Adverse events in the placebo arm of SOLO2/ENGOT-Ov21 maintenance trial of olaparib in recurrent ovarian cancer.

Background: In women with platinum sensitive recurrent ovarian cancer (PSROC) undergoing maintenance treatment, adverse events (AEs) not attributable to the current treatment are not well understood. We used data from SOLO2/ENGOT-Ov21 to evaluate AEs reported in the placebo arm and to explore their longitudinal trajectories.

Methods: SOLO2/ENGOT-Ov21 (NCT01874353) randomly assigned 295 PSROC participants with a BRCA1/2 mutation to maintenance olaparib tablets (N = 196) or matching placebo (N = 99).

PARP inhibitors in gliomas: Mechanisms of action, current trends and future perspectives.

Gliomas are the most common primary malignant brain tumours in adults. Despite decades of research into novel therapeutic approaches, the prognosis remains poor. PARP1-2 are critical for DNA repair, cell survival and genomic stability and PARP inhibition (PARPi) may be a promising therapeutic approach for gliomas.

The impact of curative cancer treatment on sexual health - clinical results from the EORTC QLQ-SH22 validation study.

Background: The European Organization of Research and Treatment of Cancer (EORTC) has recently developed and validated a patient-reported outcome measure (PROM) for sexual health (SH) in cancer patients. Here, we present results from a secondary analysis of the EORTC QLQ-SH22 validation study. The objective was to investigate the impact of cancer treatment on SH over the disease trajectory into survivorship in patients who underwent curative treatment.

1-Piperidine Propionic Acid Protects from Septic Shock Through Protease Receptor 2 Inhibition.

Sepsis is a complex disorder caused by a dysregulated host response to infection, with high levels of morbidity and mortality. Treatment aimed to modulate immune response and maintain vascular function is still one of the major clinical challenges. This study was designed to test the effect of the small molecule 1-Piperidine Propionic Acid (1-PPA) as molecular targeted agent to block protease-activated receptor 2 (PAR2), one of the major modulators of inflammatory response in LPS-induced experimental endotoxemia.

KRASG12D-Mutated Metastatic Colorectal Cancer: Clinical, Molecular, Immunologic, and Prognostic Features of a New Emerging Targeted Alteration.

Purpose: KRASG12D mutation (mut) occurs in about 10%-12% of metastatic colorectal cancer (mCRC). Recently, novel KRASG12D inhibitors have been developed and are currently under investigation in phase I/II clinical trials in solid tumors including mCRC. We aimed at performing a comprehensive characterization of clinical, molecular, immunologic, and prognostic features of KRASG12D-mutated mCRC to inform the design and the interpretation of future trials.

Albumin-based strategies to effectively prolong the circulation half-life of small immunomodulatory payloads in cancer therapy.

Small immunomodulatory payloads (IMMs) such as peptide vaccines and cytokines have the capability to activate and boost the immune response against cancer. However, their clinical use has often been hindered by their poor stability and short circulating half-lives. To enhance the pharmacokinetic properties of small IMMs and promote their trafficking and accumulation in lymphatic and tumor tissues, a large variety of strategies have been developed.

Circulating Serum Micro-RNA as Non-Invasive Diagnostic Biomarkers of Endometriosis.

Background/objectives: Endometriosis (END) is a painful gynecological condition. Clinical examination, imaging, and laparoscopy can provide a definitive diagnosis of END. Nonetheless, non-invasive biomarkers could help enhance and streamline the diagnostic process.

MSI-H Detection by ddPCR in Endoscopic Ultrasound Fine Needle Biopsy (EUS-FNB) from Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited survival. Curative opportunities are only available for patients with resectable cancer. Palliative chemotherapy is the current standard of care for unresectable tumors.

The roles of arginases and arginine in immunity.

Arginase activity and arginine metabolism in immune cells have important consequences for health and disease. Their dysregulation is commonly observed in cancer, autoimmune disorders and infectious diseases. Following the initial description of a role for arginase in the dysfunction of T cells mounting an antitumour response, numerous studies have broadened our understanding of the regulation and expression of arginases and their integration with other metabolic pathways.

Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer.

High heterogeneity in clinical benefit characterizes the use of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We prospectively enrolled 113 advanced NSCLC patients treated with ICIs and performed liquid biopsy at the time of ICI start (T1), after 3 weeks (T2) and at the time of radiological evaluation (T3). Molecular variables were associated with outcome endpoints: cfDNA quantification, its dynamic change (∆T2-T1), variant allele frequency (VAF) of the gene with the highest frequency detected at baseline with NGS (maxVAF) and its dynamic change (∆T2-T1).

Lenvatinib versus Sorafenib Second-Line Therapy in Patients with Hepatocellular Carcinoma Progressed to Atezolizumab plus Bevacizumab: A Retrospective Real-World Study.

Introduction: The most frequently used first-line treatment in patients with advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab. Upon progression after this treatment, the standard of care in many countries is sorafenib, due to the lack of reimbursement for other drugs. Several randomized trials are currently underway to clarify the best second-line therapy in patients with HCC.

Updated EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection - Update 1.

The standard of care for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a major part of the standard treatment, however, the predictive significance of most of the targets for treatment in systemic cancer are less well established in central nervous system (CNS) tumors . In 2023 the EANO Guideline Committee presented evidence based recommendations for rational testing of molecular targets for targeted treatments.

Endoscopic or combined management of post-surgical biliary leaks: a two-center recent experience.

Background And Aims: Post-surgical biliary leaks (PSBL) are one of the most prevalent and significant adverse events emerging after liver or biliary tract surgeries. Endoscopic retrograde cholangiopancreatography (ERCP) alone or combined with another approach (Rendez Vous) as treatment of PSBL obtains optimal outcomes due to the possibility of modifying the resistances in the biliary tree.

Methods: A retrospective double-center study was conducted in two tertiary centers.

Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4 T cell response.

Dendritic cells (DCs) are uniquely capable of transporting tumor antigens to tumor-draining lymph nodes (tdLNs) and interact with effector T cells in the tumor microenvironment (TME) itself, mediating both natural antitumor immunity and the response to checkpoint blockade immunotherapy. Using LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts)-based single-cell transcriptomics, we identified individual DCs capable of presenting antigen to CD4 T cells in both the tdLN and TME. Our findings revealed that DCs with similar hyperactivated transcriptional phenotypes interact with helper T cells both in tumors and in the tdLN and that checkpoint blockade drugs enhance these interactions.