Methods for Overcoming Chemoresistance in Head and Neck Squamous Cell Carcinoma: Keeping the Focus on Cancer Stem Cells, a Systematic Review
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Natural Products
Mechanism of Action on CSCs | Effect on Conventional Chemotherapy | |
---|---|---|
Ganoderma lucidum (GL) [52,53] | Fungal immunomodulatory proteins block IL-6/Stat3 signaling. | Decreased resistance to CDDP. |
Sulforaphane (SF) [55,56] | Stimulation of caspase-dependent apoptotic pathway, inhibition of Sonic Hedgehog (SHH) pathway and decreased expression of SOX2 and OCT4. | Enhances the effectiveness of CDDP and 5-fluorouracil (5-FU) chemotherapy. |
Honokiol [61,62,63,64] | Lowers CD44 expression and ALDH1 activity in CSCs; Suppresses the phosphorylation of STAT3, possibly through the decrease of IL-6, a growth factor that stimulates STAT3. | Increases effects of CDDP, and it has an additive effect on 5-fluorouracil. |
Phenanthrene alkaloid Berberine [69] | Reduces miR-21 expression in a dose-dependent manner; decreases CSCs marker expression. | Increases effects of CDDP. |
Isoliquiritigenin (ISL) [73,74] | Downregulates GRP78 and decreases CSCs marker expression; Decreases ABCG2 expression. | Increases effects of CDDP. |
Quercetin (Qu) [75] | Downregulates HSP27; Disrupts the p38 MAPK-Hsp27 axis. | Increases effects of CDDP. |
Ovatodiolide (Ova) [78] | Dysregulates the JAK2/STAT3 signaling pathway. | Increases effects of CDDP. |
Celastrol [79] | Spindle Pole body Component 25 (SPC25) inhibitor. | Increases effects of CDDP. |
Curcumin [80] | Decreases the expression of stemness markers and reverses the CD44 + and side population (SP) cell ratios by inhibiting RXRα. | Increases effects of CDDP. |
Magnoliol [84,85,86] | Suppresses mitochondrial respiration at complex I of the electron transport chain; inhibits the IL-6/Stat3 pathway. | Increases effects of CDDP. |
Melatonin (N-acetyl-5-methoxytryptamine) [88,89] | Upregulates miR-181c-5p expression, which decreases DERL-1 expression. | Enhances cisplatin-induced cell death in mesenchymal-like CD44high cells. |
3.2. Adjuvant Molecules to Traditional Chemotherapy
Mechanism of Action on CSCs | Effect on Conventional Chemotherapy | |
---|---|---|
ML-385 [91] | Inhibitor of NRF2; reduces CD44 expression | Increases effects of CDDP. |
Chloroquine (CQ) [91] | Reduces CD44 expression | Increases effects of CDDP. |
Tubastatin A [92,93,94] | Pharmaceutical inhibitor of HDAC6 | Increases effects of CDDP. |
Fenofibrate [95] | Reduces the expression of NF-κB p50 and p65 subunits. | Potential for increased effects of CDDP. |
Dehydroepiandrosterone (DHEA) [96,97,98] | Inhibits the WNT pathway in vitro and lowers tumorigenicity in vivo | Unknown |
XAV939 [99,100] | Downregulates the expression of β-catenin | Unknown |
Suberoylanilide hydroxamic acid (SAHA) [101,102,103] | Pan-HDAC inhibitor; reduces nanog expression in HPV-positive and -negative HNSCC | Increases effects of CDDP. |
sFRP4 [104] | WNT antagonist | Unknown |
Curcumin-difluorinated (CDF) [105,106,107,108] | Synthetic analog of curcumin. | Unknown |
Valproic Acid (VPA) [109,110,111,112] | Inhibits HDACs | Increases effects of CDDP. |
Tocilizumab [113] | Humanized anti-IL-6R monoclonal antibody; inhibits Bmi-1 function. | Increases effects of CDDP. |
temsirolimus, BKM120, AZD8055, PF4708671 [114,115] | PI3k/mTOR signaling inhibitors; decreases Bmi-1 expression. | Increases effects of CDDP. |
Anti-PD-1 [115] | Decreases Bmi-1 expression | Increases effects of CDDP. |
3.3. CSCs Targeting from Patient’s Fresh Biopsies for Functional Precision Therapy
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
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Bizzoca, M.E.; Caponio, V.C.A.; Lo Muzio, L.; Claudio, P.P.; Cortese, A. Methods for Overcoming Chemoresistance in Head and Neck Squamous Cell Carcinoma: Keeping the Focus on Cancer Stem Cells, a Systematic Review. Cancers 2024, 16, 3004. https://doi.org/10.3390/cancers16173004
Bizzoca ME, Caponio VCA, Lo Muzio L, Claudio PP, Cortese A. Methods for Overcoming Chemoresistance in Head and Neck Squamous Cell Carcinoma: Keeping the Focus on Cancer Stem Cells, a Systematic Review. Cancers. 2024; 16(17):3004. https://doi.org/10.3390/cancers16173004
Chicago/Turabian StyleBizzoca, Maria Eleonora, Vito Carlo Alberto Caponio, Lorenzo Lo Muzio, Pier Paolo Claudio, and Antonio Cortese. 2024. "Methods for Overcoming Chemoresistance in Head and Neck Squamous Cell Carcinoma: Keeping the Focus on Cancer Stem Cells, a Systematic Review" Cancers 16, no. 17: 3004. https://doi.org/10.3390/cancers16173004