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.

Immunotherapy in non-small-cell lung cancer: a bridge between research and clinical practice.

Lung cancer has been historically considered a poorly immunogenic disease because of the few evidence of immune responses in affected patients and the limited efficacy of immunomodulating strategies. Recent understanding of the molecular mechanisms leading to cancer immune evasion has allowed the development of a new class of drugs called immune checkpoint inhibitors, which reactivate host responses with outstanding clinical benefits in a portion of patients with non-small-cell lung cancer. In this review, we briefly summarize the basis of immunogenicity and immune escape of cancer, with specific focus on non-small-cell lung cancer, mechanisms underlying immune checkpoint inhibitors efficacy and the most updated results on potential biomarkers, with the final aim of defining current unmet needs of immunotherapy in clinical practice.

Acute Massive and Submassive Pulmonary Embolism: Preliminary Validation of Aspiration Mechanical Thrombectomy in Patients with Contraindications to Thrombolysis.

Purpose: The aim of this study is to assess the feasibility of aspiration mechanical thrombectomy in patients with massive and submassive pulmonary embolism (PE) and contraindications to thrombolysis.

Materials And Methods: Eighteen patients presenting massive (8/18) or submassive (10/18) PE were prospectively enrolled between October 2016 and November 2017. All the patients enrolled had contraindications to thrombolysis (haemorrhagic stroke n = 1, ischaemic stroke in the preceding 6 months n = 7, central nervous system damage or neoplasms n = 1, recent major trauma/surgery/head injury in the preceding 3 weeks n = 5, gastrointestinal bleeding within the last month n = 4).

Extracellular Vesicles: A New Prospective in Crosstalk between Microenvironment and Stem Cells in Hematological Malignancies.

The bone marrow (BM) microenvironment in hematological malignancies (HMs) comprises heterogeneous populations of neoplastic and nonneoplastic cells. Cancer stem cells (CSCs), neoplastic cells, hematopoietic stem cells (HSCs), and mesenchymal stromal/stem cells (MSCs) are all components of this microenvironment. CSCs are the HM initiators and are associated with neoplastic growth and drug resistance, while HSCs are able to reconstitute the entire hematopoietic system; finally, MSCs actively support hematopoiesis.

Comparative analysis of azacitidine and intensive chemotherapy as front-line treatment of elderly patients with acute myeloid leukemia.

The present observational study aimed to compare the efficacy of azacitidine (AZA) and intensive chemotherapy (IC) in elderly patients with untreated acute myeloid leukemia (AML), diagnosed according to WHO criteria. In the two groups, we evaluated complete remission (CR), overall survival (OS), and disease-free survival (DFS). The AZA group included 89 patients; median age was 73 years (range 61-80) and median white blood cell count (WBCc) 2.

Treatment Intensification With Autologous Stem Cell Transplantation and Lenalidomide Maintenance Improves Survival Outcomes of Patients With Newly Diagnosed Multiple Myeloma in Complete Response.

Background: High-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy.

Smenamide A Analogues. Synthesis and Biological Activity on Multiple Myeloma Cells.

Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16--analogue of smenamide A and eight simplified analogues in the 16- series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16--derivative is still active at nanomolar concentrations.

Association between ramucirumab-related hypertension and response to treatment in patients with metastatic gastric cancer.

Purpose: Hypertension (HTN) is frequently associated with the use of angiogenesis inhibitors targeting the vascular endothelial growth factor pathway, such as ramucirumab. The aim of this study was to retrospectively evaluate if occurrence of HTN is correlated with response to second line treatment with ramucirumab+paclitaxel for metastatic gastric cancer.

Methods: Treatment consisted of ramucirumab 8 mg/kg intravenously (iv) on days 1 and 15, plus paclitaxel 80 mg/m iv on days 1, 8, and 15 of a 28-day cycle.

Features of peripheral CD8CD57 lymphocytes in patients with autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) is an acquired condition characterized by the presence of autoantibodies recognizing erythrocyte-related antigens. Several components of the immune system are involved in disease pathogenesis. Among them, as for other autoimmune disorders, a role for specific CD8CD57 regulatory cells subset could be hypothesized.

Is there a role for immunotherapy in malignant pleural mesothelioma?

Malignant pleural mesothelioma (MPM) is a very aggressive malignancy, mainly caused by asbestos exposure. Patients with MPM have a poor prognosis that remained substantially unchanged in the last few years and limited effective therapeutic options with no recognized second or further-line therapy. In this context, also in view of the positive results observed in other tumor types, immunotherapy could play a relevant role.

Lenvatinib for the treatment of renal cell carcinoma.

Introduction: Renal cell carcinoma (RCC) accounts for 2-3% of all solid tumors. Expression of the receptor for the vascular endothelial growth factor (VEGF) is one of the most common features of RCC.

