Researchers Identify Multidrug Chemotherapy Resistant Genes

On September 4, 2023, a study published in Molecular Cancer identified gene variations that led to multidrug chemoresistance in head and neck squamous cell carcinoma (HNSCC) cells. This discovery is vital as multidrug resistance is the primary reason for treatment failure in HNSCC.

According to the study, roughly 90% of all head and neck cancers are HNSCC, with alcohol and tobacco use being associated with most cases. Generally, HNSCC is treated with a combination of chemotherapy drugs or radiotherapy.

The most common chemotherapy drugs involved in multimodal therapy are cisplatin, 5-fluorouracil (5FU), paclitaxel (PTX), and docetaxel (DTX). With these tools, the condition has a 70–90% five-year survival rate if caught in its early stages.

Despite the availability of various treatment options, the overall survival rate of the condition hovers around 50%. Researchers explained that most patients, approximately two-thirds, are not diagnosed until they are in the advanced stages of disease. At that point, limitations in treatment options and treatment failures contribute to reduced survival rates.

“Unlike lung and breast cancer patients, all HNSCC patients are treated with almost the same combinations of treatment irrespective of the genetic makeup of their cancer. This is mainly due to a poor understanding of the molecular heterogeneity of HNSCC. Research into molecular biomarkers that can stratify sub-populations and indicate the most suitable intervention based on individual patient’s tumor molecular profile would reduce toxicity, improve morbidity and treatment outcome,” explained researchers in the study.

Researchers have explored multiple factors that may contribute to chemoresistance in patients with HNSCC, including cell death pathways, DNA damage repair, epithelial-mesenchymal transition, miRNA processing, and immune cell interactions.

Researchers analyzed chemoresistant cell line models using bioinformatic transcriptome data mining and differential gene expression. Researchers identified ten multidrug chemoresistance genes: TOP2A DNMT1, INHBA, CXCL8, NEK2, FOXO6, VIM, FOXM1B, NR3C1, and BIRC5.

“This finding may lead to novel personalized biomarker-linked therapeutics that can prevent and/or abrogate chemoresistance in HNSCC and other tumor types with elevated NEK2 and INHBA expression. Further investigation is necessary to delineate their signaling mechanisms in tumor chemoresistance,” concluded the researchers in the publication.