Purpose:Enhanced lipogenesis and mitochondrial function are two critical metabolic characteristics in melanoma, but their crosstalk involved in tumor biology and targeted therapy remains unknown. ATP-citrate lyase (ACLY) is a crucial lipogenic enzyme that is greatly implicated in tumor development, but its role in mitochondrial function and melanoma pathogenesis has not been elucidated. Experimental Design:In vitro and in vivo functional experiments were performed to determine the effect of ACLY...
Mon Jun 01, 2020 10:06
Chimeric antigen receptor (CAR) T-cell therapy has been acclaimed as a revolution in cancer treatment following the impressive results in hematologic malignancies. Unfortunately, in patients with solid tumors, objectives responses to CAR T cells are still anecdotal, and important issues are driven by on-target but off-tumor activity of CAR T cells and by the extremely complex biology of solid tumors. Here, we will review the recent attempts to challenge the therapeutic impediments to CAR T-cell therapy...
Mon Jun 01, 2020 10:06
Matched pre-/posttreatment tissue biopsies from patients with EGFR-mutant non–small cell lung cancer demonstrate that histologic transformations, including both small-cell carcinoma and squamous transformation, are unexpectedly common among patients progressing on first-line osimertinib. The study highlights the key role of tissue testing and underscores the need for innovative therapeutic approaches to prevent, rather than treat, resistance. See related article by Schoenfeld et al., p. 2654
Mon Jun 01, 2020 10:06
PARP inhibitors (PARPi) are promising in BRCA2-altered prostate cancer. Data were presented on PARPi efficacy in prostate cancers with alterations in other DNA damage repair genes which suggest low response rates in ATM-, CHEK2-, CDK12-altered tumors and promising results in PALB2-, RAD51B-, FANCA-, and BRIP1-altered tumors. See related article by Abida et al., p. 2487
Mon Jun 01, 2020 10:06
ABSTRACT Background Atopic dermatitis (AD) patients have a barrier disorder in association with Th2 dominant skin inflammation. Galectin‐7 (Gal‐7), a soluble unglycosylated lectin, is highly expressed in the stratum corneum of AD patients. However, the biological significance of increased Gal‐7 expression in AD skin lesions remains unclear. Objective We aimed to investigate the production mechanism and functional role of Gal‐7 in AD patients and IL‐4/IL‐13‐stimulated epidermal keratinocytes....
Sun May 31, 2020 19:49
Abstract The UK has high allergy prevalence rates, with 30‐40% of the population affected by allergy. Hospital admissions for anaphylaxis, its most severe manifestation, have increased 7‐fold since 1990 (1). It has long been thought by many that most patients attending hospital as an emergency with anaphylaxis are not referred for specialist evaluation to determine its cause ( 2).
Sun May 31, 2020 14:04
Abstract Protein phosphatase 1 catalytic subunit beta (PPP1CB ) is a disease‐causing gene of Noonan‐like syndrome, which acts via the RAS/MAPK pathway. To date, only 17 patients diagnosed with PPP1CB ‐related Noonan‐like syndrome have been reported around the world, with few reports in Asia. Twelve reported patients are of short stature and only one patient was treated with growth hormone (GH); however, follow‐up data is lacking. To the best of our knowledge, this is the first reported patient with...
Mon Jun 01, 2020 11:08
Abstract We present the case of a male who shortly after birth developed acute respiratory distress due to bilateral choanal atresia, following which he was found to have rectal stenosis. Genetic testing for CHARGE syndrome was negative, but whole genome sequencing identified heterozygosity for a pathogenic missense variant in TP63 (c.727C > T, p.(Arg243Trp). He also has partial cutaneous syndactyly of the third and fourth fingers of the right hand, and bilateral lacrimal duct stenosis/aplasia....
Sun May 31, 2020 21:55
Abstract Cornelia de Lange syndrome (CdLS), Rubinstein–Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL , SMC1A , SMC3 , HDAC8 , RAD21 , ANKRD11 , and BRD4 , were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300 , have been associated with RSTS, whereas KBG results from variants in ANKRD11 . By exome...
