Showing papers in "Cancer Cell in 2015"

TL;DR: The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands, so drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer regressions.

TL;DR: The tremendous clinical success of checkpoint blockers illustrates the potential of reestablishing latent immunosurveillance for cancer therapy, and their in-depth comprehension will facilitate the design of novel combinatorial regimens with improved clinical efficacy.

TL;DR: This review discusses the molecular/cellular pathways identified so far whereby macrophages mediate therapeutic responses and therapeutics impacting macrophage presence and/or bioactivity have shown promise in preclinical models and are now being evaluated in the clinic.

TL;DR: The processes shaping the cancer genome are explored, placing these within the context of tumor evolution and their impact on intratumor heterogeneity and drug development.

TL;DR: The molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.

TL;DR: This work identifies an NF-KappaB Interacting LncRNA (NKILA), which is upregulated by NF-κB, binds to NF-σκB/IκBs, and directly masks phosphorylation motifs of IKKB, thereby inhibiting IKK-induced IκBosphorylation and NF-kkB activation.

TL;DR: It is demonstrated that synthesis of the antioxidant glutathione (GSH), driven by GCLM, is required for cancer initiation and combined inhibition of GSH and thioredoxin antioxidant pathways leads to a synergistic cancer cell death in vitro and vivo, demonstrating the importance of these two antioxidants to tumor progression and as potential targets for therapeutic intervention.

TL;DR: This research highlights the need to understand more fully the role of language in the development of post-traumatic stress disorder and the role that language can play in the recovery.

TL;DR: The results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based “liquid biopsies”.

TL;DR: In this article, the authors used an in vivo "stress test" to challenge CD19-targeted T cells, and studied the functionality and persistence imparted by seven different CAR structures providing CD28 and/or 4-1BB costimulation.

TL;DR: A critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment is concluded, indicating a critical role in the growth of cancer cell growth under low-oxygen and lipid-depleted conditions.

TL;DR: A comprehensive analysis of lncRNA alterations at transcriptional, genomic, and epigenetic levels in 5,037 human tumor specimens across 13 cancer types from The Cancer Genome Atlas suggests that the expression and dysregulation of lNCRNAs are highly cancer type specific compared with protein-coding genes.

TL;DR: It is proposed that paradoxically activated MAFs provide a “safe haven” for melanoma cells to tolerate BRAF inhibition and are linked to “paradoxical” activation of melanoma-associated fibroblasts by PLX4720 and the promotion of matrix production and remodeling leading to elevated integrin β1/FAK/Src signaling in melanoma Cells.

TL;DR: It is reported that mutations affecting the splicing factor S RSF2 directly impair hematopoietic differentiation in vivo, which is not due to SRSF2 loss of function, and this data provide a mechanistic link between a mutant spliceosomal protein, alterations in thesplicing of key regulators, and impaired hematoiesis.

TL;DR: The effects of several cross-tumor nonsynonymous RNA editing events on cell viability are experimentally demonstrated and the evidence that RNA editing could selectively affect drug sensitivity is provided, highlighting RNA editing as an exciting theme for investigating cancer mechanisms, biomarkers, and treatments.

TL;DR: A proliferation screen of cell lines representing a number of tumor types indicated that small cell lung carcinoma (SCLC) is sensitive to LSD1 inhibition, and a subset of SCLC lines and primary samples that undergo growth inhibition in response to GSK2879552 exhibit DNA hypomethylation of a signature set of probes, suggesting this may be used as a predictive biomarker of activity.

TL;DR: The results suggest that PF-06463922 will be highly effective for the treatment of patients with ALK-driven lung cancers, including those who relapsed on clinically available ALK inhibitors because of secondary ALK kinase domain mutations and/or brain metastases.

TL;DR: By integrating massive sequencing strategies, this work provides a comprehensive characterization of driver genetic alterations (somatic point mutations, copy number alterations, and gene fusions) in ALK(-) ALCLs and identifies activating mutations of JAK1 and/or STAT3 genes that led to constitutive activation of the JAK/STAT3 pathway.

TL;DR: A compound that equally inhibits both sites of mutant RAF dimers inhibits tumors driven by either class of mutants or those BRAF V600E tumors with dimer-dependent acquired resistance to monomer-specific inhibitors.

TL;DR: This work identifies SMO mutations in 50% of resistant BCCs and shows that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors, setting the stage for the clinical use of GLI antagonists.

TL;DR: Genomic analysis of tumor biopsies revealed that vismodegib resistance is associated with Hedgehog (Hh) pathway reactivation, predominantly through mutation of the drug target SMO and to a lesser extent through concurrent copy number changes in SUFU and GLI2.

TL;DR: It is found that 2-HG depletion did not inhibit growth of several IDH1 mutant solid cancer types, and NAD+ depletion is identified as a metabolic susceptibility of IDH 1 mutant cancers.

TL;DR: A comprehensive assessment of the scope of targeted therapeutic agents in a large pan-cancer cohort and an in silico prescription strategy based on identification of the driver alterations in each tumor and their druggability options is developed.

TL;DR: It is shown that augmenting oxidant stress in normal cells limits tumor initiation and progression, and strategic targeting of antioxidant systems may undermine survival of new tumor cells.

TL;DR: An adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41 is described, suggesting that they constitute a family of tumor suppressor genes.

TL;DR: CB-5083 causes modulation of key p97-related pathways, induces apoptosis, and has antitumor activity in a broad range of both hematological and solid tumor models, providing a potential strategy for patient selection.

TL;DR: It is elucidated that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases and provides potential therapeutic targets to block progression toward osteolytic metastases.

TL;DR: It is shown that melanomas acquire resistance to combined BRAF and MEK inhibition by augmenting or combining mechanisms of single-agent BRAFi resistance, and melanoma cell lines selected for resistance to BRA Fi+MEKi, but not those to BRAFi alone, displayed robust drug addiction, providing a potentially exploitable therapeutic opportunity.

TL;DR: It is revealed that distinct Fcγ receptor (FcγRs) dependency and mechanisms account for the in vivo activity of anti- PD-1 versus anti-PD-L1 Abs, which show augmented anti-tumor activity when activating F cγR binding is introduced into the molecules.

TL;DR: In this article, the authors report the development of highly potent and orally bioavailable small-molecule inhibitors of the menin-MLL interaction, MI-463 and MI-503, and show their profound effects in mixed lineage leukemia cells and substantial survival benefit in mouse models of MLL leukemia.