Current Status of Fibroblast Growth Factor Receptor-Targeted Therapies in Breast Cancer

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is an urgent need for better knowledge of the biology leading to the disease, which can lead to the design of increasingly accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC

Clinical outcomes and safety of patients treated with NAb-Paclitaxel plus Gemcitabine in metastatic pancreatic cancer:the NAPA study

BACKGROUND: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice.METHODS: From January 2015 to December 2018, patients with metastatic PDAC receiving first-line treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed.RESULTS: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95 % CI; 9-13) and the median progression free survival (PFS) was 6 months (95 % CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 haematological toxicity frequency was 22.61% for neutropenia, 5.22% for anaemia and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 nonhaematological events were reported. Dose reduction was necessary in 51.3 % of the patients.CONCLUSIONS: Our results confirm the efficacy and safety of a first line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.</p

Need for randomized clinical trials testing targeted therapies in malignant pleural mesothelioma

Malignant Pleural Mesothelioma (MPM) is a rare and aggressive tumour affecting the internal lining of the pleura. It is characterized by a poor prognosis and patients normally do not live longer than 12 months. The main cause of this disease is known to be asbestos, although there are some studies pointing at the involvement of Simian virus 40 in its pathogenesis. Other factors that may be involved in the pathogenesis include environmental exposure to erionite, fluoro-edenite and ionizing radiation as well as exposure to ceramic fibres [1,5]. The current standard treatment is the combination of cisplatin with pemetrexed [6,7]. However the average survival for this tumour still remains around 1 year. Hence there is an urgent need for a better understanding of the underlying biology of the disease to identify new actionable targets and improve patients\u2019 outcomes. In fact, no targeted therapies have been approved so far for the treatment of the disease. Using data collected from the literature on the very few randomized MPM clinical trials available, we performed a meta-analysis with the aim of investigating the efficacy of targeted therapies in MPM

Apatinib for the treatment of gastric cancer

Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2, has demonstrated encouraging anti-cancer activity in gastric cancer within both in vitro and in vivo models. AREAS COVERED: Apatinib's efficacy, tolerability and safety have been evaluated in one Phase II and one Phase III study in metastatic/advanced gastric cancer. In this review, we focus on the mechanism of action of apatinib, its pharmacokinetic profile and its clinical activity in the treatment of advanced/metastatic gastric cancer. Expert commentary: Unfortunately, as yet, there is no definitive biomarker data for apatinib in gastric cance

Subtotal versus total gastrectomy for T3 adenocarcinoma of the antrum

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Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts

Gemcitabine, oxaliplatin, and capecitabine (GEMOXEL) compared with gemcitabine alone in metastatic pancreatic cancer: a randomized phase II study

Background: Single-agent gemcitabine (GEM) has been considered for many years as the standard first-line treatment for advanced pancreatic cancer. However, recently, several studies reported encouraging activity and good tolerability for some combination regimens. Considering the apparently non-overlapping toxicity and the proved individual efficacy of GEM, oxaliplatin (l-OHP), and capecitabine (CAP), this randomized phase II study compared the activity and safety of the combination GEM, l-OHP, and CAP (GEMOXEL) versus GEM alone, in patients with metastatic pancreatic cancer. Materials and methods: The treatment in GEMOXEL arm consisted of GEM 1,000 mg/m2 as a 30-min intravenous infusion on days 1, 8, 15, 22, l-OHP 100 mg/m2 i.v. on day 2, and CAP 1,500 mg/m2/day in two divided doses on days 1-14, every 21 days (one cycle). In both treatment groups, GEM was administered weekly for seven consecutive weeks followed by 1-week rest for the first 8 weeks, and thereafter, GEM was continued on days 1, 8, 15, every 28 days. Chemotherapy was administered until disease progression or unacceptable toxicity. Results: Sixty-seven patients were enrolled in the study. Thirty-four were randomly assigned to GEMOXEL and 33 to GEM. At 4 months, disease control rate was 79.4 % with GEMOXEL versus 45.4 % with GEM (p = 0.004). The median progression-free survival was 6.8 months (95 % CI 5.3-7.3 months) in GEMOXEL arm and 3.7 months (95 % CI 2.9-4.7 months) in GEM arm (p < 0.001). The median OS was 11.9 months (95 % CI 10.6-12.9 months) in GEMOXEL arm and 7.1 months (95 % CI 5.5-9.1 months) in GEM arm (p < 0.001). Hematologic and non-hematologic toxicity was more severe with combination chemotherapy, yet still tolerable. No grade 4 adverse events were observed with either regimen. Conclusion: GEMOXEL regimen seemed to be safe and more efficient than the standard therapy with GEM alone in the treatment of metastatic pancreatic cancer

Anti-Coronavirus Vaccines: Past Investigations on SARS-CoV-1 and MERS-CoV, the Approved Vaccines from BioNTech/Pfizer, Moderna, Oxford/AstraZeneca and others under Development Against SARS-CoV-2 Infection

The aim of this review article is to summarize the knowledge available to date on prophylaxis achievements to fight against Coronavirus. This work will give an overview of what is reported in the most recent literature on vaccines (under investigation or already developed like BNT162b2, mRNA-1273, and ChAdOx1-S) effective against the most pathogenic Coronaviruses (SARS-CoV-1, MERS-CoV-1, and SARS-CoV-2), with of course particular attention paid to those under development or already in use to combat the current COVID-19 (COronaVIrus Disease 19) pandemic. Our main objective is to make a contribution to the comprehension, additionally at a molecular level, of what is currently ready for anti-SARS-CoV-2 prophylactic intervention, as well as to provide the reader with an overall picture of the most innovative approaches for the development of vaccines that could be of general utility in the fight against the most pathogenic Coronaviruses