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    Home > Active Ingredient News > Antitumor Therapy > Cell Death Dis: The expression level of BH3-only protein determines the response of hepatocellular carcinoma patients to sorafenib-based drug combination therapy

    Cell Death Dis: The expression level of BH3-only protein determines the response of hepatocellular carcinoma patients to sorafenib-based drug combination therapy

    • Last Update: 2021-07-30
    • Source: Internet
    • Author: User
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    Hepatocellular carcinoma (HCC) is a serious global health problem.
    The incidence of the disease is increasing year by year and treatment options are limited

    .
    Available treatment options for patients with advanced HCC include TKI (tyrosine kinase inhibitor) sorafenib (sorafenib) and lenvatinib (lenvatinib), which mainly target VEGFR1-3, FGFR1-4, PDGFR, RET and KIT
    .
    So far, these TKI treatments are still the most effective single-agent treatment strategies for HCC

    .

    Hepatocellular carcinoma (HCC) is a serious global health problem.
    The incidence of the disease is increasing year by year and treatment options are limited

    .
    Hepatocellular carcinoma (HCC) is a serious global health problem.
    The incidence of the disease is increasing year by year and treatment options are limited

    .

    Recently, a combination therapy of atezolizumab (anti-PDL1) and bevacizumab (anti-VEGF) , an immune checkpoint inhibitor, has been approved as a first-line therapy for advanced HCC
    .

    immunity


    Compared with sorafenib monotherapy, this combination therapy strategy can increase the progression-free survival of patients
    .
    Therefore, in order to improve the survival rate of HCC patients, it is particularly important to understand the relevant mechanisms of treatment resistance and identify the corresponding molecular targets, which will also help formulate effective individualized treatment strategies
    .


    Compared with sorafenib monotherapy, this combination therapy strategy can increase the progression-free survival of patients
    .
    Compared with sorafenib monotherapy, this combination therapy strategy can increase the progression-free survival of patients
    .


    In this study, the researchers analyzed different HCC cell lines and HCC tissues from different patients with heterogeneity to investigate whether the therapeutic response of sorafenib can be enhanced by combining with pro-apoptotic drugs, such as TRAIL ( TNF-related apoptosis-inducing ligand) or BH3 mimic ABT-737, which target the death receptor and mitochondrial pathway of apoptosis, respectively
    .


    Sorafenib and TRAIL-induced cell death

    Sorafenib and TRAIL-induced cell death

    The researchers found that these two drugs can enhance the cell death effect induced by sorafenib, but this depends on the specific BH3-only protein
    .
    TRAIL can only enhance sorafenib-induced cell death in NOXA-expressing HCC cells, while ABT-737 can also enhance this response in NOXA-deficient cells

    .
    However, in the absence of BIM expression, ABT-737 does not enhance the cytotoxicity of sorafenib, even if NOXA is significantly expressed

    .


    In the presence of NOXA, BIM-deficient HCC cells can in turn be significantly sensitive to cell death through the combination of sorafenib and TRAIL
    .
    Compared to HCC tissues resistant to the combination of sorafenib and TRAIL treatment, HCC tissues sensitive to the treatment group showed increased expression of NOXA
    .


    Compared to HCC tissues resistant to the combination of sorafenib and TRAIL treatment, HCC tissues sensitive to the treatment group showed increased expression of NOXA
    .
    Compared to HCC tissues resistant to the combination of sorafenib and TRAIL treatment, HCC tissues sensitive to the treatment group showed increased expression of NOXA
    .

    Sorafenib reduces the proliferation of Huh7 cells

    Sorafenib reduces the proliferation of Huh7 cells

    All in all, the results of this study show that the expression of BH3-only protein determines the therapeutic response of HCC to different sorafenib drug combinations
    .
    Therefore, individual analysis of BH3-only protein expression levels may help stratify certain TKI-based HCC treatment strategies
    .

    The results of this study indicate that the expression of BH3-only protein determines the therapeutic response of HCC to different sorafenib drug combinations
    .
    The results of this study indicate that the expression of BH3-only protein determines the therapeutic response of HCC to different sorafenib drug combinations
    .


    Original source:


    Busche, S.
    , John, K.
    , Wandrer, F.
    et al.
    BH3-only protein expression determines hepatocellular carcinoma response to sorafenib-based treatment.
    Cell Death Dis 12, 736 (26 July 2021).

    BH3-only protein expression determines hepatocellular carcinoma response to sorafenib-based treatment.

     



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