Sun May 31, 2020 21:55
DNA damage‐induced apoptosis suppressor promotes activation of tyrosine phosphorylation of STAT3 through their interaction. Miconazole exerts an anti–cancer effect by suppressing STAT3 activation through inhibition of DDIAS/STAT3 binding. Abstract DNA damage‐induced apoptosis suppressor (DDIAS) facilitates the survival of lung cancer by suppressing apoptosis. Moreover, DDIAS promotes tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3) via their interaction. Here,...
Sun May 31, 2020 20:51
Abstract Background Juvenile idiopathic arthritis (JIA) is an autoimmune, chronic, inflammatory joint disease, affecting children and adolescents. Patients with JIA may have pain and fatigue in muscles. There are not studies evaluating the pressure pain thresholds (PPTs) of both masticatory muscles and temporomandibular joint (TMJ) in patients with JIA. Objective This study aimed to investigate PPTs of masticatory muscles and TMJ in subjects with JIA. Methods Fifty‐one JIA patients...
Sun May 31, 2020 14:00
Pooled targeted knockin of long DNA sequences with single-cell RNA sequencing was developed.
Mon Jun 01, 2020 10:05
Drug-induced pancreatic cancer cell senescence increased vulnerability to chemo- and immunotherapy.
Mon Jun 01, 2020 10:05
KTE-X19, an investigational chimeric antigen receptor T-cell therapy, has shown promising efficacy in patients with relapsed/refractory mantle cell lymphoma. Based on data from the ZUMA-2 trial, it is now under the FDA's priority review and could soon be a new standard of care for this rare hematologic malignancy.
Mon Jun 01, 2020 10:05
Adding a PD-L1 inhibitor to a standard targeted therapy for patients with untreated BRAF V600 mutation–positive advanced melanoma led to significantly improved progression-free survival, according to findings presented at the American Association for Cancer Research Virtual Annual Meeting Part I: April 27–28, 2020. The results add to evidence that combining immune checkpoint blockade with MEK–BRAF inhibition produces more clinically meaningful survival benefits than either MEK–BRAF or immune checkpoint...
Mon Jun 01, 2020 10:05
Capmatinib may be effective in patients with advanced non–small cell lung cancer who have MET exon 14 skipping mutations. In the phase II GEOMETRY mono-1 trial, the drug elicited high overall response rates and relatively durable responses in newly diagnosed and previously treated patients, including those with brain metastases.
Mon Jun 01, 2020 10:05
Tumors produce chemokines that attract neutrophils and cause them to undergo NETosis.
Mon Jun 01, 2020 10:05
In a phase I clinical trial, tumor-infiltrating lymphocyte therapy combined with the anti–PD-1 drug nivolumab was considered safe and tolerable—and exhibited preliminary signs of efficacy—in patients with stage IV or recurrent non–small cell lung cancer.
Mon Jun 01, 2020 10:05
Adding stereotactic ablative radiotherapy (SABR) to standard treatment slowed 6-month disease progression in men with hormone-sensitive metastatic prostate cancer, allowing them to delay androgen deprivation therapy, according to findings from the phase II ORIOLE trial. Larger studies are needed to determine if SABR, alone or combined with immunotherapies, can prevent new metastases in some patients.
Mon Jun 01, 2020 10:05
IL6 blockade helped promote the differentiation of red blood cell precursors, leading to reduced anemia and prolonged survival in a xenograft mouse model of AML. If validated in patients, the therapeutic strategy could reduce the need for blood transfusions, but it would not target the root cause of the disease.
Mon Jun 01, 2020 10:05
A new clinical trial suggests that the MEK inhibitor selumetinib induces partial responses in children with neurofibromatosis type 1 who have inoperable plexiform neurofibromas. The drug led to confirmed partial responses in 70% of patients; progression-free survival was 84% after 3 years.
Mon Jun 01, 2020 10:05
The breakage–fusion–bridge (BFB) cycle is linked to chromothripsis and yields chromosomal aberrations.
