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Highlighting the Role of DCLK1 in Tumor Invasion and Potential for Therapeutic Intervention
Molly E Muehlebach1, Sufi Mary Thomas1
1Department of Otolaryngology - Head and Neck Surgery, University of Kansas Medical Center, Kansas City, KS, USA.
Abstract:
Head and neck squamous cell carcinoma (HNSCC) accounts for nearly 5% of global cancer deaths per year, with epidemiological studies suggesting an expected 30% increase in cases by 2030 due to rising incidence of viral infection (i.e. huma papilloma virus [HPV]). Treatment consists primarily of surgical tumor removal accompanied by post-operative chemoradiation therapy; however, disease recurrence is still an issue amongst 10-26% of patients. Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated protein with dual kinase activity, and upregulation has been associated with poor prognosis in multiple solid tumors. Recent studies by Arnold et al. highlighted a definitive role of DCLK1 in HNSCC invadopodium formation and function, and has elucidated its potential for small molecule targeting. This commentary summarizes the molecular findings by Arnold et al. and evaluates them in regard to the current standings of DCLK1 targeting, emphasizing why inhibiting this molecule could be of clinical significance.
Insights
Head and neck squamous cell carcinoma (HNSCC) involves increasing viral infections. Targeting Doublecortin-like kinase 1 (DCLK1) shows promise for improving treatment outcomes in HNSCC patients.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Head and neck squamous cell carcinoma (HNSCC) represents a significant global health burden, with projected increases due to rising human papillomavirus (HPV) infections.
- Current treatments, including surgery and chemoradiation, have limitations, as 10-26% of patients experience disease recurrence.
- Doublecortin-like kinase 1 (DCLK1), a protein kinase, is upregulated in various cancers and linked to poor prognosis.
Purpose of the Study:
- To summarize and evaluate recent findings on the role of DCLK1 in HNSCC.
- To assess the potential of targeting DCLK1 as a therapeutic strategy for HNSCC.
Main Methods:
- Review and commentary on molecular findings regarding DCLK1's function in HNSCC.
- Evaluation of DCLK1's role in invadopodium formation and function.
- Assessment of current DCLK1 targeting strategies.
Main Results:
- Recent studies demonstrate a critical role for DCLK1 in HNSCC invadopodium formation and function.
- DCLK1 has been identified as a potential target for small molecule inhibitors.
- Upregulation of DCLK1 correlates with poor prognosis in HNSCC.
Conclusions:
- Inhibiting DCLK1 may represent a clinically significant therapeutic approach for HNSCC.
- Targeting DCLK1 offers a promising avenue for overcoming treatment resistance and improving patient outcomes in HNSCC.
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