EGFR/ERBB2 Amplifications and Alterations Associated With Resistance to Lenvatinib in Hepatocellular Carcinoma

Lim, Mir; Franses, Joseph W.; Imperial, Robin John Lester; Majeed, Umair; Tsai, Jill; Hsiehchen, David

doi:10.1053/j.gastro.2023.01.023

Cited by 12 publications

(3 citation statements)

References 10 publications

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“…Few studies have shown an activation of the EGFR as a potential mechanism of lenvatinib resistance [169,170]. In clinical settings, EGFR amplifications detected by circulating tumor DNA (ctDNA) were observed in patients who started to progress while treated with lenvatinib [171]. The use of lenvatinib with an EGFR inhibitor could reverse the resistance in vitro [169].…”

Section: Lenvatinibmentioning

confidence: 99%

New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma—Today and Tomorrow

Becht,

Kiełbowski,

Wasilewicz

2024

IJMS

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Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Liver cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease represent major risk factors of HCC. Multiple different treatment options are available, depending on the Barcelona Clinic Liver Cancer (BCLC) algorithm. Systemic treatment is reserved for certain patients in stages B and C, who will not benefit from regional treatment methods. In the last fifteen years, the arsenal of available therapeutics has largely expanded, which improved treatment outcomes. Nevertheless, not all patients respond to these agents and novel combinations and drugs are needed. In this review, we aim to summarize the pathway of trials investigating the safety and efficacy of targeted therapeutics and immunotherapies since the introduction of sorafenib. Furthermore, we discuss the current evidence regarding resistance mechanisms and potential novel targets in the treatment of advanced HCC.

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Section: Lenvatinibmentioning

confidence: 99%

New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma—Today and Tomorrow

Becht,

Kiełbowski,

Wasilewicz

2024

IJMS

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“…For instance, Lim et al. analysed genetic alterations of EGFR pathway in 46 patients with HCC, they found that patients treated with lenvatinib have an increasing trend in the number of EGFR and ERBB2 gene mutations, indicating that this change is a response to lenvatinib 26 . He et al.…”

Section: Possible Mechanisms Of Resistance To Lenvatinibmentioning

confidence: 99%

“…For instance, Lim et al analysed genetic alterations of EGFR pathway in 46 patients with HCC, they found that patients treated with lenvatinib have an increasing trend in the number of EGFR and ERBB2 gene mutations, indicating that this change is a response to lenvatinib. 26 He et al performed comparative analyses of various cell lines (Hep3B, Huh7, JHH4, and HepG2), they found that lenvatinib significantly downregulated ERK phosphorylation in most HCC cell lines; however, when cells became lenvatinib-resistant (LR), they exhibited higher levels of EGFR phosphorylation compared with their parent cells. 15 A recent study showed compensatory activation of EGFR in LR cells, although this RTK is not a target of lenvatinib.…”

Section: Egfr-related Pathwaysmentioning

confidence: 99%

Lenvatinib in hepatocellular carcinoma: Resistance mechanisms and strategies for improved efficacy

Qin,

Han,

et al. 2024

Liver International

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Hepatocellular carcinoma (HCC), one of the most prevalent and destructive causes of cancer‐related deaths worldwide, approximately 70% of patients with HCC exhibit advanced disease at diagnosis, limiting the potential for radical treatment. For such patients, lenvatinib, a long‐awaited alternative to sorafenib for first‐line targeted therapy, has become a key treatment. Unfortunately, despite some progress, the prognosis for advanced HCC remains poor because of drug resistance development. However, the molecular mechanisms underlying lenvatinib resistance and ways to relief drug resistance in HCC are largely unknown and lack of systematic summary; thus, this review not only aims to explore factors contributing to lenvatinib resistance in HCC, but more importantly, summary potential methods to conquer or mitigate the resistance. The results suggest that abnormal activation of pathways, drug transport, epigenetics, tumour microenvironment, cancer stem cells, regulated cell death, epithelial–mesenchymal transition, and other mechanisms are involved in the development of lenvatinib resistance in HCC and subsequent HCC progression. To improve the therapeutic outcomes of lenvatinib, inhibiting acquired resistance, combined therapies, and nano‐delivery carriers may be possible approaches.

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A MYC-STAMBPL1-TOE1 positive feedback loop mediates EGFR stability in hepatocellular carcinoma

Zhang,

Wang,

Zhang

et al. 2024

Cell Reports

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EGFR/ERBB2 Amplifications and Alterations Associated With Resistance to Lenvatinib in Hepatocellular Carcinoma

Cited by 12 publications

References 10 publications

New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma—Today and Tomorrow

New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma—Today and Tomorrow

Lenvatinib in hepatocellular carcinoma: Resistance mechanisms and strategies for improved efficacy

A MYC-STAMBPL1-TOE1 positive feedback loop mediates EGFR stability in hepatocellular carcinoma

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