Are we ready for targeted therapy combinations in HCC?

Cinnamon, Einat; Pikarsky, Eli

doi:10.1136/gutjnl-2019-319780

Cited by 6 publications

(5 citation statements)

References 11 publications

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“… 1 , 2 Nearly 90% of these patients have hepatocellular carcinoma (HCC) which is the most prevalent form of primary liver cancer. 3 The number of new cases and deaths from HCC in China is well above the world average. 4 , 5 , 6 The frequency of HCC recurrence and its high metastatic capacity have restricted the 5‐year survival rate despite developments in HCC therapy over the last few decades.…”

Section: Introductionmentioning

confidence: 99%

TUG1 long non‐coding RNA enlists the USF1 transcription factor to overexpress ROMO1 leading to hepatocellular carcinoma growth and metastasis

Liu

Qiu

et al. 2020

MedComm

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Hepatocellular carcinoma (HCC) is a prevalent and highly aggressive cancer. Long non-coding RNAs (lncRNAs) are recognized as potential molecular targets for HCC and are currently under increased research focus. Here, we investigate the regulatory processes underlying the axis of the lncRNA taurine upregulated gene 1 (TUG1), Upstream Transcription Factor 1 (USF1), and reactive oxygen species modulator 1 (ROMO1) in the propagation and metastasis of HCC cells. Distribution of lncRNA TUG1 was found to be prominent in HCC cell cytoplasm and nuclei. LncRNA TUG1 conscripted the USF1 transcription factor to enhance the promoter function of ROMO1. Enlisting the USF1 transcription factor to increase ROMO1 expression following upregulation of TUG1 lncRNA enhanced HCC Huh7 cell proliferation, motility, and metastasis. Rapid tumor proliferation in nude mice provided in vivo verification. The importance of the lncRNA TUG1/USF1/ROMO1 complex as a target for HCC therapy is a key result of this investigation which is exemplified by its role in regulating the proliferation, motility, and metastasis of HCC cells.

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Section: Introductionmentioning

confidence: 99%

TUG1 long non‐coding RNA enlists the USF1 transcription factor to overexpress ROMO1 leading to hepatocellular carcinoma growth and metastasis

Liu

Qiu

et al. 2020

MedComm

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“…Despite significant advancements in HCC treatment in recent years, including the development of multikinase inhibitors (MKIs) such as lenvatinib, cabozantinib, and regorafenib, approved for advanced or metastatic HCC treatment, the options for available therapeutic strategies for these patients remain limited [ 5 – 7 ]. Furthermore, a significant number of HCC patients continue to experience a lack of durable and optimal clinical benefits, even when utilizing these new treatment alternatives [ 6 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Enhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition

Han,

Ling,

Wang

et al. 2023

Cancer Cell Int

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Hepatocellular carcinoma (HCC) is a malignancy with high morbidity and mortality but lacks effective treatments thus far. Although the emergence of immune checkpoint inhibitors in recent years has shed light on the treatment of HCC, a considerable number of patients are still unable to achieve durable and ideal clinical benefits. Therefore, refining the combination of immune checkpoint inhibitors (ICIs) to enhance the therapeutic effect has become a global research hotspot. Several histone deacetylase 2 inhibitors have shown advantages in ICIs in many solid cancers, except for HCC. Additionally, the latest evidence has shown that histone deacetylase 2 inhibition can regulate PD-L1 acetylation, thereby blocking the nuclear translocation of PD-L1 and consequently enhancing the efficacy of PD-1/PD-L1 inhibitors and improving anti-cancer immunity. Moreover, our team has recently discovered a novel HDAC2 inhibitor (HDAC2i), valetric acid (VA), that possesses great potential in HCC treatment as a monotherapy. Thus, a new combination strategy, combining HDAC2 inhibitors with ICIs, has emerged with significant development value. This perspective aims to ignite enthusiasm for exploring the application of ideal HDAC2 inhibitors with solid anti-tumor efficacy in combination with immunotherapy for HCC.

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“…MKIs such as lenvatinib, cabozantinib, and regorafenib have been approved for treating advanced or metastatic HCC ( 6 – 8 ). However, a considerable number of HCC patients are still unable to gain durable and ideal clinical benefits ( 7 – 10 ).…”

Section: Introductionmentioning

confidence: 99%

CAXII inhibitors: Potential sensitizers for immune checkpoint inhibitors in HCC treatment

Han

Hony³

et al. 2023

Front. Immunol.

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Hepatocellular carcinoma (HCC) is a lethal malignancy with a lack of effective treatments particularly for the disease at an advanced stage. Even though immune checkpoint inhibitors (ICIs) have made great progress in the treatment of HCC, durable and ideal clinical benefits still cannot be achieved in plenty of patients with HCC. Therefore, novel and refined ICI-based combination therapies are still needed to enhance the therapeutic effect. The latest study has reported that the carbonic anhydrase XII inhibitor (CAXIIi), a novel type of anticancer drug, can modify the tumor immunosuppression microenvironment by affecting hypoxic/acidic metabolism and alter the functions of monocytes and macrophages by regulating the expression of C-C motif chemokine ligand 8 (CCL8). These observations shine a light on improving programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1) immunotherapy in combination with CAXIIis. This mini-review aims to ignite enthusiasm to explore the potential application of CAXIIis in combination with immunotherapy for HCC.

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Are we ready for targeted therapy combinations in HCC?

Cited by 6 publications

References 11 publications

TUG1 long non‐coding RNA enlists the USF1 transcription factor to overexpress ROMO1 leading to hepatocellular carcinoma growth and metastasis

TUG1 long non‐coding RNA enlists the USF1 transcription factor to overexpress ROMO1 leading to hepatocellular carcinoma growth and metastasis

Enhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition

CAXII inhibitors: Potential sensitizers for immune checkpoint inhibitors in HCC treatment

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