Sorafenib-associated hand-foot skin reaction: practical advice on diagnosis, mechanism, prevention, and management

Ai, Leilei; Xu, Ziheng; Yang, Bo; He, Qiaojun; Luo, Peihua

doi:10.1080/17512433.2019.1689122

Cited by 27 publications

(19 citation statements)

References 87 publications

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“…A previous meta-analysis reported that VEGFR TKIs increased the risk of HFS (P < 0.00001) (34). Studies have indicated that HFS might result from inhibition of targeted receptors in healthy tissue by anti-angiogenic agents, revealing potential effectiveness of VEGF/VEGFR blockade (35,36). Thus, we proposed that the presence of HFS might be an indicator of effectiveness of fruquintinib, and further studies with large sample size are expected.…”

mentioning

confidence: 74%

Previous Use of Anti-Vascular Endothelial Growth Factor Receptor Agents Decreases Efficacy of Fruquintinib in Metastatic Colorectal Cancer Refractory to Standard Therapies

et al. 2020

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mentioning

confidence: 74%

Previous Use of Anti-Vascular Endothelial Growth Factor Receptor Agents Decreases Efficacy of Fruquintinib in Metastatic Colorectal Cancer Refractory to Standard Therapies

et al. 2020

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“…These results suggest that Huh7 cells could be considered as an HCC cell line with persistent NRF2 activation, and they were used as one screening cell model in this study. On the other hand, to identify selective NRF2 regulators, we used normal keratinocyte cell line HaCaT cells as the other cell model, because hand–foot skin reaction (HFSR) is the most common adverse effect related to sorafenib treatment, which remains the only approved systemic therapy for advanced HCC [ 17 ]. The result confirmed a much lower NRF2 protein expression in HaCaT cells ( Figure S2A ).…”

Section: Resultsmentioning

confidence: 99%

“…Hand–foot skin reaction (HFSR) is one of the most common adverse effects of sorafenib. However, the mechanism of the cutaneous toxicity remains largely unknown, and optimal treatment or prevention has yet to be developed [ 17 , 27 ]. A main feature of HFSR is hyperkeratosis, which is also frequently observed in patients who suffer from adverse effects induced by tyrosine kinase inhibitors.…”

Section: Resultsmentioning

confidence: 99%

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Identification of Beilschmiedia tsangii Root Extract as a Liver Cancer Cell–Normal Keratinocyte Dual-Selective NRF2 Regulator

et al. 2021

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Transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in regulating the expression of genes participating in cellular defense mechanisms against oxidative or xenobiotic insults. However, there is increasing evidence showing that hyperactivation of NRF2 is associated with chemoresistance in several cancers, including hepatocellular carcinoma (HCC), thus making NRF2 an attractive target for cancer therapy. Another important issue in cancer medication is the adverse effects of these substances on normal cells. Here, we attempted to identify a dual-selective NRF2 regulator that exerts opposite effects on NRF2-hyperactivated HCC cells and normal keratinocytes. An antioxidant response element driven luciferase reporter assay was established in Huh7 and HaCaT cells as high-throughput screening platforms. Screening of 3,000 crude extracts from the Taiwanese Indigenous Plant Extract Library resulted in the identification of Beilschmiedia tsangii (BT) root extract as a dual-selective NRF2 regulator. Multiple compounds were found to contribute to the dual-selective effects of BT extract on NRF2 signaling in two cell lines. BT extract reduced NRF2 protein level and target gene expression levels in Huh7 cells but increased them in HaCaT cells. Furthermore, notable combinatory cytotoxic effects of BT extract and sorafenib on Huh7 cells were observed. On the contrary, sorafenib-induced inflammatory reactions in HaCaT cells were reduced by BT extract. In conclusion, our results suggest that the combination of a selective NRF2 activator and inhibitor could be a practical strategy for fine-tuning NRF2 activity for better cancer treatment and that plant extracts or partially purified fractions could be a promising source for the discovery of dual-selective NRF2 regulators.

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“…In China, research by Ai et al. ( 56 ) recruited 871 cases, the largest HFSR trial so far, to assess the prophylactic effect of urea cream, combined with the best supportive therapy (BCS), on HFSR. Their results show that such a combination therapy significantly delayed the first onset of HFSR.…”

Section: Histology Of Hfsrmentioning

confidence: 99%

Apatinib-Induced Hand–Foot Skin Reaction in Chinese Patients With Liver Cancer

et al. 2021

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Apatinib, an anti-tumor drug selectively targeting VEGFR2 (Vascular Endothelia Growth Factor Recpetor-2), has been proven effective in Chinese patients with liver cancer. Generally, treatment with apatinib achieves 16.1% of the overall objective remission rate (ORR) and 55.83% of the disease control rate (DCR) in Chinese patients with liver cancer. However, the prevalence of apatinib-induced hand–foot skin reaction (AI-HFSR) is noticeably high. The incidence of AI-HFSR is about 50.5%, of which Grades 1/2 and 3 are 38.8 and 11.6%, respectively. In addition, potential molecular mechanisms underlying the development of AI-HFSR are poorly understood and urgently needed to be investigated histologically. In this review, we summarize and review the current efficacy of apatinib and the prevalence of AI-HFSR in Chinese patients with liver cancer. Besides, we postulate the potential mechanisms underlying the development of AI-HFSR and discuss the optimal clinical management for this unwanted cutaneous side effect.

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Sorafenib-associated hand-foot skin reaction: practical advice on diagnosis, mechanism, prevention, and management

Cited by 27 publications

References 87 publications

Previous Use of Anti-Vascular Endothelial Growth Factor Receptor Agents Decreases Efficacy of Fruquintinib in Metastatic Colorectal Cancer Refractory to Standard Therapies

Previous Use of Anti-Vascular Endothelial Growth Factor Receptor Agents Decreases Efficacy of Fruquintinib in Metastatic Colorectal Cancer Refractory to Standard Therapies

Identification of Beilschmiedia tsangii Root Extract as a Liver Cancer Cell–Normal Keratinocyte Dual-Selective NRF2 Regulator

Apatinib-Induced Hand–Foot Skin Reaction in Chinese Patients With Liver Cancer

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