Abstract
The purpose of this review was to summarise available literature concerning the anticancer effects of both putative and validated BH3-mimetics in head and neck squamous cell carcinomas. A literature search was performed and studies assessing malignant cell lines, xenograft models, and/or humans were considered eligible. A total of 501 studies were identified, of which 40 were included. One phase-II clinical trial assessing gossypol (combined with docetaxel) was found. The remaining 39 preclinical studies investigated cell lines and/or xenograft models involving the use of six validated BH3-mimetics (A-1210477, A-1331852, ABT-737, navitoclax, S63845, venetoclax) and six putative BH3-mimetics (ApoG2, gossypol, obatoclax, sabutoclax, TW-37, and YC137). In preclinical settings, most validated BH3-mimetics were capable of inducing apoptosis (in-vitro) and tumour growth inhibition (in-vivo). The majority of putative BH3-mimetics were also capable of inducing cell death, although important off-target effects, such as autophagy induction, were also described. Combinations with conventional anticancer drugs, ionising radiation, or multiple BH3-mimetics generally resulted in enhanced anticancer effects, such as increased sensitivity to apoptotic stimuli, especially considering some cell lines that showed resistance to either treatment alone. In conclusion, although clinical data are still insufficient to evaluate the anticancer effects of BH3-mimetics in head and neck squamous cell carcinomas, promising results in preclinical settings were observed concerning induction of cell death and inhibition of tumour growth. Therefore, further clinical trials are highly encouraged.
Original language | English |
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Article number | 105979 |
Number of pages | 20 |
Journal | Oral Oncology |
Volume | 132 |
Early online date | 8 Jul 2022 |
DOIs | |
Publication status | Published - Sept 2022 |
Bibliographical note
Funding Information:GM (grant number 88887.200723/2018-00) is supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, number 427464/2018-8).
Publisher Copyright:
© 2022 Elsevier Ltd
Keywords
- Head and Neck Neoplasms
- Head and Neck Cancer
- Drug Therapy
- Apoptosis
- Bcl-2 family
- BH3
- Targeted Therapy
- BCL-2
- BCL-XL
- BCL-W
- MCL-1