Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
Mon Aug 31, 2020 10:00
Splicing alterations are common in diseases such as cancer, where mutations in splicing factor genes are frequently responsible for aberrant splicing. Here we present an alternative mechanism for splicing regulation in T-cell acute lymphoblastic leukemia (T-ALL) that involves posttranslational stabilization of the splicing machinery via deubiquitination. We demonstrate there are extensive exon skipping changes in disease, affecting proteasomal subunits, cell-cycle regulators, and the RNA machinery....
Tue Sep 01, 2020 10:05
A proliferative, chemoresistant cell type and another with metastatic potential were identified.
Tue Sep 01, 2020 10:05
Summary: The COVID-19 pandemic has caused widespread disruption of cancer clinical trials due to the restrictions on nonessential services and the reallocation of resources, and at the same time the urgent global effort toward discovering therapies that treat or prevent COVID-19 infection has led to shortening of traditional regulatory timelines. This experience should stimulate similar urgency in the way future cancer research is conducted.
Tue Sep 01, 2020 10:05
The secreted iron-binding protein lipocalin-2 enabled cancer cells to survive in the leptomeninges.
Tue Sep 01, 2020 10:05
Raymond DuBois, MD, PhD, and Joann Sweasy, PhD, are featured.
Tue Sep 01, 2020 10:05
Tumor progression upon treatment arises from preexisting resistant cancer cells and/or adaptation of persister cancer cells committing to an expansion phase. Here, we show that evasion from viral mimicry response allows the growth of taxane-resistant triple-negative breast cancer (TNBC). This is enabled by an epigenetic state adapted to taxane-induced metabolic stress, where DNA hypomethylation over loci enriched in transposable elements (TE) is compensated by large chromatin domains of H3K27me3...
Tue Sep 01, 2020 10:05
Blueprint Medicines entered into a strategic partnership with Roche to jointly develop and commercialize pralsetinib, a targeted agent for RET-driven malignancies. If pralsetinib is approved, Roche's vast commercial network and diagnostic abilities could help the drug compete against another RET inhibitor, Eli Lilly's selpercatinib, which was approved in May.
Tue Sep 01, 2020 10:05
CD30-directed CAR T cells were safe and produced a 62% overall response rate in Hodgkin lymphoma.
Tue Sep 01, 2020 10:05
A new liquid biopsy test can accurately detect aberrant cancer-associated methylation patterns from minute amounts of DNA shed into the bloodstream. Although prospective validation is still needed, two studies highlight the assay's potential to noninvasively classify brain and kidney tumors.
Tue Sep 01, 2020 10:05
Summary: In this issue, Deblois and colleagues show how taxane-resistant triple-negative breast cancer cells evade viral mimicry response as a result of metabolic alteration, DNA hypomethylation, and relocation of histone H3K27 trimethylation (H3K27me3). This adaptation confers a therapeutic vulnerability to the inhibition of the H3K27me3 methyltransferase EZH2 in resistant cells, leading to tumor growth inhibition by viral mimicry reactivation. See related article by Deblois et al., p. 1312....
Tue Sep 01, 2020 10:05
A recent study suggests that a method that identifies exposure to viral infections could allow earlier diagnosis of hepatocellular carcinoma (HCC). The method discriminated patients with HCC from at-risk and healthy people and determined that at-risk individuals developed HCC almost 9 years earlier than it could be detected with standard screening techniques.
Tue Sep 01, 2020 10:05
Older patients with melanoma (>50 years old) have poorer prognoses and response rates to targeted therapy compared with young patients (<50 years old), which can be driven, in part, by the aged microenvironment. Here, we show that aged dermal fibroblasts increase the secretion of neutral lipids, especially ceramides. When melanoma cells are exposed to the aged fibroblast lipid secretome, or cocultured with aged fibroblasts, they increase the uptake of lipids via the fatty acid transporter...
Tue Sep 01, 2020 10:05
Due to the COVID-19 pandemic, oncologists have had to balance patients' need for treatment with their risk of contracting the disease, sometimes leading them to adjust standard treatment and/or rethink its timing. These decisions have been largely informed by guidelines, research, and shared decision-making—and their complexity led one group to develop a tool that might help.
