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Simple Summary Although the use of stereotactic body radiation therapy (SBRT) in the management of hepatocellular carcinoma (HCC) remains unclear, it is a therapeutic option often considered in patients not eligible to or recurring after other local therapies. Liver SBRT can be delivered using a wide range of techniques and linear accelerators. We report the first evaluation for HCC of SBRT using volumetric modulated arc therapy (VMAT) and real-time adaptive tumor gating, which is a mainly completely non-invasive procedure (no fiducial markers for 65.2% of the patients). Our study showed that this SBRT technique has very favorable outcomes with optimal local control and a low toxicity rate. Abstract Liver SBRT is a therapeutic option for the treatment of HCC in patients not eligible for other local therapies. We retrospectively report the outcomes of a cohort of consecutive patients treated with SBRT for HCC at the Montpellier Cancer Institute. Between March 2013 and December 2018, 66 patients were treated with image-guided liver SBRT using VMAT and real-time adaptive tumor gating in our institute. The main endpoints considered in this study were local control, disease-free survival, overall survival, and toxicity. The median follow-up was 16.8 months. About 66.7% had prior liver treatment. Most patients received 50 Gy in five fractions of 10 Gy. No patient had local recurrence. Overall survival and disease-free survival were, respectively, 83.9% and 46.7% at one year. In multivariate analysis, the diameter of the lesions was a significant prognostic factor associated with disease-free survival (HR = 2.57 (1.19–5.53) p = 0.02). Regarding overall survival, the volume of PTV was associated with lower overall survival (HR = 2.84 (1.14–7.08) p = 0.025). No grade 3 toxicity was observed. One patient developed a grade 4 gastric ulcer, despite the dose constraints being respected. Image-guided liver SBRT with VMAT is an effective and safe treatment in patients with inoperable HCC, even in heavily pre-treated patients. Further prospective evaluation will help to clarify the role of SBRT in the management of HCC patients.

Simple Summary Colorectal cancer (CRC) is a heterogeneous disease that can be divided into 4 consensus molecular subtypes (CMS) according to molecular profiling. The CMS classification is now considered as a reference framework for understanding the heterogeneity of CRC and for the implementation of precision medicine. Although the contribution of YAP/TAZ signalling to CRC has been intensively studied, there is little information on its role within each CMS subtype. This article aims to provide an overview of our knowledge of YAP/TAZ in CRC through the lens of the CMS classification. Abstract Recent advance in the characterization of the heterogeneity of colorectal cancer has led to the definition of a consensus molecular classification within four CMS subgroups, each associated with specific molecular and clinical features. Investigating the signalling pathways that drive colorectal cancer progression in relation to the CMS classification may help design therapeutic strategies tailored for each CMS subtype. The two main effectors of the Hippo pathway YAP and its paralogue TAZ have been intensively scrutinized for their contribution to colon carcinogenesis. Here, we review the knowledge of YAP/TAZ implication in colorectal cancer from the perspective of the CMS framework. We identify gaps in our current understanding and delineate research avenues for future work.

Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has no effective treatment. Nucleolin targeting by the pseudopeptide N6L inhibits the tumor growth and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here, we explored the pathways regulated by nucleolin and N6L in PDAC. We demonstrated that both interact with β-catenin, and that the Wnt/β-catenin pathway is activated in PDAC mouse models. Nucleolin inhibition decreases Wnt/β-catenin pathway activation in PDAC cells and tumors, and represents a new druggable pathway regulated by nucleolin. Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and resistant cancer with no available effective therapy. We have previously demonstrated that nucleolin targeting by N6L impairs tumor growth and normalizes tumor vessels in PDAC mouse models. Here, we investigated new pathways that are regulated by nucleolin in PDAC. We found that N6L and nucleolin interact with β-catenin. We found that the Wnt/β-catenin pathway is activated in PDAC and is necessary for tumor-derived 3D growth. N6L and nucleolin loss of function induced by siRNA inhibited Wnt pathway activation by preventing β-catenin stabilization in PDAC cells. N6L also inhibited the growth and the activation of the Wnt/β-catenin pathway in vivo in mice and in 3D cultures derived from MIA PaCa2 tumors. On the other hand, nucleolin overexpression increased β-catenin stabilization. In conclusion, in this study, we identified β-catenin as a new nucleolin interactor and suggest that the Wnt/β-catenin pathway could be a new target of the nucleolin antagonist N6L in PDAC.

Simple Summary In the era of direct-acting antivirals against the hepatitis C virus (HCV), curing chronic hepatitis C has become a reality. However, while replicating chronically, HCV creates a peculiar state of inflammation and oxidative stress in the infected liver, which fuels DNA damage at the onset of HCV-induced hepatocellular carcinoma (HCC). This cancer, the second leading cause of death by cancer, remains of bad prognosis when diagnosed. This review aims to decipher how HCV durably alters elements of the extracellular matrix that compose the liver microenvironment, directly through its viral proteins or indirectly through the induction of cytokine secretion, thereby leading to liver fibrosis, cirrhosis, and, ultimately, HCC. Abstract Chronic infection by the hepatitis C virus (HCV) is a major cause of liver diseases, predisposing to fibrosis and hepatocellular carcinoma. Liver fibrosis is characterized by an overly abundant accumulation of components of the hepatic extracellular matrix, such as collagen and elastin, with consequences on the properties of this microenvironment and cancer initiation and growth. This review will provide an update on mechanistic concepts of HCV-related liver fibrosis/cirrhosis and early stages of carcinogenesis, with a dissection of the molecular details of the crosstalk during disease progression between hepatocytes, the extracellular matrix, and hepatic stellate cells.

Surgery remains the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Therefore, a predictive score for resectability on diagnosis is needed. A total of 814 patients were included between 2014 and 2017 from 15 centers included in the BACAP (the national Anatomo-Clinical Database on Pancreatic Adenocarcinoma) prospective cohort. Three groups were defined: resectable (Res), locally advanced (LA), and metastatic (Met). Variables were analyzed and a predictive score was devised. Of the 814 patients included, 703 could be evaluated: 164 Res, 266 LA, and 273 Met. The median ages of the patients were 69, 71, and 69, respectively. The median survival times were 21, 15, and nine months, respectively. Six criteria were significantly associated with a lower probability of resectability in multivariate analysis: venous/arterial thrombosis (p = 0.017), performance status 1 (p = 0.032) or ≥ 2 (p = 0.010), pain (p = 0.003), weight loss ≥ 8% (p = 0.019), topography of the tumor (body/tail) (p = 0.005), and maximal tumor size 20–33 mm (p &lt, 0.013) or &gt, 33 mm (p &lt, 0.001). The BACAP score was devised using these criteria (http://jdlp.fr/resectability/) with an accuracy of 81.17% and an area under the receive operating characteristic (ROC) curve of 0.82 (95% confidence interval (CI): 0.78, 0.86). The presence of pejorative criteria or a BACAP score &lt, 50% indicates that further investigations and even neoadjuvant treatment might be warranted. Trial registration: NCT02818829.