Areas Covered: Lenvatinib is a novel multi-kinase inhibitor that has been studied in several solid tumors.

Monoclonal Antibodies and Multiple Myeloma: All in All It's Just Another Brick in the Wall?

This commentary offers insight about the recent review by the European Medicines Agency on the approval of daratumumab for the treatment of adult patients with multiple myeloma.

Pathogenicity of In Vivo Generated Intestinal Th17 Lymphocytes is IFNγ Dependent.

Background And Aims: T helper 17 [Th17] cells are crucially involved in the immunopathogenesis of inflammatory bowel diseases in humans. Nevertheless, pharmacological blockade of interleukin 17A [IL17A], the Th17 signature cytokine, yielded negative results in patients with Crohn's disease [CD], and attempts to elucidate the determinants of Th17 cells' pathogenicity in the gut have so far proved unsuccessful. Here, we aimed to identify and functionally validate the pathogenic determinants of intestinal IL-17-producing T cells.

Correction: miR-451a is underexpressed and targets AKT/mTOR pathway in papillary thyroid carcinoma.

[This corrects the article DOI: 10.18632/oncotarget.7262.

Life for patients with myelofibrosis: the physical, emotional and financial impact, collected using narrative medicine-Results from the Italian 'Back to Life' project.

Purpose: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterised by an aggressive clinical course, with disabling symptoms and reduced survival. Patients experience a severely impaired quality of life and their families face the upheaval of daily routines and high disease-related financial costs. The aim of this study was to investigate the perceptions of Italian patients and their caregivers about living with MF and the burden of illness associated with MF.

MicroRNAs as New Biomarkers for Diagnosis and Prognosis, and as Potential Therapeutic Targets in Acute Myeloid Leukemia.

Acute myeloid leukemias (AML) are clonal disorders of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). miRNAs are small non-coding RNAs that regulate, at post-transcriptional level, translation and stability of mRNAs.

Is the fatigue an adverse event of the second generation of hormonal therapy? Data from a literature-based meta-analysis.

New hormonal therapies have enriched the therapeutic armamentarium for patients with castration-resistant prostate cancer (CRPC). Fatigue is one of the most common adverse events registered in phase III trials of these new drugs. The aim of this article is to perform a meta-analysis based on all available literature data focused on the risk rate (RR) of fatigue from new hormonal agent-based therapy in patients with CRPC.

Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma.

This multicentre, open-label phase 1/2 trial determined safety and efficacy of weekly carfilzomib plus cyclophosphamide-dexamethasone (wKCyd) in newly diagnosed multiple myeloma (NDMM) patients aged ⩾65 years or transplant ineligible. Patients received wKCyd for up to nine 28-day cycles, followed by maintenance with carfilzomib until progression/intolerance. The phase 1 portion used a 3+3 dose-escalation scheme to determine the maximum tolerated dose of weekly carfilzomib: 12 patients received wKCyd with carfilzomib doses of 45, 56 and 70 mg/m.

Italian real life experience with brentuximab vedotin: results of a large observational study on 234 relapsed/refractory Hodgkin's lymphoma.

A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context. 234 CD30+ HL patients were enrolled. Best response was observed after a median of 4 cycles in 140 patients (59.

Molecular characterization and prognostic significance of circulating tumor cells in patients with non-small cell lung cancer.

Circulating tumor cells (CTCs) are rare epithelial cells that can be found in the peripheral blood of cancer patients. A growing body of evidence indicates that CTCs may play a role in non-small cell lung cancer (NSCLC) for diagnosis, therapy monitoring and prognostic purposes. CTCs evaluation could be particularly relevant in this clinical setting, considering that physicians often have difficulty in obtaining an adequate tumor tissue and that patients are not always suitable to receive a re-biopsy.

Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells' vulnerability to DNA-damaging agents.

Genomic instability plays a pathological role in various malignancies, including acute myeloid leukemia (AML), and thus represents a potential therapeutic target. Recent studies demonstrate that SIRT6, a NAD-dependent nuclear deacetylase, functions as genome-guardian by preserving DNA integrity in different tumor cells. Here, we demonstrate that also CD34 blasts from AML patients show ongoing DNA damage and SIRT6 overexpression.

Targeting COPZ1 non-oncogene addiction counteracts the viability of thyroid tumor cells.

Thyroid carcinoma is generally associated with good prognosis, but no effective treatments are currently available for aggressive forms not cured by standard therapy. To find novel therapeutic targets for this tumor type, we had previously performed a siRNA-based functional screening to identify genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same extent for the viability of normal cells (non-oncogene addiction paradigm). Among those, we found the coatomer protein complex ζ1 (COPZ1) gene, which is involved in intracellular traffic, autophagy and lipid homeostasis.