Tue Sep 01, 2020 10:05
A hallmark of metastasis is the adaptation of tumor cells to new environments. Metabolic constraints imposed by the serine and glycine–limited brain environment restrict metastatic tumor growth. How brain metastases overcome these growth-prohibitive conditions is poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine synthesis, is a major determinant of brain metastasis in multiple human cancer types...
Tue Sep 01, 2020 10:05
Vor Biopharma secured $110 million in July to move its CD33-inactivated cell therapy into clinical testing. The company's hope is that patients with high-risk acute myeloid leukemia who receive transplants of the gene-edited stem cells will then better tolerate therapies designed to destroy cells expressing CD33, an antigen found in abundance on leukemic blasts.
Tue Sep 01, 2020 10:05
The U.S. Preventive Services Task Force recently proposed guidelines that would expand the criteria for lung cancer screening by reducing the requirements for age and smoking history. If finalized, the recommendations may address existing racial disparities by increasing screening eligibility among African Americans.
Tue Sep 01, 2020 10:05
Immune-checkpoint blockade (ICB) changed immune-cell populations and gene expression in the colon.
Tue Sep 01, 2020 10:05
The ability of mitochondrial complex III to oxidize ubiquinol was essential to tumor growth in vivo.
Tue Sep 01, 2020 10:05
Summary: Alicea and colleagues demonstrate that aged fibroblasts secrete lipids into the tumor microenvironment, allowing for nutrient exchange with melanoma cells. This supportive function of fibroblasts results in increased resistance to BRAF/MEKi therapy in the context of an aged microenvironment, providing crucial mechanistic insight into age-related drug resistance. See related article by Alicea et al., p. 1282.
Tue Sep 01, 2020 10:05
The ATR inhibitor berzosertib produced responses with or without the DNA-damaging agent carboplatin.
Tue Sep 01, 2020 10:05
Summary: Yu and colleagues combined computational and experimental techniques to identify a new post-transcriptional regulator of metastatic potential in colon cancer. This study reveals that the RNA-binding protein RBMS1 is a positive regulator of mRNA stability for multiple genes, including the tumor suppressor AKAP12 and a WNT pathway interacting protein, SDCBP, and its loss is a common event associated with poor prognosis. See related article by Yu et al., p. 1410.
Tue Sep 01, 2020 10:05
The TKI avapritinib showed preliminary evidence of efficacy in gastrointestinal stromal tumors.
Tue Sep 01, 2020 10:05
Diffuse large B-cell lymphoma (DLBCL) represents a grouping of clinically and biologically heterogeneous tumors. Application of advanced molecular technology has significantly expanded our knowledge of DLBCL pathobiology, allowing identification of subgroups with common, potentially targetable, biological themes. Here, we review the recent molecular analyses that could provide a paradigm shift to a new taxonomy, foundational to the rational transition to precision medicine. We discuss how classification...
Tue Sep 01, 2020 10:05
Cusatuzumab synergized with a hypomethylating agent in older patients with acute myeloid leukemia.
Tue Sep 01, 2020 10:05
The molecular mechanisms leading to resistance to PD-1 blockade are largely unknown. Here, we characterize tumor biopsies from a patient with melanoma who displayed heterogeneous responses to anti–PD-1 therapy. We observe that a resistant tumor exhibited a loss-of-function mutation in the tumor suppressor gene FBXW7, whereas a sensitive tumor from the same patient did not. Consistent with a functional role in immunotherapy response, inactivation of Fbxw7 in murine tumor cell lines caused resistance...
Tue Sep 01, 2020 10:05
A Tbl1xr1 loss-of-function mutation promoted memory B-cell fate and an aggressive lymphoma subtype.
Tue Sep 01, 2020 10:05
A subset of cancer-associated fibroblasts (FAP+/CAF-S1) mediates immunosuppression in breast cancers, but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 19,000 single CAF-S1 fibroblasts from breast cancer. We validate the five most abundant clusters by flow cytometry and in silico analyses in other cancer types, highlighting their relevance. Myofibroblasts from clusters 0 and 3, characterized by extracellular...
