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https://www.readbyqxmd.com/read/28162770/gene-essentiality-profiling-reveals-gene-networks-and-synthetic-lethal-interactions-with-oncogenic-ras
#1
Tim Wang, Haiyan Yu, Nicholas W Hughes, Bingxu Liu, Arek Kendirli, Klara Klein, Walter W Chen, Eric S Lander, David M Sabatini
The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) cell lines. Sets of genes with correlated patterns of essentiality across the lines reveal new gene relationships, the essential substrates of enzymes, and the molecular functions of uncharacterized proteins...
February 1, 2017: Cell
https://www.readbyqxmd.com/read/28187292/snapshot-circulating-tumor-cells
#2
Caroline Dive, Ged Brady
Circulating tumor cells in the blood of patients are both signal flares for the existence of a tumor and harbingers of metastasis. With recent technological developments, these cells can be isolated and analyzed to provide insights into the biology of cancer spread and response to therapy and to offer new avenues for blood biomarker development.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187291/the-principles-of-engineering-immune-cells-to-treat-cancer
#3
REVIEW
Wendell A Lim, Carl H June
Chimeric antigen receptor (CAR) T cells have proven that engineered immune cells can serve as a powerful new class of cancer therapeutics. Clinical experience has helped to define the major challenges that must be met to make engineered T cells a reliable, safe, and effective platform that can be deployed against a broad range of tumors. The emergence of synthetic biology approaches for cellular engineering is providing us with a broadly expanded set of tools for programming immune cells. We discuss how these tools could be used to design the next generation of smart T cell precision therapeutics...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187290/primary-adaptive-and-acquired-resistance-to-cancer-immunotherapy
#4
REVIEW
Padmanee Sharma, Siwen Hu-Lieskovan, Jennifer A Wargo, Antoni Ribas
Cancer immunotherapy can induce long lasting responses in patients with metastatic cancers of a wide range of histologies. Broadening the clinical applicability of these treatments requires an improved understanding of the mechanisms limiting cancer immunotherapy. The interactions between the immune system and cancer cells are continuous, dynamic, and evolving from the initial establishment of a cancer cell to the development of metastatic disease, which is dependent on immune evasion. As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187289/tumorigenic-and-immunosuppressive-effects-of-endoplasmic-reticulum-stress-in-cancer
#5
REVIEW
Juan R Cubillos-Ruiz, Sarah E Bettigole, Laurie H Glimcher
Malignant cells utilize diverse strategies that enable them to thrive under adverse conditions while simultaneously inhibiting the development of anti-tumor immune responses. Hostile microenvironmental conditions within tumor masses, such as nutrient deprivation, oxygen limitation, high metabolic demand, and oxidative stress, disturb the protein-folding capacity of the endoplasmic reticulum (ER), thereby provoking a cellular state of "ER stress." Sustained activation of ER stress sensors endows malignant cells with greater tumorigenic, metastatic, and drug-resistant capacity...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187288/emerging-biological-principles-of-metastasis
#6
REVIEW
Arthur W Lambert, Diwakar R Pattabiraman, Robert A Weinberg
Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and we highlight the general principles of metastasis that have begun to emerge...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187287/understanding-the-intersections-between-metabolism-and-cancer-biology
#7
REVIEW
Matthew G Vander Heiden, Ralph J DeBerardinis
Transformed cells adapt metabolism to support tumor initiation and progression. Specific metabolic activities can participate directly in the process of transformation or support the biological processes that enable tumor growth. Exploiting cancer metabolism for clinical benefit requires defining the pathways that are limiting for cancer progression and understanding the context specificity of metabolic preferences and liabilities in malignant cells. Progress toward answering these questions is providing new insight into cancer biology and can guide the more effective targeting of metabolism to help patients...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187286/endogenous-dna-damage-as-a-source-of-genomic-instability-in-cancer
#8
REVIEW
Anthony Tubbs, André Nussenzweig
Genome instability, defined as higher than normal rates of mutation, is a double-edged sword. As a source of genetic diversity and natural selection, mutations are beneficial for evolution. On the other hand, genomic instability can have catastrophic consequences for age-related diseases such as cancer. Mutations arise either from inactivation of DNA repair pathways or in a repair-competent background due to genotoxic stress from celluar processes such as transcription and replication that overwhelm high-fidelity DNA repair...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187285/transcriptional-addiction-in-cancer
#9
REVIEW
James E Bradner, Denes Hnisz, Richard A Young
Cancer arises from genetic alterations that invariably lead to dysregulated transcriptional programs. These dysregulated programs can cause cancer cells to become highly dependent on certain regulators of gene expression. Here, we discuss how transcriptional control is disrupted by genetic alterations in cancer cells, why transcriptional dependencies can develop as a consequence of dysregulated programs, and how these dependencies provide opportunities for novel therapeutic interventions in cancer.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187284/clonal-heterogeneity-and-tumor-evolution-past-present-and-the-future
