Use the keywords feature with a free QxMD account.
Use Read by QxMD to access full text via your institution or open access sources.
Read also provides personalized recommendations to keep you up to date in your field.
Existing User
Sign InNew to Read
Sign Up#1
JOURNAL ARTICLE
Abhinav Jaiswal, Akanksha Verma, Ruth Dannenfelser, Marit Melssen, Itay Tirosh, Benjamin Izar, Tae-Gyun Kim, Christopher J Nirschl, K Sanjana P Devi, Walter C Olson, Craig L Slingluff, Victor H Engelhard, Levi Garraway, Aviv Regev, Kira Minkis, Charles H Yoon, Olga Troyanskaya, Olivier Elemento, Mayte Suárez-Fariñas, Niroshana Anandasabapathy
There is a need for better classification and understanding of tumor-infiltrating lymphocytes (TILs). Here, we applied advanced functional genomics to interrogate 9,000 human tumors and multiple single-cell sequencing sets using benchmarked T cell states, comprehensive T cell differentiation trajectories, human and mouse vaccine responses, and other human TILs. Compared with other T cell states, enrichment of T memory/resident memory programs was observed across solid tumors. Trajectory analysis of single-cell melanoma CD8+ TILs also identified a high fraction of memory/resident memory-scoring TILs in anti-PD-1 responders, which expanded post therapy...
May 9, 2022: Cancer Cell
#2
JOURNAL ARTICLE
Eran Hodis, Elena Torlai Triglia, John Y H Kwon, Tommaso Biancalani, Labib R Zakka, Saurabh Parkar, Jan-Christian Hütter, Lorenzo Buffoni, Toni M Delorey, Devan Phillips, Danielle Dionne, Lan T Nguyen, Denis Schapiro, Zoltan Maliga, Connor A Jacobson, Ayal Hendel, Orit Rozenblatt-Rosen, Martin C Mihm, Levi A Garraway, Aviv Regev
Establishing causal relationships between genetic alterations of human cancers and specific phenotypes of malignancy remains a challenge. We sequentially introduced mutations into healthy human melanocytes in up to five genes spanning six commonly disrupted melanoma pathways, forming nine genetically distinct cellular models of melanoma. We connected mutant melanocyte genotypes to malignant cell expression programs in vitro and in vivo, replicative immortality, malignancy, rapid tumor growth, pigmentation, metastasis, and histopathology...
April 29, 2022: Science
#3
JOURNAL ARTICLE
Elizabeth H Stover, Coyin Oh, Paula Keskula, Atish D Choudhury, Yuen-Yi Tseng, Viktor A Adalsteinsson, Jens G Lohr, Aaron R Thorner, Matthew Ducar, Gregory V Kryukov, Gavin Ha, Mara Rosenberg, Samuel S Freeman, Zhenwei Zhang, Xiaoyun Wu, Eliezer M Van Allen, David Y Takeda, Massimo Loda, Chin-Lee Wu, Mary-Ellen Taplin, Levi A Garraway, Jesse S Boehm, Franklin W Huang
BACKGROUND: Primary and metastatic prostate cancers have low mutation rates and recurrent alterations in a small set of genes, enabling targeted sequencing of prostate cancer-associated genes as an efficient approach to characterizing patient samples (compared to whole-exome and whole-genome sequencing). For example, targeted sequencing provides a flexible, rapid, and cost-effective method for genomic assessment of patient-derived cell lines to evaluate fidelity to initial patient tumor samples...
April 2022: Prostate
#4
JOURNAL ARTICLE
John D Carpten, Lola Fashoyin-Aje, Levi A Garraway, Robert Winn
No abstract text is available yet for this article.
October 2021: Nature Reviews. Cancer
#5
JOURNAL ARTICLE
Jennifer A Lo, Masayoshi Kawakubo, Vikram R Juneja, Mack Y Su, Tal H Erlich, Martin W LaFleur, Lajos V Kemeny, Mamunur Rashid, Mohsen Malehmir, S Alireza Rabi, Rumya Raghavan, Jennifer Allouche, Gyulnara Kasumova, Dennie T Frederick, Kristen E Pauken, Qing Yu Weng, Marcelo Pereira da Silva, Yu Xu, Anita A J van der Sande, Whitney Silkworth, Elisabeth Roider, Edward P Browne, David J Lieb, Belinda Wang, Levi A Garraway, Catherine J Wu, Keith T Flaherty, Constance E Brinckerhoff, David W Mullins, David J Adams, Nir Hacohen, Mai P Hoang, Genevieve M Boland, Gordon J Freeman, Arlene H Sharpe, Dieter Manstein, David E Fisher
Although immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 (PD-1), can deliver durable antitumor effects, most patients with cancer fail to respond. Recent studies suggest that ICI efficacy correlates with a higher load of tumor-specific neoantigens and development of vitiligo in patients with melanoma. Here, we report that patients with low melanoma neoantigen burdens who responded to ICI had tumors with higher expression of pigmentation-related genes. Moreover, expansion of peripheral blood CD8+ T cell populations specific for melanocyte antigens was observed only in patients who responded to anti-PD-1 therapy, suggesting that ICI can promote breakdown of tolerance toward tumor-lineage self-antigens...
