1. Standard Clinical Treatment Modalities
First-Line Surgical Options: Surgical excision serves as the primary frontline intervention for larger cutaneous squamous cell carcinoma (SCC) lesions.
Alternative & Low-Risk Modalities: For smaller or low-risk lesions, electrodesiccation and curettage are routinely utilized alongside photodynamic therapy and cryosurgery.
Adjuvant & Systemic Therapies: Additional clinical approaches include topical medications, radiotherapy, and systemic chemotherapies. However, demand remains for novel therapeutics that combine high efficacy with low side effects.
2. Drug Repurposing: Albendazole in Cutaneous SCC
Selective Cytotoxicity: The FDA-approved anthelmintic agent albendazole significantly reduces the cell viability of human cutaneous SCC cell lines (SCC12 and SCC13) at concentrations above 0.2 µM.
Cancer-Specific Apoptosis: Albendazole induces dose-dependent apoptosis in SCC cells, evidenced by elevated TUNEL-positive staining and dose-dependent cleavage of PARP-1 and caspase-3. Notably, it exhibits high selectivity for malignant cells, failing to induce PARP-1 or caspase-3 cleavage in normal human epidermal keratinocytes even at 1.0 µM.
3. Molecular Mechanisms: ER Stress & Stemness Blockade
Endoplasmic Reticulum (ER) Stress Induction: Albendazole triggers severe ER stress in SCC cells, marked by time-dependent increases in CHOP, ATF-4, caspase-4, and caspase-12. Pretreatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) significantly attenuates albendazole-induced cell death.
Inhibition of Cancer Stemness: At sub-lethal, non-toxic concentrations (0.05 µM and 0.1 µM), albendazole markedly suppresses the colony-forming ability of SCC cells.
Wnt/β-Catenin Pathway Blockade: This suppression of cancer stemness is driven by downregulating the canonical Wnt/β-catenin pathway, as evidenced by reduced TOPflash reporter luciferase activity and decreased β-catenin protein levels.
Antitumor Effect of Albendazole on Cutaneous Squamous Cell Carcinoma (SCC) Cells
Zhang, Qing-Ling, Lian, De-De, Zhu, Ming Ji, Li, Xue Mei, Lee, Jae Kyung, Yoon, Tae-Jin, Lee, Jeung-Hoon, Jiang, Ri-Hua, Kim, Chang Deok, Antitumor Effect of Albendazole on Cutaneous Squamous Cell Carcinoma (SCC) Cells, BioMed Research International, 2019, 3689517, 9 pages, 2019. https://doi.org/10.1155/2019/3689517
https://onlinelibrary.wiley.com/doi/epdf/10.1155/2019/3689517