Cancer
- CM-Path Molecular Diagnostics Forum—consensus statement on the development and implementation of molecular diagnostic tests in the United KingdomBritish Journal of Cancer, Published online: 02 October 2019; doi:10.1038/s41416-019-0588-1CM-Path Molecular Diagnostics Forum—consensus statement on the development and implementation of molecular diagnostic tests in the United Kingdom
The Journal of Physiology
Anthropology-News
- Brexit from BelowA Northern Ireland Catholic farming community’s perspectives on travel offer insight into resilience. “Brexit” refers to the upcoming withdrawal of the United Kingdom (UK) from the European Union (EU). Currently, it is scheduled for October 31, 2019, although it may be further delayed if British Prime Minister Boris Johnson is forced to request an extension to the Brexit deadline if there is no deal agreed by October 19; or cancelled, if a secon
Cancer Discovery current issue
- Single-Cell RNA Sequencing Reveals a Developmental Hierarchy in Langerhans Cell Histiocytosis [In the Spotlight]Summary:In this issue of Cancer Discovery, Halbritter and colleagues utilize single-cell RNA sequencing to dissect the cellular hierarchy in Langerhans cell histiocytosis. They identified a remarkably consistent composition of 14 cellular subsets across all patients with a range of clinical spectrums consistent with a shared developmental hierarchy driven by key transcriptional regulators. See related article by Halbritter et al., p. 1406.
- Splicing Factor-Mutant Leukemias Are Sensitive to PRMT Inhibitors [Leukemia]Splicing factor mutations increased protein arginine methyltransferase (PRMT) inhibitor sensitivity.
- Entrectinib OK'd for Cancers with NTRK Fusions, NSCLC [News in Brief]The FDA has approved entrectinib for patients with any solid tumor bearing NTRK fusions, making it the second TRK inhibitor to receive a tissue-agnostic approval; larotrectinib was the first. How the drugs compare to each other remains unknown. Entrectinib was also approved to treat metastatic non–small cell lung cancer with ROS1 rearrangements.
- A Mutation in Histone H2B Represents a New Class of Oncogenic Driver [Research Articles]By examination of the cancer genomics database, we identified a new set of mutations in core histones that frequently recur in cancer patient samples and are predicted to disrupt nucleosome stability. In support of this idea, we characterized a glutamate to lysine mutation of histone H2B at amino acid 76 (H2B-E76K), found particularly in bladder and head and neck cancers, that disrupts the interaction between H2B and H4. Although H2B-E76K forms d
- Targeting WEE1 in Pancreatic Cancer [News in Brief]According to results from a phase I/II trial, the investigational WEE1 inhibitor adavosertib combined with gemcitabine and radiation is well tolerated and may benefit patients with locally advanced pancreatic adenocarcinoma by increasing both systemic and local disease control.
- The Structure of CCR7 Reveals a Binding Pocket for Antagonists [Drug Discovery]A screen based on the structure of CCR7, associated with metastasis, revealed potential antagonists.
- Neoadjuvant Pembrolizumab Takes on TNBC [News in Brief]Pembrolizumab plus chemotherapy may be an effective neoadjuvant treatment for triple-negative breast cancer. In the phase III KEYNOTE-522 trial, patients treated with the PD-1 inhibitor in combination with chemotherapy prior to surgery were more likely to have a pathologic complete response than patients who received chemotherapy alone, regardless of PD-L1 levels.
- Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer [Research Articles]Small-cell lung cancer (SCLC) is an aggressive malignancy in which inhibitors of PARP have modest single-agent activity. We performed a phase I/II trial of combination olaparib tablets and temozolomide (OT) in patients with previously treated SCLC. We established a recommended phase II dose of olaparib 200 mg orally twice daily with temozolomide 75 mg/m2 daily, both on days 1 to 7 of a 21-day cycle, and expanded to a total of 50 patients. The con
- RNA Technologies Expand Tool Kit for Cancer Immunotherapy [News in Depth]Multiple companies are pursuing mRNA-based medicines that harness the body's protein-making machinery to transform lab-synthesized nucleotides into cancer-associated antigens, in the case of vaccines, or immune-stimulating molecules, in the case of therapeutics. Several candidates from BioNTech and Moderna have shown promise in early-stage testing.
- Resistance to ALK Inhibitors in Neuroblastoma Is Regulated by BORIS [Neuroblastoma]The transcription factor BORIS promotes resistance-associated chromatin regulatory interactions.