#10
REVIEW
Nicholas McGranahan, Charles Swanton
Intratumor heterogeneity, which fosters tumor evolution, is a key challenge in cancer medicine. Here, we review data and technologies that have revealed intra-tumor heterogeneity across cancer types and the dynamics, constraints, and contingencies inherent to tumor evolution. We emphasize the importance of macro-evolutionary leaps, often involving large-scale chromosomal alterations, in driving tumor evolution and metastasis and consider the role of the tumor microenvironment in engendering heterogeneity and drug resistance...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187283/applications-of-immunogenomics-to-cancer
#11
REVIEW
X Shirley Liu, Elaine R Mardis
Cancer immunogenomics originally was framed by research supporting the hypothesis that cancer mutations generated novel peptides seen as "non-self" by the immune system. The search for these "neoantigens" has been facilitated by the combination of new sequencing technologies, specialized computational analyses, and HLA binding predictions that evaluate somatic alterations in a cancer genome and interpret their ability to produce an immune-stimulatory peptide. The resulting information can characterize a tumor's neoantigen load, its cadre of infiltrating immune cell types, the T or B cell receptor repertoire, and direct the design of a personalized therapeutic...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187282/implementing-genome-driven-oncology
#12
REVIEW
David M Hyman, Barry S Taylor, José Baselga
Early successes in identifying and targeting individual oncogenic drivers, together with the increasing feasibility of sequencing tumor genomes, have brought forth the promise of genome-driven oncology care. As we expand the breadth and depth of genomic analyses, the biological and clinical complexity of its implementation will be unparalleled. Challenges include target credentialing and validation, implementing drug combinations, clinical trial designs, targeting tumor heterogeneity, and deploying technologies beyond DNA sequencing, among others...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187281/how-much-longer-will-we-put-up-with-100-000-cancer-drugs
#13
Paul Workman, Giulio F Draetta, Jan H M Schellens, René Bernards
The spiraling cost of new drugs mandates a fundamentally different approach to keep lifesaving therapies affordable for cancer patients. We call here for the formation of new relationships between academic drug discovery centers and commercial partners, which can accelerate the development of truly transformative drugs at sustainable prices.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187280/cancer-clinical-trials-the-rear-view-mirror-and-the-crystal-ball
#14
Dave Cescon, Lillian L Siu
Clinical trials are key to translating scientific advances into progress in cancer research and care. Confronted by developments in basic science, the landscape of clinical cancer research is rapidly evolving. Here, we review recent changes in clinical trials' design and conduct, and we forecast future directions toward personalized and global impact.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187279/next-generation-sequencing-of-circulating-tumor-dna-for-early-cancer-detection
#15
Alexander M Aravanis, Mark Lee, Richard D Klausner
Curative therapies are most successful when cancer is diagnosed and treated at an early stage. We advocate that technological advances in next-generation sequencing of circulating, tumor-derived nucleic acids hold promise for addressing the challenge of developing safe and effective cancer screening tests.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187278/translating-germline-cancer-risk-into-precision-prevention
#16
Matthew B Yurgelun, Georgia Chenevix-Trench, Scott M Lippman
Study of the biology of tumors caused by germline mutations has led to recent paradigm-changing therapy and is driving precision prevention efforts, including immune oncology and early detection research. Here, we explore recent biologic advances that are redefining the spectrum of cancers linked to various hereditary predisposition syndromes and can be leveraged to improve personalized risk assessment and develop novel interventions to prevent or intercept cancer.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187277/where-is-the-future-of-drug-discovery-for-cancer
#17
(no author information available yet)
With both small molecules and biologics succeeding in trials and in the clinic, the scope of drug discovery in cancer is changing. We asked a group of researchers to share their visions for how to identify new targets and how to approach taming them.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187276/a-convergence-of-genetics-and-epigenetics-in-cancer
#18
(no author information available yet)
What is at the forefront of the intersection of genetics and epigenetics in cancer and how do we use what we've learned to devise new cures? These are the questions Cell editor Jiaying Tan posed to Jan Korbel and Charles Roberts. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187275/poisoning-the-devil
#19
Zhu Chen, Sai-Juan Chen
No abstract text is available yet for this article.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28187274/pdgfra-antibody-for-soft-tissue-sarcoma
#20
Lillian R Klug, Michael C Heinrich
Lartruvo (olaratumab) is a monoclonal antibody against the extracellular domain of PDGFRA. Olaratumab blocks ligand binding and thereby inhibits activation of PDGFRA kinase activity. Pre-clinically, this antibody inhibited PDGFRA-dependent tumor growth. In a randomized Phase II study, adding olaratumab to doxorubicin chemotherapy significantly improved overall survival, leading to FDA approval.
February 9, 2017: Cell
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