Liver Organoids as an In Vitro Model to Study Primary Liver Cancer

Siervi, Silvia De; Turato, Cristian

doi:10.3390/ijms24054529

Cited by 12 publications

(8 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Liver organoids can represent an ideal approach due to their ability to retain the morphological properties of primary tissue and to assess different biological features, including proliferation, signaling, and cell-cell interaction. 43 …”

Section: Resultsmentioning

confidence: 99%

VDAC1-interacting molecules promote cell death in cancer organoids through mitochondrial-dependent metabolic interference

Conti Nibali,

De Siervi,

Luchinat

et al. 2024

iScience

Self Cite

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

VDAC1-interacting molecules promote cell death in cancer organoids through mitochondrial-dependent metabolic interference

Conti Nibali,

De Siervi,

Luchinat

et al. 2024

iScience

Self Cite

View full text Add to dashboard Cite

“…The absence of appropriate in vitro models that accurately represent the cancer biology and heterogeneity of patients is a significant barrier to the development of new therapies and biomarkers for iCCA. Due to their ability to retain the morphological properties of primary tissue and assess different biological features, including proliferation, signaling, and cell-cell interaction, liver organoids could represent an ideal approach (De Siervi and Turato, 2023).…”

Section: Resultsmentioning

confidence: 99%

VDAC1 selective molecules promote patients’-derived cancer organoids death through mitochondrial-dependent metabolic interference

Conti Nibali,

De Siervi,

Luchinat

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

In the continuous pursuit of advanced cancer therapeutics, our research unveils the potential to selectively target Voltage-Dependent Anion-selective Channel isoform 1 (VDAC1), a pivotal component in cellular metabolism and apoptosis. VDAC1’s role in metabolic rewiring and its subsequent prominence in many cancer types offer a unique intervention point. The incorporation of a systematic,in silicotoin vitromethodology identified novel VA (VDAC-Antagonist) molecules with the capability to selectively bind to VDAC1, displaying a substantial specificity towards cancer cells while sparing healthy ones.This research first led to the revelation of a specialized VDAC1 pocket, which accommodates the binding of these VA molecules, thereby instigating a selective displacement of NADH. The coenzyme is a critical metabolic substrate, and its displacement ensues in notable mitochondrial distress and a reduction in cell proliferation, specifically in cancer cells. Furthermore, meticulous analysis using organoids derived from intrahepatic cholangiocarcinoma patients (iCCA) demonstrated a dose-dependent reduction in cell viability upon treatment with VA molecules, correlating with the findings from commercial cell lines.Interestingly, VA molecules significantly reduced cell viability and demonstrated a lower impact on healthy cells than conventional treatments like gemcitabine. This differential impact is possibly due to the elevated expression of VDAC1 in various cancer cell lines, rendering them more susceptible to metabolic disruptions induced by VA molecules.This endeavor uncovers a multifaceted approach to cancer treatment, involving meticulous targeting of metabolic gatekeepers like VDAC1 using novel entities, thereby paving the way for developing more selective and refined cancer therapeutics. The identified VA molecules, albeit in the nascent stages, represent promising candidates for further optimization and development, potentially revolutionizing treatment modalities in cancer therapy through precise metabolic interventions.

show abstract

“…3 Intrahepatic cholangiocarcinoma, hepatocellular carcinoma (HCC), and combined hepatocellular-cholangiocarcinoma are the primary liver malignancies, which are tumors that grow directly in the organ as opposed to as a result of metastasis. 4 Hepatocellular carcinoma is caused by the malignant transformation of hepatocytes, accounting for 85-90% of primary liver cancer cases. The mortality rate continues to increase, and the 5 year relative survival rate is just 18%, with only pancreatic cancer having a lower mortality rate.…”

Section: Introductionmentioning

confidence: 99%

“…More than 1 million people a year are predicted to be impacted by liver cancer by 2025 3 . Intrahepatic cholangiocarcinoma, hepatocellular carcinoma (HCC), and combined hepatocellular‐cholangiocarcinoma are the primary liver malignancies, which are tumors that grow directly in the organ as opposed to as a result of metastasis 4 . Hepatocellular carcinoma is caused by the malignant transformation of hepatocytes, accounting for 85–90% of primary liver cancer cases.…”

Section: Introductionmentioning

confidence: 99%

Identification of secretory pathway‐related genes based on Random Forest algorithm to predict the prognosis and immunotherapy response of hepatocellular carcinoma

Wang,

Shi,

Huang

et al. 2023

The Journal of Gene Medicine

View full text Add to dashboard Cite

BackgroundThe dysfunction of secretory pathways may represent biomarkers or therapeutic targets of cancer. The hepatocellular carcinoma (HCC) phenotype was studied in relation to the genes in the secretory pathway and to screen for a combination of genes that may be a viable therapeutic target for HCC and connected to the pathophysiological features of the tumor.MethodsUsing the HCC information from The Cancer Genome Atlas, somatic mutation and prognostic association analysis were performed on the secretory pathway genes. Based on prognostic genes in the secretory pathway, the samples were consensus clustered, and a Random Forest model was built. The clinical characteristics, tumor mutation burden, functional status and potential responses to immunotherapy and tumor suppressor medications of various subtypes and risk groups were discussed.ResultsOf the 84 genes for secretory pathway, 32 were prognostic genes related to HCC, which divided HCC into two categories: C1 and C2. By comparing the two types of HCC samples, it was found that the survival outcome of C1 was inferior, with stronger adaptive and innate immunity, but less sensitive to immunotherapy than C2. The constructed prognostic signature included seven of the 32 prognostic genes in the secretory pathway, which showed significant correlation with the prognosis, somatic mutation, biological pathway status, potential response to immunotherapy and sensitivity of 72 tumor suppressor drugs from different HCC cohorts, and had a feasible prognostic effect for 31 types of cancer and immunotherapy cohorts.ConclusionsIn this study, HCC was divided into two molecular subtypes according to prognostic genes in the secretory pathway, and seven of them were combined into one signature, which produced significant results in evaluating the prognosis of different HCC cohorts, pan‐cancer cohorts and immunotherapy cohorts, and had potential guiding significance for prophylactic immunotherapy in patients with HCC.

show abstract

Liver Organoids as an In Vitro Model to Study Primary Liver Cancer

Cited by 12 publications

References 110 publications

VDAC1-interacting molecules promote cell death in cancer organoids through mitochondrial-dependent metabolic interference

VDAC1-interacting molecules promote cell death in cancer organoids through mitochondrial-dependent metabolic interference

VDAC1 selective molecules promote patients’-derived cancer organoids death through mitochondrial-dependent metabolic interference

Identification of secretory pathway‐related genes based on Random Forest algorithm to predict the prognosis and immunotherapy response of hepatocellular carcinoma

Contact Info

Product

Resources

About