- Adoptive Transfer of HPV-Targeted T Cells Is Active in Epithelial Cancer [Clinical Trials]Adaptive transfer of engineered T cells promoted tumor regression and objective responses in epithelial cancer.
- Safety and Preliminary Evidence of Efficacy Shown for Rogaratinib [Clinical Trials]A phase I trial of the FGFR inhibitor rogaratinib showed safety and efficacy in advanced cancers.
- Off-Target Alterations Drive Resistance to TRK Inhibitors in Some Cancers [Drug Resistance]Some cancers that acquired TRK-inhibitor resistance had alterations affecting BRAF, KRAS, or MET.
- RAD51AP1 Promotes Maintenance of Telomere Length in ALT+ Cancer Cells [Telomeres]Cancer cells using alternative lengthening of telomeres (ALT) require RAD51AP for telomere maintenance.
- Deglycation of NRF2 by FN3K Promotes Oncogenesis and Drug Resistance [Glycation]Fructosamine-3-kinase (FN3K) activity promotes oncogenesis in models of liver and lung cancer.
- Tumor Microenvironment Dynamics in Clear-Cell Renal Cell Carcinoma [Mini Review]Renal cell carcinoma stands out as one of the most immune-infiltrated tumors in pan-cancer comparisons. Features of the tumor microenvironment heavily affect disease biology and may affect responses to systemic therapy. With evolving frontline options in the metastatic setting, several immune checkpoint blockade regimens have emerged as efficacious, and there is growing interest in characterizing features of tumor biology that can reproducibly pr
- CRISPR Screening in T Cells Identifies Potential Immunotherapy Targets [Immunotherapy]A CRISPR screen in CD8+ T cells revealed genes that modulate T-cell effector functions, including Dhx37.
- Epigenomics and Single-Cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis [Research Articles]Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a hybrid position between cancers and inflammatory diseases, which makes it an attractive model for studying cancer development. To explore the molecular mechanisms underlying the pathophysiology of LCH and its characteristic clinical heterogeneity, we investigated the transcriptomic and epigenomic diversity in primary LCH lesions. Using single-ce
- A Previously Unknown Mutation in RABL3 Is Linked to Hereditary PDAC [Pancreatic Cancer]A mutation in the little-studied gene RABL3 was found in a family with a history of PDAC.
- Enfortumab Vedotin Checks Urothelial Cancer [News in Brief]Treatment with enfortumab vedotin generated robust responses in patients with locally advanced or metastatic urothelial carcinoma. In a phase II trial of 125 patients who had previously received platinum-based chemotherapy and a PD-1 or PD-L1 checkpoint inhibitor, the overall response rate was 44%. Although nearly all patients experienced a treatment-related adverse event, most side effects were mild to moderate.
- Cancer-Linked SF3B1 Mutations Cause Faulty Splicing and SUGP1 Binding [Splicing]SF3B1 mutations, common in myelodysplastic syndromes, cause SUGP1-mediated splicing defects.
- People [News in Brief]Thomas J. Eichler, MD; Eric Van Cutsem, MD, PhD; and Angelo Di Leo, MD, are featured.
- High LMO2 Expression Confers Sensitivity to PARP Inhibition in DLBCL [Lymphoma]LMO2 expression correlated with increased response to olaparib and olaparib with R-CHOP.
- Immunotherapy Shows Promise in Pancreatic Cancer [News in Brief]A multiantigen-specific T-cell therapy that involves treating patients with their own nonengineered T cells cultured with peptides from cancer-associated antigens may be promising in pancreatic cancer: In a phase I trial, the therapy was safe and was associated with responses in several patients with advanced disease who were also receiving chemotherapy.
- OLIG2-Expressing Progenitors May Initiate Medulloblastoma Tumor Formation [Medulloblastoma]OLIG2 expression characterized progenitor cells in the SHH medulloblastoma subtype (SHH-MB).
- Gone Wildling: Building a Better Lab Mouse [News in Brief]By implanting wild female mice with common lab mouse embryos, researchers created a "wildling" model that combines natural microbiota with tractable genetics and, as a result, may improve the value of translational research.
- At Phase Ib, T-DM1 plus Neratinib Is Safe and Effective in Breast Cancer [Breast Cancer]T-DM1 plus neratinib was safe and showed preliminary efficacy in HER2-positive breast cancer.