Tue Sep 01, 2020 10:05
An antibody blocking GRFAL–RET binding blunted GDF15-induced cachexia, preventing weight loss.
Tue Sep 01, 2020 10:05
Genetic inactivation of PTEN is common in prostate cancer and correlates with poorer prognosis. We previously identified CHD1 as an essential gene in PTEN-deficient cancer cells. Here, we sought definitive in vivo genetic evidence for, and mechanistic understanding of, the essential role of CHD1 in PTEN-deficient prostate cancer. In Pten and Pten/Smad4 genetically engineered mouse models, prostate-specific deletion of Chd1 resulted in markedly delayed tumor progression and prolonged survival....
Tue Sep 01, 2020 10:05
Coactivation of STAT5 and ERK suppressed transformation in B-cell acute lymphoblastic leukemia.
Tue Sep 01, 2020 10:05
Identifying master regulators that drive pathologic gene expression is a key challenge in precision oncology. Here, we have developed an analytic framework, named PRADA, that identifies oncogenic RNA-binding proteins through the systematic detection of coordinated changes in their target regulons. Application of this approach to data collected from clinical samples, patient-derived xenografts, and cell line models of colon cancer metastasis revealed the RNA-binding protein RBMS1 as a suppressor...
Tue Sep 01, 2020 10:05
Abstract The 2019 novel coronavirus (COVID‐19) global pandemic has shifted how many patients receive outpatient care. Telehealth and remote monitoring have become more prevalent, and measurements taken in a patient’s home using biometric monitoring technologies (BioMeTs) offer convenient opportunities to collect vital sign data. Healthcare providers may lack prior experience using BioMeTs in remote patient care, and therefore, may be unfamiliar with the many versions of BioMeTs, novel data collection...
Mon Aug 31, 2020 21:59
Purpose: Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had broad success as monotherapies, we hypothesized that targeted vaccination against an oncogenic driver in combination with ICB could direct and enable antitumor immunity in advanced cancers. Experimental Design: Our models of HER2+ breast cancer exhibit molecular signatures...
Tue Sep 01, 2020 10:05
Purpose: BRAFV600E mutations portend poor prognosis in metastatic colorectal cancer (mCRC); however, the true prevalence and prognosis are unknown, as unwell patients may not undergo BRAF sequencing. Experimental Design: We reviewed a population-based cohort of 1,898 patients with colorectal cancer that underwent reflexive IHC mismatch repair (MMR) and BRAFV600E testing. Outcomes among IHC-detected BRAFV600E mCRC (BRAFIHC) were compared with patients with next-generation sequencing (NGS)–identified...
Tue Sep 01, 2020 10:05
The cancer mutanome has been associated with disease prognosis as well as response to interventional immunotherapy and provides a substrate for development of personalized vaccines targeting tumor neoepitopes. Recent findings suggest that neoantigen-based vaccines may represent general interventional approaches for patients with solid cancers, regardless of their inherent mutational burden. See related article by Fang et al., p. 4511
Tue Sep 01, 2020 10:05
Purpose: Because BRCA1 is a high-risk breast/ovarian cancer susceptibility gene, BRCA1 sequence variants of uncertain clinical significance (VUS) complicate genetic counseling. As most VUS are rare, reliable classification based on clinical and genetic data is often impossible. However, all pathogenic BRCA1 variants analyzed result in defective homologous recombination DNA repair (HRR). Thus, BRCA1 VUS may be categorized based on their functional impact on this pathway. Experimental Design:...
Tue Sep 01, 2020 10:05
The modeled Ca125 ELIMination rate constant K (KELIM) can be used as a measure of chemotherapy sensitivity in women with newly diagnosed advanced epithelial ovarian cancer who are being treated with neoadjuvant chemotherapy. This marker may aid in decision-making regarding surgical resection and alternate systemic treatments in this cohort. See related article by You et al., p. 4625
Tue Sep 01, 2020 10:05
Purpose: The purpose of this study was to evaluate the rational combination of TORC1/2 inhibitor TAK-228 and Aurora A kinase inhibitor alisertib in preclinical models of triple-negative breast cancer (TNBC) and to conduct a phase I dose escalation trial in patients with advanced solid tumors. Experimental Design: TNBC cell lines and patient-derived xenograft (PDX) models were treated with alisertib, TAK-228, or the combination and evaluated for changes in proliferation, cell cycle, mTOR...
