Classic versus innovative strategies for immuno-therapy in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a dismal prognosis. Immunotherapy with immune checkpoint inhibitors (ICIs), either as monotherapy, in combination with other ICIs, or alongside chemotherapy, has significantly improved outcomes in several solid tumors. However, its efficacy in PDAC remains limited due to multiple resistance mechanisms.

Etiology of Hepatocellular Carcinoma May Influence the Pattern of Progression under Atezolizumab-Bevacizumab.

Background: Preclinical models have shown that metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC) may exhibit reduced responsiveness to immunotherapy, especially for intrahepatic lesions due to liver tumor microenvironment. Radiological pattern of progression has been validated in clinical studies as a useful tool for predicting outcomes in HCC undergoing systemic treatments.

Aims: The aim of this study was to determine whether MASLD influences the pattern of progression in patients treated with atezolizumab-bevacizumab.

Molecular hydrogen therapy: A "democratic" emerging strategy against aging and age-related diseases.

Aging represents the main risk factor for the development of several diseases, including cardiovascular and metabolic conditions, neurodegenerative disorders and cancer. As the number of elderly people is increasing worldwide, different strategies to counteract age-related diseases have been investigated. Recently, the use of molecular hydrogen (H) as a preventive and therapeutic approach has been proposed due to its antioxidant and anti-inflammatory properties, its ability to regulate cell senescence and death, and to restore intestinal eubiosis.

Mutant p53 Associates with Human Equilibrative Nucleoside 1 Upregulation and Better Response to Adjuvant Gemcitabine in Intrahepatic Cholangiocarcinoma Patients.

The prognostic and predictive role of the human equilibrative nucleoside transporter 1 (hENT-1) has emerged in different cancer types, including intrahepatic cholangiocarcinoma (iCCA), but the mechanisms regulating its expression are poorly understood. Here, we investigated the link between p53 status and hENT-1 regulation in 38 iCCA patients and cell line models; the predictive role of p53 status in response to adjuvant gemcitabine was also investigated. A positive association between mutant p53 cells and hENT-1 expression was observed in iCCA tissue samples; furthermore, patients receiving adjuvant gemcitabine and expressing mutant p53 cells > 4% in tumor tissue had a longer disease-free survival (DFS) than patients expressing mutant p53 cells ≤ 4% (median 18.

Camrelizumab in combination with chemotherapy and targeted therapy improves the prognosis in patients with advanced biliary tract cancer: a single-center retrospective clinical study.

Background: Biliary tract cancer (BTC) is an aggressive neoplasm with poor overall survival. Chemotherapy has improved the prognosis of BTC, but the outcomes still remain very unsatisfactory. Immune checkpoint inhibitor (ICI) therapy has shown promising efficacy in multiple solid tumors, including BTC.

Case Report: Long lasting response with TKI for combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer, with intermediate biological characteristics between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Given its rarity and the lack of robust data from randomized clinical trials, treatment is not standardized, and the choice on how to best manage the disease is left to the expertise of each institution. In the metastatic setting, given the more aggressive behavior of the CCA component, the usual approach is to start treatment with chemotherapy instead of tyrosine-kinase inhibitors (TKIs).

Treatment Sequencing and Independent Outcomes of First- and Second-Line Chemotherapy in a Retrospective Series of Patients with Biliary Tract Cancer.

Biliary tract cancers (BTCs) are aggressive neoplasms with limited therapeutic options. The amount of prospective evidence is poor, and limited data are available on the impact of treatment sequencing on survival. Here we report a real-world experience of patients with advanced BTC treated with at least three lines of therapy.

Chemoradiation of locally advanced biliary cancer: A PRISMA-compliant systematic review.

Introduction: Biliary tract cancers (BTC) are rare and aggressive neoplasms. The current management of locally advanced or unresectable BTC is primarily based on chemotherapy (CHT) alone, linked to a median overall survival (OS) of approximately 12 months. However, international guidelines still consider concurrent chemoradiation (CRT) as an alternative treatment option.

Viral Hepatitis in Western Patients with Advanced Intrahepatic Cholangiocarcinoma: Retrospective Assessment of Prevalence, Prognostic and Predictive Significance.

Despite a biologically established causative role of viral hepatitis (VH), i.e. HBV and HCV infections, on intrahepatic cholangiocarcinoma (ICC), only few large Western cohorts exploring the association between VH and ICC development are available.

Hepatocellular Carcinoma Immunotherapy: Predictors of Response, Issues, and Challenges.

