Advances in targeted therapy mainly based on signal pathways for nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein–Barr virus. Based on epidemiological data, both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region, in particular, with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy (IMRT) which profoundly contributes to the cure rate of NPC patients. To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment, we discussed the implication of using targeted therapy against critical molecules in various signal pathways, and how they synergize with chemoradiotherapy in the NPC treatment. Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options, which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.

The Stromal and Immune Landscape of Nasopharyngeal Carcinoma and Its Implications for Precision Medicine Targeting the Tumor Microenvironment

“…The function of ECM is primarily involved with the activation of focal adhesion-related pathways, including FAK/SRC, PI3K/AKT and RhoA/ROCK signaling. The predominant ECM components in the NPC microenvironment are collagen (especially type I collagen), lumican, and fibronectin, which all have a positive impact on angiogenesis and anti-apoptosis (50,118,119). Other collagens are also synthesized by intratumoral fibroblasts, such as type III and type IV collagens, but they exhibit patient-specific distribution.…”

Combination of Epithelial Growth Factor Receptor Blockers and CDK4/6 Inhibitor for Nasopharyngeal Carcinoma Treatment

“…Genomic, transcriptomic, bioinformatic, and omics studies have indicated that aberrant signal transduction pathways including epithelial growth factor (EGF) receptor (EGFR), nuclear factor kappa-B (NF-κB) [11], WNT/β-catenin [12], PI3K/Akt/mTOR, p53, PARP, MAPK, STAT, cell cycle pathways, and miRNAs/lncRNAs [13,14] may result in tumor progression and treatment resistance in NPC. EGFR is a tyrosine kinase receptor.…”

miRNAs Associated with Nasopharyngeal Carcinoma: New Prognostic Biomarkers and Therapeutic Targets

“…Although radiotherapy remains the most essential treatment for NPC, the recurrence rate of the disease is as high as 82% due to radiotherapy resistance 3,4 . In recent years, there has been abundant research on radioresistance, drug resistance, and angiogenesis to uncover the underlying mechanisms for miRNA involvement in NPC progression 5 . Changes in radiotherapy sensitivity and the prognosis of NPC patients can also occur due to changes in miRNA expression.…”

“…By in uencing signal pathways, MiRNAs can participate in radiotherapy resistance in NPC cells. For example, NPC cell proliferation and tumor progression are regulated by miR-375, which is up-regulated through the promotion of the pyruvate dehydrogenase kinase 1 (PDK1) / phosphatidylinositol (3,4,5)-trisphosphate (PIP3) / protein kinase B (Akt) axis 6 . In contrast, the down-regulation of miR-429 functions as a tumor suppressor 7 .…”