Tue Sep 01, 2020 10:05
Although the last two decades have seen a broad improvement in overall survival, colorectal cancer is still the second leading cause of cancer deaths worldwide. Patient populations continue to face poor disease prognoses due to the challenges of early detection and the molecular subtypes driving their colorectal cancer. Consequently, many patients present with metastatic colorectal cancer, which often limits options and shifts treatment focus away from curative interventions. BRAFV600E mutations...
Tue Sep 01, 2020 10:05
The introduction and the unexpected efficacy of checkpoint inhibitors (CPI) and more recently of chimeric antigen receptor T cells (CAR T-cells) in the treatment of malignant diseases boosted the efforts in the development and clinical application of immunotherapeutic approaches. However, the definition of predictive factors associated with clinical responses as well as the identification of underlying mechanisms that promote the therapeutic efficacy remain to be determined. Starting from the first...
Tue Sep 01, 2020 10:05
Purpose: Targeted therapies for cancer have accelerated the need for functional imaging strategies that inform therapeutic efficacy. This study assesses the potential of functional genetic screening to integrate therapeutic target identification with imaging probe selection through a proof-of-principle characterization of a therapy–probe pair using dynamic nuclear polarization (DNP)-enhanced magnetic resonance spectroscopic imaging (MRSI). Experimental Design: CRISPR-negative selection screens...
Tue Sep 01, 2020 10:05
Frequently, the results generated when testing novel antitumor immunotherapies in vitro do not correlate with data collected in in vivo models and/or in clinical settings. It is our hypothesis that this discrepancy is caused by the use of in vitro conditions, such as normoxia, a two-dimensional surface, optimal growth media, and lack of cell complexity and heterogeneity. These conditions do not accurately reflect the tumor microenvironment (TME) that the tested immunotherapeutic strategies experience...
Tue Sep 01, 2020 10:05
Purpose: The purpose of this study was to measure genomic changes that emerge with enzalutamide treatment using analyses of whole-genome sequencing and RNA sequencing. Experimental Design: One hundred and one tumors from men with metastatic castration-resistant prostate cancer (mCRPC) who had not been treated with enzalutamide (n = 64) or who had enzalutamide-resistant mCRPC (n = 37) underwent whole genome sequencing. Ninety-nine of these tumors also underwent RNA sequencing. We analyzed...
Tue Sep 01, 2020 10:05
Purpose: Combination immunotherapy with anti–CTLA-4 and anti–PD-1 blockade has demonstrated significant clinical activity across several tumor types. Neuroendocrine tumors (NET) are a heterogeneous group of rare tumors with limited treatment options. CA209-538 is a clinical trial of combination immunotherapy with ipilimumab and nivolumab in rare cancers, including advanced NETs. Patients and Methods: CA209-538 is a prospective multicenter clinical trial in patients with advanced rare cancers....
Tue Sep 01, 2020 10:05
Purpose: African American (AFR) men have the highest mortality rate from prostate cancer (PCa) compared with men of other racial/ancestral groups. Differences in the spectrum of somatic genome alterations in tumors between AFR men and other populations have not been well-characterized due to a lack of inclusion of significant numbers in genomic studies. Experimental Design: To identify genomic alterations associated with race, we compared the frequencies of somatic alterations in PCa obtained...
Tue Sep 01, 2020 10:05
Purpose: To evaluate the relationship between exposure of apalutamide and its active metabolite, N-desmethyl-apalutamide, and selected clinical efficacy and safety parameters in men with high-risk nonmetastatic castration-resistant prostate cancer. Patients and Methods: An exploratory exposure–response analysis was undertaken using data from the 1,207 patients (806 apalutamide and 401 placebo) enrolled in the SPARTAN study, including those who had undergone dose reductions and dose interruptions....