- Exact Sciences Buys Genomic Health for $2.8 Billion [News in Brief]Cancer diagnostic test manufacturer Exact Sciences bought Genomic Health in a $2.8 billion deal. The sale is not likely to affect the companies' current products–Cologuard and Oncotype DX assays–but may promote development of new tests to detect other cancers.
- Temozolomide plus PARP Inhibition in Small-Cell Lung Cancer: Could Patient-Derived Xenografts Accelerate Discovery of Biomarker Candidates? [In the Spotlight]Summary:Effective options are limited for patients with small-cell lung cancer who develop progressive disease during or after etoposide plus platinum-based therapy. In this issue of Cancer Discovery, Farago and colleagues highlight the data for temozolomide plus olaparib in this patient population and demonstrate the potential to accelerate biomarker discovery through co-clinical trials utilizing patient-derived xenografts. See related article
- Fedratinib Becomes New Option in Myelofibrosis [News in Brief]The FDA recently approved fedratinib for myelofibrosis, making it just the second drug approved for the disease, as well as the second approved JAK inhibitor. The approval was based on the phase III JAKARTA trial, in which the drug significantly reduced symptoms compared with a placebo. However, the drug comes with a Boxed Warning for encephalopathy.
- Bringing Oncohistones into the Fold [In the Spotlight]Summary:Identification of cancer-associated mutations in core histone genes has proved challenging due to these genes' highly conserved nature and presence in large arrays. Recent analyses of cancer genomes, including one in this issue of Cancer Discovery, show that mutations in the histone fold can affect nucleosome stability, providing a novel mechanism by which oncohistones contribute to tumorigenesis. See related article by Bennett et al., p
- Sylvester Cancer Center Receives NCI Designation [News in Brief]The University of Miami's Sylvester Comprehensive Cancer Center recently became one of 71 NCI-Designated Cancer Centers nationwide. The distinction recognizes the center's research programs as well as its community outreach efforts to increase screening, detection, and treatment of cancer in underserved populations.
- Distinct Colorectal Cancer-Associated APC Mutations Dictate Response to Tankyrase Inhibition [Research Brief]The majority of colorectal cancers show hyperactivated WNT signaling due to inactivating mutations in the adenomatous polyposis coli (APC) tumor suppressor. Genetically restoring APC suppresses WNT and induces rapid and sustained tumor regression, implying that reengaging this endogenous tumor-suppressive mechanism may be an effective therapeutic strategy. Here, using new animal models, human cell lines, and ex vivo organoid cultures, we show tha
- Noted [News in Brief]A collection of recently published news items.
- Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment: The VIKTORY Umbrella Trial [Research Articles]The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overexpression, all negative, TSC2 deficient, or RICTOR amplification) to assign patients to one of the 10 associated clinical trials in second-l
- TMB Faces Validation Hurdles [News in Depth]As immune checkpoint inhibitors are approved for more cancers and indications, researchers continue to hunt for biomarkers that can predict which patients will respond to the therapies. One such biomarker, tumor mutation burden, has potential, but requires better standardization across labs and institutions, as well as stronger prospective clinical trial data, before it can be considered for routine clinical use.
- The Mechanism of Anti-PD-L1 Antibody Efficacy against PD-L1-Negative Tumors Identifies NK Cells Expressing PD-L1 as a Cytolytic Effector [Research Articles]Blockade of PD-L1 expression on tumor cells via anti–PD-L1 monoclonal antibody (mAb) has shown great promise for successful cancer treatment by overcoming T-cell exhaustion; however, the function of PD-L1 on natural killer (NK) cells and the effects of anti–PD-L1 mAb on PD-L1+ NK cells remain unknown. Moreover, patients with PD-L1– tumors can respond favorably to anti–PD-L1 mAb therapy for unclear reasons. Here, we show that some tumors can induc
- Tumor Microbiome Composition Influences Pancreatic Cancer Survival [Microbiome]Distinct tumor microbiomes are associated with long- and short-term survival in patients with PDAC.
- Altered Nuclear Export Signal Recognition as a Driver of Oncogenesis [Research Articles]Altered expression of XPO1, the main nuclear export receptor in eukaryotic cells, has been observed in cancer, and XPO1 has been a focus of anticancer drug development. However, mechanistic evidence for cancer-specific alterations in XPO1 function is lacking. Here, genomic analysis of 42,793 cancers identified recurrent and previously unrecognized mutational hotspots in XPO1. XPO1 mutations exhibited striking lineage specificity, with enrichment
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου