Hepatocellular carcinoma (HCC) remains the sixth most commonly diagnosed malignancy worldwide, still representing an important cause of cancer-related death. Over the next few years, novel systemic ...treatment options have emerged. Among these, immune checkpoint inhibitors (ICIs) have been widely evaluated and are under assessment, as monotherapy or in combination with other anticancer agents in treatment-naïve and previously treated patients. In particular, the approval of the PD-L1 inhibitor atezolizumab plus the antiangiogenic agent bevacizumab as front-line treatment for advanced HCC has led to the adoption of this combination in this setting, and the IMbrave 150 phase III trial has established a novel standard of care. However, several questions remain unanswered, including the identification of reliable predictors of response to ICIs in HCC patients. In the current paper, we will provide an updated overview of potentially useful predictive biomarkers of response to immunotherapy in advanced HCC. A literature search was conducted in September 2021 of Pubmed/Medline, Cochrane library and Scopus databases.
Recent pieces of evidence have emerged on the relevance of microorganisms in modulating responses to anticancer treatments and reshaping the tumor-immune microenvironment. On the one hand, many ...studies have addressed the role of the gut microbiota, providing interesting correlative findings with respect to etiopathogenesis and treatment responses. On the other hand, intra-tumoral bacteria are being recognized as intrinsic and essential components of the cancer microenvironment, able to promote a plethora of tumor-related aspects from cancer growth to resistance to chemotherapy. These elements will be probably more and more valuable in the coming years in early diagnosis and risk stratification. Furthermore, microbial-targeted intervention strategies may be used as adjuvants to current therapies to improve therapeutic responses and overall survival. This review focuses on new insights and therapeutic approaches that are dawning against pancreatic cancer: a neoplasm that arises in a central metabolic "hub" interfaced between the gut and the host.
Recent next-generation sequencing (NGS) studies on large cohorts of cholangiocarcinoma (CCA) patients have clearly revealed the extreme intra- and inter-tumoral molecular heterogeneity that ...characterizes this malignancy. The lack of a stereotyped molecular signature in CCA makes the identification of actionable therapeutic targets challenging, making it mandatory to have a better understanding of the origin of such heterogeneity in order to improve the clinical outcome of these patients. Compelling evidence has shown that the CCA genomic landscape significantly differs according to anatomical subtypes and the underlying etiology, highlighting the importance of conducting molecular studies in different populations of CCA patients. Currently, some risk factors have been recognized in CCA development, while others are emerging from recent epidemiological studies. Nevertheless, the role of each etiologic factor in driving CCA genetic heterogeneity still remains unclear, and available studies are limited. In an attempt to shed more light on this issue, here we review the current literature data on the mutational spectrum of this disease according to different etiologies.
Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy associated with poor prognosis and a 5-year survival rate of 12%. Many drugs have been tested over the years with conflicting ...results. The aim of this review is to provide an overview of current therapies in MPM and how to best interpret the data available on these drugs. Furthermore, we focused on promising treatments under investigation, such as immunotherapy with targets different from anti-PD-1/PD-L1 inhibitors, vaccines, target therapies, and metabolism-based strategies.
Cholangiocarcinoma (CCA) is a rare, aggressive disease with poor overall survival. In advanced cases, surgery is often not possible or fails; in addition, there is a lack of effective and specific ...therapies. Multidisciplinary approaches and advanced technologies have improved the knowledge of CCA molecular pathogenesis, highlighting its extreme heterogeneity and high frequency of genetic and molecular aberrations. Effective preclinical models, therefore, should be based on a comparable level of complexity. In the past years, there has been a consistent increase in the number of available CCA models. The exploitation of even more complex CCA models is rising. Examples are the use of CRISPR/Cas9 or stabilized organoids for in vitro studies, as well as patient-derived xenografts or transgenic mouse models for in vivo applications. Here, we examine the available preclinical CCA models exploited to investigate: (i) carcinogenesis processes from initiation to progression; and (ii) tools for personalized therapy and innovative therapeutic approaches, including chemotherapy and immune/targeted therapies. For each model, we describe the potential applications, highlighting both its advantages and limits.
•Although radical surgical resection represents the only potentially curative treatment for cholangiocarcinoma, the majority of patients is diagnosed with unresectable disease.•Neoadjuvant treatment ...has been explored in this setting, in order to increase R0 resection rate and to provide long-term survival.•However, few data are available so far in extrahepatic as well as in intrahepatic cholangiocarcinoma.•In this review, we will provide an overview on neoadjuvant treatment in this setting.