Immune checkpoint inhibitors (ICIs), such as durvalumab, tremelimumab, and atezolizumab, have emerged as a significant therapeutic option for the treatment of hepatocellular carcinoma (HCC). In fact, the efficacy of ICIs as single agents or as part of combination therapies has been demonstrated in practice-changing phase III clinical trials. However, ICIs confront several difficulties, including the lack of predictive biomarkers, primary and secondary drug resistance, and treatment-related side effects.

Tumor Immune Microenvironment in Intrahepatic Cholangiocarcinoma: Regulatory Mechanisms, Functions, and Therapeutic Implications.

Treatment options for intrahepatic cholangiocarcinoma (iCCA), a highly malignant tumor with poor prognosis, are limited. Recent developments in immunotherapy and immune checkpoint inhibitors (ICIs) have offered new hope for treating iCCA. However, several issues remain, including the identification of reliable biomarkers of response to ICIs and immune-based combinations.

Suboptimal outcomes of sorafenib as a second-line treatment after atezolizumab-bevacizumab for unresectable hepatocellular carcinoma.

Background: Most patients receiving atezolizumab-bevacizumab (AB) for hepatocellular carcinoma will eventually experience disease progression. Randomized clinical trials (RCTs) are undergoing to identify second-line treatments. Where RCTs are unavailable or patients are non-eligible, sorafenib is often prescribed based on approval and reimbursement policies.

Intestinal Microbiota Increases Cell Proliferation of Colonic Mucosa in Human-Flora-Associated (HFA) Mice.

Intestinal epithelium renewal strictly depends on fine regulation between cell proliferation, differentiation, and apoptosis. While murine intestinal microbiota has been shown to modify some epithelial cell kinetics parameters, less is known about the role of the human intestinal microbiota. Here, we investigated the rate of intestinal cell proliferation in C3H/HeN germ-free mice associated with human flora (HFA, n = 8), and in germ-free (n = 15) and holoxenic mice (n = 16).

Decreasing Albumin mRNA Expression in Cholangiocarcinomas along the Bile Duct Tree.

Introduction: The progressive technologies in albumin in situ hybridization (ISH) changed the routine application and the differential diagnosis of hepatic malignancies in the last years. The aim of the present work was to assess the diagnostic utility of albumin ISH on different cholangiocarcinoma (CCA) subtypes, as well as to assess how albumin production changes along the biliary tree.

Methods: Forty-five CCAs were retrospectively selected: 29 intrahepatic (15 small-duct and 14 large-duct subtypes), 7 perihilar, and 9 extrahepatic.

Durvalumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in Biliary Tract Cancer: a Real-World Retrospective, Multicenter Study.

Background: The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed cell death ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC).

Objective: The present study investigated for the first time the impact on survival of adding durvalumab to cisplatin/gemcitabine compared with cisplatin/gemcitabine in a real-world setting.

Patients And Methods: The analyzed population included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab in combination with cisplatin/gemcitabine or with cisplatin/gemcitabine alone.

Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study.

Background: Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC.

Methods: The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out.

A phase II/III randomized clinical trial of CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative chemotherapy versus immediate resection in patIents with resecTable BiliarY Tract Cancers (BTC) at high risk for recurrence: PURITY study.

Background: Biliary tract cancers (BTCs) are rare and lethal cancers, with a 5-year survival inferior to 20%(1-3). The only potential curative treatment is surgical resection. However, despite complex surgical procedures that have a remarkable risk of postoperative morbidity and mortality, the 5-year survival rate after radical surgery (R0) is 20-40% and recurrence rates are up to ~ 75%(4-6).

FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions.

Fibroblast growth factor (FGF) signalling via FGF receptors (FGFR1-4) orchestrates fetal development and contributes to tissue and whole-body homeostasis, but can also promote tumorigenesis. Various agents, including pan-FGFR inhibitors (erdafitinib and futibatinib), FGFR1/2/3 inhibitors (infigratinib and pemigatinib), as well as a range of more-specific agents, have been developed and several have entered clinical use. Erdafitinib is approved for patients with urothelial carcinoma harbouring FGFR2/3 alterations, and futibatinib and pemigatinib are approved for patients with cholangiocarcinoma harbouring FGFR2 fusions and/or rearrangements.

Treatment resistance in pancreatic and biliary tract cancer: molecular and clinical pharmacology perspectives.

Introduction: Treatment resistance poses a significant obstacle in oncology, especially in biliary tract cancer (BTC) and pancreatic cancer (PC). Current therapeutic options include chemotherapy, targeted therapy, and immunotherapy. Resistance to these treatments may arise due to diverse molecular mechanisms, such as genetic and epigenetic modifications, altered drug metabolism and efflux, and changes in the tumor microenvironment.