Tue Sep 01, 2020 10:05
Purpose: T-cell immunoreceptor with Ig and ITIM domain (TIGIT) blockade could represent an alternative therapeutic option to release the immune response in patients with multiple myeloma. Here we analyzed the expression of TIGIT and its ligands poliovirus receptor (PVR) and nectin-2 in the bone marrow (BM) of patients with monoclonal gammopathies and the efficacy of TIGIT blockade activating antimyeloma immunity. Experimental Design: Expression levels of TIGIT and its ligands were characterized...
Tue Sep 01, 2020 10:05
Purpose: We sought to improve upon frontline bendamustine/rituximab (BR) induction therapy followed by rituximab maintenance in untreated high-risk follicular lymphoma (FL). Patients and Methods: Patients were randomized to BR induction followed by 2-year rituximab maintenance (BR-R), BR with bortezomib and rituximab maintenance (BVR-R), or BR followed by lenalidomide (1 year) with rituximab maintenance (BR-LR). Dual primary objectives were complete remission (CR) rate and 1-year disease-free...
Tue Sep 01, 2020 10:05
Purpose: Tumor heterogeneity and burden, which impact treatment outcome in prostate cancer, are rarely evaluated using next-generation imaging. Experimental Design: The trial prospectively included 37 patients who had an early PSA progression (≤2 ng/mL) during castration and high-risk (PSA doubling time ≤10 months) nonmetastatic disease by conventional imaging. All patients underwent both 68Ga-PSMA and 18F-FDG PET/CT. Lesions were classified into PSMA+FDG± lesions and PSMA-FDG+ lesions....
Tue Sep 01, 2020 10:05
Purpose: Preclinical studies show that antiangiogenic therapy exacerbates tumor glycolysis and activates liver kinase B1/AMP kinase (AMPK), a pathway involved in the regulation of tumor metabolism. We investigated whether certain metabolism-related in situ biomarkers could predict benefit to regorafenib in the phase II randomized REGOMA trial. Patients and Methods: IHC and digital pathology analysis were used to investigate the expression in glioblastoma (GBM) sections of monocarboxylate...
Tue Sep 01, 2020 10:05
Purpose: The two most common molecular subtypes of endometrial cancers, mismatch repair deficient (MMRd) and p53 wild-type (p53wt) comprise the majority of endometrial cancers and have intermediate prognoses where additional risk stratification biomarkers are needed. Isoform switching of FGFR2 from FGFR2b to FGFR2c (normally expressed in mesenchymal cells), has been reported in other solid carcinomas. The objective of this study was to investigate the role of FGFR2c in risk stratification of endometrial...
Tue Sep 01, 2020 10:05
Purpose: After 10 years of clinical practice and research studies, there are still no validated prognostic or predictive factors of response to sorafenib for hepatocellular carcinoma (HCC). On the basis of the results of our two retrospective studies, we designed the multicenter INNOVATE study with the aim to validate the role of nitric oxide synthase 3 (NOS3) and ANGPT2 polymorphisms in patients with HCC treated with sorafenib [NCT02786342]. Patients and Methods: This prospective multicenter...
Tue Sep 01, 2020 10:05
Purpose: Various biomarkers have been proposed for sunitinib therapy in gastrointestinal stromal tumor (GIST). However, the lack of "real-life" comparative studies hampers the selection of the most appropriate one. We, therefore, set up a pharmacometric simulation framework to compare each proposed biomarker. Experimental Design: Models describing relations between sunitinib exposure, adverse events (hand–foot syndrome, fatigue, hypertension, and neutropenia), soluble VEGFR (sVEGFR)-3, and...
Tue Sep 01, 2020 10:05
Purpose: Natural killer (NK) cells exert antibody-dependent cell cytotoxicity (ADCC). We infused expanded, activated autologous NK cells to potentiate trastuzumab-mediated ADCC in patients with HER2-positive malignancies. Patients and Methods: In a phase I trial, patients with treatment-refractory HER2-positive solid tumors received trastuzumab, with or without bevacizumab, and autologous NK cells expanded by 10-day coculture with K562-mb15-41BBL cells. Primary objectives included safety...
