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Updated: Jan 12, 2026
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Metabolic cell deaths in head and neck cancer: mechanisms, therapeutic potential, and challenges
1Department of Otorhinolaryngology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Background:
Head and neck cancer (HNC) poses prominent clinical challenges: limited early diagnosis efficacy, suboptimal five-year survival after conventional treatment, over 60% of patients at advanced/metastatic stages, and lymph node metastasis accelerating progression. Metabolic cell death (ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, alkaliptosis) offers promising HNC therapeutic avenues, while their crosstalk, synergy with standard therapies and translation hurdles require attention.
Main Findings:
Ferroptosis inducers demonstrate capacity to reverse HNC drug resistance and synergize with chemoradiotherapy, yet elevated FSP1 expression drives resistance. Cuproptosis inducers combined with immunotherapy reprogram the tumor microenvironment, with HIF-1α mediating resistance to this combination. HNC exhibits sensitivity to disulfidptosis, but its in vivo/in vitro validation in HNC remains insufficient. Lysozincrosis, triggered by lysosomal zinc release, has TRPML1 as a potential target due to HNC's active lysosomal function. Alkaliptosis induces selective cancer cell death and is regulated by CA9 and NF-κB. These pathways interact, and their translation is hindered by tumor heterogeneity and poor delivery efficiency.
Future Directions:
Future studies should prioritize clarifying these pathways' regulatory network, address translation hurdles, develop multi-target strategies and tumor-targeted delivery systems, and enhance therapy synergy to improve HNC prognosis.
Insights
Metabolic cell death pathways like ferroptosis offer new head and neck cancer (HNC) treatments. Further research is needed to overcome resistance and delivery challenges for improved patient outcomes.
Area of Science:
- Oncology
- Cellular Biology
- Cancer Therapeutics
Background:
- Head and neck cancer (HNC) presents significant clinical challenges, including late diagnosis and poor survival rates.
- Metabolic cell death mechanisms (ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, alkaliptosis) are emerging as potential therapeutic strategies for HNC.
- Understanding the interplay and translational challenges of these pathways is crucial for advancing HNC treatment.
Purpose of the Study:
- To explore the potential of various metabolic cell death pathways in treating head and neck cancer.
- To review the current findings on ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, and alkaliptosis in the context of HNC.
- To identify challenges and future directions for translating these novel therapeutic avenues into clinical practice.
Main Methods:
- Review of existing literature on metabolic cell death pathways in head and neck cancer.
- Analysis of mechanisms of action, resistance, and synergy with conventional therapies.
- Identification of key molecular targets and regulatory networks.
Main Results:
- Ferroptosis inducers can overcome drug resistance and synergize with chemoradiotherapy, though FSP1 confers resistance.
- Cuproptosis combined with immunotherapy can modulate the tumor microenvironment, with HIF-1α involvement in resistance.
- HNC shows sensitivity to disulfidptosis, but requires further in vivo/in vitro validation. Lysozincrosis targets TRPML1, and alkaliptosis involves CA9 and NF-κB.
- Tumor heterogeneity and delivery efficiency are significant hurdles for clinical translation.
Conclusions:
- Metabolic cell death pathways hold significant promise for head and neck cancer therapy.
- Overcoming resistance mechanisms and improving drug delivery are critical for clinical success.
- Future research should focus on elucidating regulatory networks, developing targeted delivery systems, and enhancing therapeutic synergy to improve HNC prognosis.
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