Biliary tract cancers (BTCs) comprise a heterogenous group of aggressive and rare malignancies arising in the bile duct outside or within the liver. BTCs include cholangiocarcinoma (CCA), gallbladder cancer (GBC) and ampulla of Vater cancer (AVC); according to the “historical” anatomical classification, CCAs are further subdivided into extrahepatic cholangiocarcinomas (eCCAs) – including distal (dCCA) and perihilar (pCCA) - and intrahepatic cholangiocarcinomas (iCCA). Notably enough, these subtypes reflect distinct features in terms of biology, epidemiology, prognosis and therapeutic strategies. Although surgical resection remains the only potentially curative treatment option for CCA patients, radical surgery is possible for only a small proportion of cases. Moreover, it has been observed that up to 50% of patients deemed resectable at diagnosis are found to be unresectable during exploratory laparotomy. Additionally, even following radical surgery, recurrence rates are high. Neoadjuvant therapy represents an appealing approach in this setting, where this therapeutic strategy has the potential to improve local and distant control, to achieve R0 resection and to prevent distant metastasis. However, few data are currently available supporting neoadjuvant therapy in CCA and several questions remains unanswered, including the activity of systemic therapy in early stages of the disease, the optimal start time of treatment, patient selection and the length of neoadjuvant therapy. In this review, we will discuss available data on neoadjuvant systemic therapy in CCA, highlighting future directions in this setting, with a particular focus on recently published data and ongoing and recruiting trials.
Background and Aims:
Gut microbiota is involved in many physiological functions and its imbalance is associated with several diseases, particularly with inflammatory bowel diseases. Mucosa-associated ...microbiota could have a key role in induction of host immunity and in inflammatory process. Although the role of fungi has been suggested in inflammatory disease pathogenesis, the fungal microbiota has not yet been deeply explored. Here we analysed the bacterial and fungal composition of the mucosa-associated microbiota of Crohn’s disease patients and healthy subjects.
Methods:
Our prospective, observational study evaluated bacterial and fungal composition of mucosa-associated microbiota of 23 Crohn’s disease patients 16 in flare, 7 in remission and 10 healthy subjects, using 16S MiSeq and ITS2 pyrosequencing sequencing, respectively. Global fungal load was assessed by real time quantitative polymerase chain reaction.
Results:
Bacterial microbiota in Crohn’s disease patients was characterised by a restriction in biodiversity. with an increase of Proteobacteria and Fusobacteria. Global fungus load was significantly increased in Crohn’s disease flare compared with healthy subjects p < 0.05. In both groups, the colonic mucosa-associated fungal microbiota was dominated by Basidiomycota and Ascomycota phyla. Cystofilobasidiaceae family and Candida glabrata species were overrepresented in Crohn’s disease. Saccharomyces cerevisiae and Filobasidium uniguttulatum species were associated with non-inflamed mucosa, whereas Xylariales order was associated with inflamed mucosa.
Conclusions:
Our study confirms the alteration of the bacterial microbiota and is the first demonstration of the existence of an altered fungal microbiota in Crohn’s disease patients, suggesting that fungi may play a role in pathogenesis.
Surgical resection is the only option of cure for patients with metastatic colorectal cancer (CRC). However, the risk of recurrence within 18 mo after metastasectomy is around 75% and the liver is ...the most frequent site of relapse. The current international guidelines recommend an adjuvant therapy after surgical resection of CRC metastases despite the lower level of evidence (based on the quality of studies in this setting). However, there is still no standard treatment and the effective role of an adjuvant therapy remains controversial. The aim of this review is to report the state-of-art of systemic chemotherapy and regional chemotherapy with hepatic arterial infusion in the management of patients after resection of metastases from CRC, with a literature review and meta-analysis of the relevant randomized controlled trials.
There is a relative lack of evidence about systemic treatments in patients with hepatocellular carcinoma (HCC) and moderate liver dysfunction (Child-Pugh B). In this multicenter study we ...retrospectively analyzed data from Child-Pugh B-HCC patients naïve to systemic therapies, treated with MC or best supportive care (BSC). To reduce the risk of selection bias, an inverse probability of treatment weighting approach was adopted. Propensity score was generated including: extrahepatic spread; macrovascular invasion; performance status, alphafetoprotein > 400 ng/ml, Child- Pugh score B7 vs. B8-9. We identified 35 MC-treated patients and 70 controls. Median overall survival was 7.5 95% CI: 3.733-11.267in MC-patients and 5.1 months 95% CI: 4.098-6.102 in the BSC group (p = 0.013). In patients treated with MC, median progression-free survival was 4.5 months (95% CI: 2.5-6.5). The univariate unweighted Cox regression showed a 42% reduction in death risk for patients on MC (95%CI: 0.370-0.906; p = 0.017). After weighting for potential confounders, death risk remained essentially unaltered. In the MC group, 12 patients (34.3%) experienced at least one adverse event, the most common of which were: fatigue (17.1%), hand-foot syndrome (8.5%), thrombocytopenia (8.5%), and neutropenia (5.7%). MC seems a safe option for Child-Pugh B-HCC patients. Its potential antitumour activity warrants prospective evaluations.
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