysregulated in different diseases. They can participate in the modulation of immune function and activity of inflammatory cells, including MDSCs. This mini review focuses on the emerging role of lncRNAs in MDSC activity. We summarize how lncRNAs modulate the generation, recruitment, and immunosuppressive functions of MDSCs and the underlying mechanisms.