Hepatic Oncology最新文献

For almost a decade, systemic therapy of advanced hepatocellular carcinoma (HCC) was limited to the tyrosine kinase inhibitor (TKI) sorafenib. Different agents including checkpoint inhibitors, TKIs and anti-VEGFR antibodies demonstrated efficacy in treatment. For the first time, the combination of atezolizumab and bevacizumab, a first-line treatment that is superior to the current standard was identified, potentially changing the way we treat HCC. In this review, we summarize current data on systemic treatment of patients with advanced HCC, focusing on combination therapies comprising immune checkpoint inhibitors, TKIs and locoregional therapies. We elucidate findings from recent trials and discuss such challenges as the lack of predictive biomarkers for identification of subgroups that will benefit from novel treatment strategies.

This review highlights two rare entities that are predominantly seen in children: hepatic mesenchymal hamartoma (HMH) and undifferentiated embryonal sarcoma of the liver (UESL). HMH is a benign lesion predominantly seen in the first 2 years of life, while UESL is malignant and usually identified in patients between 6 and 10 years of age. UESL may arise in the background of HMH, and the association has been supported by similar chromosomal aberrations (19q13.4). The diagnosis of both lesions is primarily based on histologic evaluation, as the clinical and radiological features are not always typical. The clinicopathologic characteristics, pathogenesis, differential diagnoses and treatment for both lesions are discussed.

Discussing the importance of patient advocacy and the advancement of systemic therapies for the treatment of liver cancer, we catch up with Hepatic Oncology's latest editorial board member Ghassan Abou-Alfa.

Liver cancer is the second most lethal cancer in the world with limited treatment options. Hepatocellular carcinoma (HCC), which accounts for more than 80% of all liver cancers, has had increasing global incidence over the past few years. There is an urgent need for novel and better therapeutic intervention for HCC patients. The JAK/STAT signaling pathway plays a multitude of important biological functions in both normal and malignant cells. In a subset of HCC, JAK/STAT signaling is aberrantly activated, leading to dysregulation of downstream target genes that controls survival, angiogenesis, stemness, immune surveillance, invasion and metastasis. In this review, we will focus on the role of JAK/STAT signaling in HCC and discuss the current clinical status of several JAK/STAT inhibitors.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Most patients present with advanced or metastatic HCC at diagnosis and face a dismal prognosis. Tyrosine kinases are the gold standard treatment for this disease but yield limited survival benefits. Immune checkpoint inhibitors that augment adaptive immunity have been tested in HCC. Complex interactions between tumor cells, lymphocytes and the tumor environment determine the efficacy of such immunotherapies. Innate immune mechanisms - known drivers of liver disease progression in pre-HCC conditions such as fibrosis or cirrhosis - may either support or counteract tumor-related immune activation. In this review, we will highlight current concepts of the role of the innate immune system in hepatocarcinogenesis and discuss their relevance for translation into clinics.

Colorectal cancer is a worldwide public health issue, presenting an advanced stage at diagnosis in more than 20% of patients. Liver metastases are the most common metastatic sites and are not indicated for resection in 80% of cases. Unresectable colorectal cancer liver metastases that are refractory to systemic chemotherapy may benefit from transarterial chembolization with irinotecan-loaded beads (DEBIRI). Several studies show the safety and efficacy of DEBIRI for the treatment of colorectal cancer liver metastases. The development of transarterial chembolization and the introduction of new embolics have contributed to better outcomes of DEBIRI. This article reviews the current literature on DEBIRI reporting its use, efficacy in terms of tumor response and survival and side effects.

Aim: Histone-modifiable lysine-specific demethylase-1 (LSD1/KDM1A) is an oncoprotein upregulated in cancers, including hepatoma. We previously reported that the hepatoma-preventive geranylgeranoic acid (GGA) inhibits KDM1A at the same IC₅₀ as that of the clinically used tranylcypromine. Here, we report that these inhibitors induce the cytoplasmic translocation of nuclear KDM1A in a human hepatoma-derived cell line.

Methods & results: Immunofluorescence studies revealed that KDM1A was cytoplasmically localized in HuH-7 cells 3 h after GGA or tranylcypromine addition. However, GGA did not affect the subcellular localization of another histone lysine-specific demethylase, KDM5A. This suggests that GGA-induced translocation is KDM1A specific.

Conclusion: These data demonstrate, for the first time, that KDM1A inhibitors specifically induce the cytoplasmic translocation of nuclear KDM1A.

Most hepatocellular carcinoma patients could not benefit from or experience disease recurrence after curative treatments. In 2007 sorafenib demonstrated efficacy in first line treatment of advanced hepatocellular carcinoma. After a decade of negative trials, in early 2019 we now have another tyrosine kinase inhibitor available in first line, lenvatinib, three other targeted therapies in second line post-sorafenib (regorafenib, cabozantinib and ramucirumab) and promising data from two immunotherapies (nivolumab and pembrolizumab). Unfortunately, no biomarkers have been identified to help guide our choice. In this short review we summarize the results of these different therapies and propose a therapeutic algorithm based on subgroup analysis. It is most likely that we will not have head-to-head comparisons in second line trials.