Angiosarcoma Project researchers have uncovered some details about the molecular underpinnings of angiosarcoma, pointing to potential therapeutic options. Their work also suggests that a research model based on direct patient participation can overcome common barriers to studying rare diseases.
Wed Apr 01, 2020 10:05
Summary:In this issue, Singh and colleagues describe a novel tumor-intrinsic mechanism of resistance to chimericantigen receptor (CAR) T-cell therapy targeting CD19 in B-cell malignancies. They show that reduced expression of death receptor genes in the tumors mediates resistance to killing by CAR T cells, leads to progressive CAR T-cell dysfunction, and is associated with unfavorable clinical outcome in patients. See related article by Singh et al., p. 552.
Wed Apr 01, 2020 10:05
Previously unidentified breast cancer subtypes that may be linked to prognosis were identified using imaging mass cytometry, a recently invented and rapidly developing technique that allows spatial relationships among cells expressing selected markers to be determined.
Wed Apr 01, 2020 10:05
AKT inhibitors have promising activity in AKT1E17K-mutant estrogen receptor (ER)–positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinical outcomes of patients with matched AKT1E17K-mutant (n = 153) and AKT1–wild-type (n = 302) metastatic breast cancer. AKT1-mutant cases had similar adjusted overall survival (OS) compared...
Wed Apr 01, 2020 10:05
The signature features of pancreatic ductal adenocarcinoma (PDAC) are its fibroinflammatory stroma, poor immune activity, and dismal prognosis. We show that acute activation of Myc in indolent pancreatic intraepithelial neoplasm (PanIN) epithelial cells in vivo is, alone, sufficient to trigger immediate release of instructive signals that together coordinate changes in multiple stromal and immune-cell types and drive transition to pancreatic adenocarcinomas that share all the characteristic stromal...
Wed Apr 01, 2020 10:05
Antoni Ribas, MD, PhD, discusses the biological discoveries that have led to new therapies for melanoma—and the future of treatment for the disease.
Wed Apr 01, 2020 10:05
The anti-HER2–drug conjugate trastuzumab deruxtecan (T-DXd) was effective in HER2-low breast cancer.
Wed Apr 01, 2020 10:05
Having shown preclinical promise, the first clinical data are now in on natural killer cells equipped with a chimeric antigen receptor targeting CD19. Albeit in a small number of patients so far, the experimental immunotherapy has elicited a high response rate with little to no toxicity.
Wed Apr 01, 2020 10:05
Glycolysis was downregulated in normal but not transformed cells upon transfer to softer substrates.
Wed Apr 01, 2020 10:05
NUAK1 inhibition caused buildup of nonproductive stalled transcription complexes in high-MYC cells.
Wed Apr 01, 2020 10:05
Summary:In this issue, Smyth and colleagues investigate the natural history of AKT1-mutant metastatic breast cancer using the AACR Project GENIE, a novel research platform comprised of real-world, clinicogenomic data. A rare subset of tumors, AKT1-mutant breast cancers demonstrated similar clinical and demographic characteristics and overall survival as AKT1–wild-type tumors, but a longer duration of therapy on mTOR inhibitors. See related article by Smyth et al., p. 526.
Wed Apr 01, 2020 10:05
In response to glucose starvation, AMPK inhibited lipid peroxidation-associated ferroptosis.
Wed Apr 01, 2020 10:05
Summary:In this issue of Cancer Discovery, Sodir and colleagues employ a pancreatic ductal adenocarcinoma mouse model with mutant KRAS and inducible MYC to demonstrate that MYC acts as a reversible driver of malignant tumor progression. Abrogation of MYC triggers rapid regression and disassembly of the ensemble tumor through both cancer cell–intrinsic and cancer cell–extrinsic mechanisms, providing a compelling rationale for therapeutic targeting of MYC. See related article by Sodir et al., p....
Wed Apr 01, 2020 10:05
Structural analyses showed that HPF1 contributed amino acid residues to the PARP1/2 active site.
Wed Apr 01, 2020 10:05
The therapeutic armamentarium of acute myeloid leukemia (AML) has rapidly expanded in the past few years, driven largely by translational research into its genomic landscape and an improved understanding of mechanisms of resistance to conventional therapies. However, primary and secondary drug resistance remains a substantial problem for most patients. Research into the mechanisms of resistance to these new agents is informing the development of the next class of AML drugs and the design of combination...
Wed Apr 01, 2020 10:05
Metastatic cells were remniscient of earlier developmental stages than primary tumor cells.
Wed Apr 01, 2020 10:05
Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front resistance as well as relapse following initial response demonstrates the need for a deeper understanding of resistance mechanisms. In the present study, we report that responses to venetoclax +azacitidine in patients with AML correlate closely with developmental stage, where phenotypically primitive AML is sensitive, but monocytic AML is more...
Wed Apr 01, 2020 10:05
PD-1 depletion or nivolumab treatment dampened morphine antinociception in mice and rhesus macaques.
Wed Apr 01, 2020 10:05
Disease recurrence causes significant mortality in B-progenitor acute lymphoblastic leukemia (B-ALL). Genomic analysis of matched diagnosis and relapse samples shows relapse often arising from minor diagnosis subclones. However, why therapy eradicates some subclones while others survive and progress to relapse remains obscure. Elucidation of mechanisms underlying these differing fates requires functional analysis of isolated subclones. Here, large-scale limiting dilution xenografting of diagnosis...
Wed Apr 01, 2020 10:05
In a phase Ib trial, osimertinib plus savolitinib showed efficacy in non–small cell lung cancer.
Wed Apr 01, 2020 10:05
A hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant stroma comprised of diverse cell types that enable or suppress tumor progression. Here, we explored the role of oncogenic KRAS in protumorigenic signaling interactions between cancer cells and host cells. We show that KRAS mutation (KRAS*) drives cell-autonomous expression of type I cytokine receptor complexes (IL2r–IL4rα and IL2r–IL13rα1) in cancer cells that in turn are capable of receiving cytokine growth signals (IL4 or IL13)...
Wed Apr 01, 2020 10:05
Introduction. Air pollution has been identified as a serious public health problem in the world’s major metropolises. Recent studies have shown that airborne particle concentrations are associated with a wide range of effects on human health, including increased hospital admissions for respiratory disease, enhanced asthma episodes, decreased lung function, and increased mortality. Objective. To relate the levels of air pollution and hospital admissions for cardiovascular and respiratory diseases...
Wed Apr 01, 2020 03:20
Abstract Aiming to uncover a shared genetic basis of abdominal obesity and osteoporosis, we performed a bivariate GWAS meta-analysis of femoral neck BMD (FNK-BMD) and trunk fat mass adjusted by trunk lean mass (TFMadj) in 11,496 subjects from 6 samples, followed by in silico replication in the large-scale UK Biobank (UKB) cohort. A series of functional investigations were conducted on the identified variants. Bivariate GWAS meta-analysis identified two novel pleiotropic loci 12q15...
Wed Apr 01, 2020 03:00
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