Mon Jun 01, 2020 10:05
TMPRSS2 is both the most frequently altered gene in primary prostate cancer and a critical factor enabling cellular infection by coronaviruses, including SARS-CoV-2. The modulation of its expression by sex steroids could contribute to the male predominance of severe infections, and given that TMPRSS2 has no known indispensable functions, and inhibitors are available, it is an appealing target for prevention or treatment of respiratory viral infections.
Mon Jun 01, 2020 10:05
In recent years, genomic-based blood testing has been heralded as a promising tool for early detection in a wide range of cancers. At the American Association for Cancer Research Virtual Annual Meeting I, two research teams independently developing such blood tests reported compelling data on the specificity and sensitivity of their tests.
Mon Jun 01, 2020 10:05
Using data from China, two studies suggest that people with cancer are more likely than the general population to contract COVID-19 and to develop more severe disease or die from it.
Mon Jun 01, 2020 10:05
Germline loss-of-function ELP1 variants were found in pediatric Sonic Hedgehog medulloblastomas.
Mon Jun 01, 2020 10:05
abstractCancer cells reprogram their metabolism to meet elevated energy demands and favor glycolysis for energy production. This boost in glycolytic flux supports proliferation, but also generates acid in the form of hydrogen ions that must be eliminated from the cytoplasm to maintain the alkaline intracellular pH (pHi) associated with transformation. To cope with acid production, tumor cells employ ion transport systems, including the family of sodium–hydrogen exchangers (NHE). Here, we identify...
Mon Jun 01, 2020 10:05
A report from the American Cancer Society reveals that colorectal cancer in people younger than 50 continues to increase, a trend that has spread to the 50-to-64 age group for the first time. Multiple lines of evidence indicate that obesity, often pinpointed as the cause, is not the only contributor.
Mon Jun 01, 2020 10:05
On March 30, 2020, the AACR Board of Directors provided a letter to the U.S. Congressional leadership on behalf of its members in response to the COVID-19 public health emergency.
Mon Jun 01, 2020 10:05
Cathepsin S (CTSS) aberrant activation or overexpression promotes non-Hodgkin lymphoma development.
Mon Jun 01, 2020 10:05
Surgery is the only curative option for stage I/II pancreatic cancer; nonetheless, most patients will experience a recurrence after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer, we performed whole-exome or targeted sequencing of 10 resected primary cancers and matched intrapancreatic recurrences or distant metastases. We identified that recurrent disease after adjuvant or first-line platinum therapy corresponds to an increased mutational...
Mon Jun 01, 2020 10:05
Summary:Although mutations in SF3B1 are the most common RNA-splicing factor mutations in cancer, determining the downstream missplicing events that drive tumorigenesis has remained challenging. Liu and colleagues present a model by which mutant SF3B1 tumors displayed high levels of oncogenic MYC activity through the missplicing of PP2A-B56α, a key post-translational regulator of MYC stability, providing a new therapeutic target and driver of SF3B1-mediated tumorigenesis. See related article by...
Mon Jun 01, 2020 10:05
Epithelial plasticity, reversible modulation of a cell's epithelial and mesenchymal features, is associated with tumor metastasis and chemoresistance, leading causes of cancer mortality. Although different master transcription factors and epigenetic modifiers have been implicated in this process in various contexts, the extent to which a unifying, generalized mechanism of transcriptional regulation underlies epithelial plasticity remains largely unknown. Here, through targeted CRISPR/Cas9 screening,...
Mon Jun 01, 2020 10:05
Lurbinectedin produced responses in 35.2% of 105 patients with relapsed small-cell lung cancer.
Mon Jun 01, 2020 10:05
Cysteine depletion caused ferroptosis in human pancreatic cancer cells and improved survival in mice.
Mon Jun 01, 2020 10:05
Many oncogenes contain multiple individually weak mutations that collectively promote oncogenesis.
Mon Jun 01, 2020 10:05
PARP1 inhibitors that clash with a specific helix in the helical domain prevent release from DNA.
Mon Jun 01, 2020 10:05
Neoadjuvant immunotherapy was safe and showed evidence of efficacy in stage I–III colon cancer.
Mon Jun 01, 2020 10:05
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