Tue Sep 01, 2020 10:05
Genome Instability Profiles Predict Disease Outcome in a Cohort of 4,003 Patients with Breast Cancer
Purpose: The choice of therapy for patients with breast cancer is often based on clinicopathologic parameters, hormone receptor status, and HER2 amplification. To improve individual prognostication and tailored treatment decisions, we combined clinicopathologic prognostic data with genome instabilty profiles established by quantitative measurements of the DNA content. Experimental Design: We retrospectively assessed clinical data of 4,003 patients with breast cancer with a minimum postoperative...
Tue Sep 01, 2020 10:05
Purpose: DNA mismatch repair (MMR) deficiency is a hallmark of Lynch syndrome, the most common inherited cancer syndrome. MMR-deficient cancer cells accumulate numerous insertion/deletion mutations at microsatellites. Mutations of coding microsatellites (cMS) lead to the generation of immunogenic frameshift peptide (FSP) neoantigens. As the evolution of MMR-deficient cancers is triggered by mutations inactivating defined cMS-containing tumor suppressor genes, distinct FSP neoantigens are shared...
Tue Sep 01, 2020 10:05
Purpose: In patients with ovarian cancer receiving neoadjuvant chemotherapy, the first-line treatment success will depend on both the tumor-primary chemosensitivity and the completeness of interval debulking surgery (IDS). The modeled CA-125 ELIMination rate constant K (KELIM), calculated with the CA-125 longitudinal kinetics during the first 100 chemotherapy days, is a validated early marker of tumor chemosensitivity. The objective was to investigate the role of the chemosensitivity relative to...
Tue Sep 01, 2020 10:05
Purpose: Because of their high tumor specificity and immunogenicity, neoantigens have been considered as ultimate targets for cancer immunotherapy. Neoantigen-based vaccines have demonstrated promising efficacy for several cancer types. To further investigate the antitumor potentials for other types of solid tumors, we designed a peptide-based neoantigen vaccine, iNeo-Vac-P01, and conducted a single-arm, open-labeled, investigator-initiated clinical trial (NCT03662815). Patients and Methods:...
Tue Sep 01, 2020 10:05
Purpose: To quantitatively predict the impact of cardiopulmonary dose on overall survival (OS) after radiotherapy for locally advanced non–small cell lung cancer. Experimental Design: We used the NRG Oncology/RTOG 0617 dataset. The model building procedure was preregistered on a public website. Patients were split between a training and a set-aside validation subset (N = 306/131). The 191 candidate variables covered disease, patient, treatment, and dose-volume characteristics from multiple...
Tue Sep 01, 2020 10:05
Purpose: Patients with relapsed/refractory primary mediastinal B-cell lymphoma (rrPMBCL) represent a particularly challenging population to treat, with few life-saving treatment options in the context of a dismal prognosis. Patients and Methods: In this open-label, single-arm, phase II study, the safety and efficacy of combined regimen of chemotherapy consisting of gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) plus anti-PD-1 antibody camrelizumab was assessed in rrPMBCL....
Tue Sep 01, 2020 10:05
Purpose: Pancreatic cancer is one of the most lethal solid tumors, mainly because of its intrinsic chemoresistance. We identified TAK1 as a central hub sustaining this resistance. Nanoliposomal irinotecan (nal-IRI) is a novel treatment for metastatic gemcitabine-refractory pancreatic cancer. We endeavored to identify circulating markers for TAK1 activation predicting chemoresistance in this setting. Experimental Design: In vivo activity of nal-IRI was validated in an orthotopic nude murine...
Tue Sep 01, 2020 10:05
Purpose: The study goal was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti–C-C chemokine receptor 4 (anti-CCR4) mAb targeting effector regulatory T cells (eTreg), in combination with mAb checkpoint inhibitors durvalumab or tremelimumab. Patients and Methods: This was a multicenter, phase I, dose escalation study, followed by disease-specific cohort expansion (NCT02301130). Mogamulizumab dose escalation proceeded with concurrent dose escalation...
Tue Sep 01, 2020 10:05
Purpose: Invasive lobular carcinoma (ILC) accounts for approximately 5%–15% of all invasive breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on patients with invasive ductal carcinoma (IDC) or without distinction between the subtypes. Here, we investigate the prognostic value of EndoPredict (EPclin) in a large cohort of ILCs pooled from three phase III randomized trials (ABCSG-6, ABCSG-8, TransATAC). Experimental Design:...
Tue Sep 01, 2020 10:05
Purpose: This phase II study (NCT03469557) assessed safety/tolerability and antitumor activity of first-line tislelizumab, a monoclonal antibody against programmed cell death-1, plus chemotherapy in patients with locally advanced/metastatic esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Patients and Methods: Patients with ESCC received tislelizumab [200 mg i.v. every 3 weeks (Q3W)] plus cisplatin (80 mg/m² i.v. Q3W for ≤6 cycles) and...
Tue Sep 01, 2020 10:05
Purpose: Anti-programmed cell death protein 1 (PD-1) therapy has demonstrated inconsistent therapeutic results in patients with glioblastoma (GBM) including those with profound impairments in CD8 T-cell effector responses. Experimental Design: We ablated the CD8α gene in BL6 mice and intercrossed them with Ntv-a mice to determine how CD8 T cells affect malignant progression in forming endogenous gliomas. Tumor-bearing mice were treated with PD-1 to determine the efficacy of this treatment...
Tue Sep 01, 2020 10:05
Purpose:Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo–activated NK cells...
Tue Sep 01, 2020 18:01
Background and Aims: Chromosomal instability is a hallmark of cancer that results in broad and focal copy number alterations (CNAs), two events associated with distinct molecular, immunological and clinical features. In hepatocellular carcinoma (HCC) the CNAs role has not been thoroughly assessed. Thus, we dissected the impact of CNA burdens on HCC molecular and immune features. Methods: We analyzed SNP-array data from 452 paired tumor/adjacent resected HCCs and 25 dysplastic nodules. For each sample,...
Tue Sep 01, 2020 16:04
Purpose: Desmoid-type fibromatosis (DF) are locally aggressive neoplasms, with a need for effective systemic treatment in case of progression, in order to avoid the short- and long-term complications of local treatments. Experimental design: We retrospectively analyzed the outcomes of adult patients with DF treated with oral vinorelbine (90 mg once weekly) at Gustave Roussy Cancer Institute. Only patients with documented progressive disease (PD) according to RECIST v1.1 over 3 months (±2 weeks) before...
Tue Sep 01, 2020 16:04
Purpose: The cytokine milieu in pancreatic ductal adenocarcinoma (PDAC) promotes tumor progression and immune suppression, contributing to the dismal prognosis of patients with PDAC. The roles of many of these cytokines, however, have not been thoroughly investigated in PDAC. Experimental Design: PDAC microarray and TCGA datasets were analyzed to identify cytokines and cognate receptors overexpressed in PDAC and associated with survival. Pathway and CIBERSORT analyses were used to elucidate potential...
Tue Sep 01, 2020 16:04
Purpose: Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognoses and suboptimal outcomes with targeted therapy. This post hoc analysis of the phase III CheckMate 214 trial analyzed the efficacy of nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in patients with sRCC. Patients and Methods: Patients with sRCC were identified via independent central pathology review of archival tumor tissue or histological classification per local pathology report....
Tue Sep 01, 2020 16:04
Opinion statement The diagnosis of round cell sarcomas has changed rapidly over the last decade, causing much diagnostic confusion for pathologists and oncologists. The advances in diagnosis are largely due to the advent of next-generation sequencing techniques, which allowed the recognition of novel gene fusions in round cell sarcomas. The new 5th edition of the WHO Classification of Tumors of Soft Tissue and Bone recognizes four subgroups of undifferentiated round cell sarcomas:...
Tue Sep 01, 2020 03:00
Opinion statement Liquid biopsy using blood components to assess circulating tumor DNA (ctDNA) is rapidly becoming a new standard-of-care technology in many tumor types, including breast cancer, due to the potential to provide predictive and prognostic information. The minimally invasive and repeatable nature of plasma based mutational testing is appealing for patients and facilitates enhanced disease monitoring. It is important for the clinician to understand the benefits and...
Tue Sep 01, 2020 03:00
Future Oncology, Ahead of Print.
Tue Sep 01, 2020 14:49
Future Oncology, Ahead of Print.
Tue Sep 01, 2020 12:55
Future Oncology, Ahead of Print.
Tue Sep 01, 2020 12:52
Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. The communication between tumor-derived exosomes and macrophages has a critical role in facilitating...
Mon Aug 31, 2020 03:00
Overexpression of eukaryotic translation initiation factor 3H (EIF3H) predicts cancer progression and poor prognosis, but the mechanism underlying EIF3H as an oncogene remains unclear in esophageal squamous ce...
Mon Aug 31, 2020 03:00
Inhibition of p38 MAPK signalling leads to glioblastoma multiform (GBM) tumourigenesis. Nevertheless, the molecular mechanism that induces p38 MAPK signalling pathway silencing during GBM genesis has yet to be...
Mon Aug 31, 2020 03:00
Publication date: September–October 2020Source: Practical Radiation Oncology, Volume 10, Issue 5Author(s): Bhishamjit S. Chera, Louis Potters, Lawrence B. Marks
Tue Sep 01, 2020 23:06
Publication date: September–October 2020Source: Practical Radiation Oncology, Volume 10, Issue 5Author(s): Wesley J. Talcott, Holly Lincoln, Jacqueline R. Kelly, Lauren Tressel, Lynn D. Wilson, Roy H. Decker, Eric Ford, Pehr E. Hartvigson, Todd Pawlicki, Suzanne B. Evans
Tue Sep 01, 2020 23:06
Publication date: September–October 2020Source: Practical Radiation Oncology, Volume 10, Issue 5Author(s): T.J. FitzGerald
Tue Sep 01, 2020 23:06
Publication date: September–October 2020Source: Practical Radiation Oncology, Volume 10, Issue 5Author(s):
Tue Sep 01, 2020 23:06
Publication date: September–October 2020Source: Practical Radiation Oncology, Volume 10, Issue 5Author(s):
Tue Sep 01, 2020 23:06
Publication date: September–October 2020Source: Practical Radiation Oncology, Volume 10, Issue 5Author(s):
Tue Sep 01, 2020 23:06
The goal of this study was to assess small bowel motion and explore the feasibility of using peritoneal space (PS) to replace bowel loops (BL) via the dose constraint method to spare the small bowel during int...
Tue Sep 01, 2020 03:00
Trypanosome U-insertion/deletion RNA editing in mitochondrial mRNAs involves guide RNAs (gRNAs) and the auxiliary RNA Editing Substrate binding Complex (RESC) and RNA Editing Helicase 2 Complex (REH2C). RESC and REH2C stably co-purify with editing mRNAs but the functional interplay between these complexes remains unclear. Most steady-state mRNAs are partially edited and include mis-edited ‘junction’ regions that match neither pre-mRNA nor fully-edited transcripts. Editing specificity is central to...
Tue Sep 01, 2020 20:47
Abstract Purpose The purpose of the reported study was to investigate the value of cone-beam computed tomography (CBCT)-based radiomics for risk stratification and prediction of biochemical relapse in prostate cancer. Methods The study population consisted of 31 prostate cancer patients. Radiomics features were extracted from weekly CBCT scans performed...
Tue Sep 01, 2020 03:00
Publication date: October 2020Source: Surgical Oncology Clinics of North America, Volume 29, Issue 4Author(s): Jenalee N. Coster, Shawn S. Groth
Tue Sep 01, 2020 14:15
Publication date: October 2020Source: Surgical Oncology Clinics of North America, Volume 29, Issue 4Author(s):
Tue Sep 01, 2020 14:15
Publication date: October 2020Source: Surgical Oncology Clinics of North America, Volume 29, Issue 4Author(s):
Tue Sep 01, 2020 14:15
Publication date: October 2020Source: Surgical Oncology Clinics of North America, Volume 29, Issue 4Author(s):
Tue Sep 01, 2020 14:15
Publication date: October 2020Source: Surgical Oncology Clinics of North America, Volume 29, Issue 4Author(s):
Tue Sep 01, 2020 14:15
Publication date: October 2020Source: Surgical Oncology Clinics of North America, Volume 29, Issue 4Author(s):
Tue Sep 01, 2020 14:15
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