February 17, 2021: Science Translational Medicine
#6
JOURNAL ARTICLE
Syed H Zaidi, Tabitha A Harrison, Amanda I Phipps, Robert Steinfelder, Quang M Trinh, Conghui Qu, Barbara L Banbury, Peter Georgeson, Catherine S Grasso, Marios Giannakis, Jeremy B Adams, Elizabeth Alwers, Efrat L Amitay, Richard T Barfield, Sonja I Berndt, Ivan Borozan, Hermann Brenner, Stefanie Brezina, Daniel D Buchanan, Yin Cao, Andrew T Chan, Jenny Chang-Claude, Charles M Connolly, David A Drew, Alton Brad Farris, Jane C Figueiredo, Amy J French, Charles S Fuchs, Levi A Garraway, Steve Gruber, Mark A Guinter, Stanley R Hamilton, Sophia Harlid, Lawrence E Heisler, Akihisa Hidaka, John L Hopper, Wen-Yi Huang, Jeroen R Huyghe, Mark A Jenkins, Paul M Krzyzanowski, Mathieu Lemire, Yi Lin, Xuemei Luo, Elaine R Mardis, John D McPherson, Jessica K Miller, Victor Moreno, Xinmeng Jasmine Mu, Reiko Nishihara, Nickolas Papadopoulos, Danielle Pasternack, Michael J Quist, Adilya Rafikova, Emma E G Reid, Eve Shinbrot, Brian H Shirts, Lincoln D Stein, Cherie D Teney, Lee Timms, Caroline Y Um, Bethany Van Guelpen, Megan Van Tassel, Xiaolong Wang, David A Wheeler, Christina K Yung, Li Hsu, Shuji Ogino, Andrea Gsur, Polly A Newcomb, Steven Gallinger, Michael Hoffmeister, Peter T Campbell, Stephen N Thibodeau, Wei Sun, Thomas J Hudson, Ulrike Peters
Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR = 0...
July 20, 2020: Nature Communications
#7
JOURNAL ARTICLE
Benjamin Izar, Itay Tirosh, Elizabeth H Stover, Isaac Wakiro, Michael S Cuoco, Idan Alter, Christopher Rodman, Rachel Leeson, Mei-Ju Su, Parin Shah, Marcin Iwanicki, Sarah R Walker, Abhay Kanodia, Johannes C Melms, Shaolin Mei, Jia-Ren Lin, Caroline B M Porter, Michal Slyper, Julia Waldman, Livnat Jerby-Arnon, Orr Ashenberg, Titus J Brinker, Caitlin Mills, Meri Rogava, Sébastien Vigneau, Peter K Sorger, Levi A Garraway, Panagiotis A Konstantinopoulos, Joyce F Liu, Ursula Matulonis, Bruce E Johnson, Orit Rozenblatt-Rosen, Asaf Rotem, Aviv Regev
Malignant abdominal fluid (ascites) frequently develops in women with advanced high-grade serous ovarian cancer (HGSOC) and is associated with drug resistance and a poor prognosis1 . To comprehensively characterize the HGSOC ascites ecosystem, we used single-cell RNA sequencing to profile ~11,000 cells from 22 ascites specimens from 11 patients with HGSOC. We found significant inter-patient variability in the composition and functional programs of ascites cells, including immunomodulatory fibroblast sub-populations and dichotomous macrophage populations...
August 2020: Nature Medicine
#8
David Liu, Bastian Schilling, Derek Liu, Antje Sucker, Elisabeth Livingstone, Livnat Jerby-Arnon, Lisa Zimmer, Ralf Gutzmer, Imke Satzger, Carmen Loquai, Stephan Grabbe, Natalie Vokes, Claire A Margolis, Jake Conway, Meng Xiao He, Haitham Elmarakeby, Felix Dietlein, Diana Miao, Adam Tracy, Helen Gogas, Simone M Goldinger, Jochen Utikal, Christian U Blank, Ricarda Rauschenberg, Dagmar von Bubnoff, Angela Krackhardt, Benjamin Weide, Sebastian Haferkamp, Felix Kiecker, Ben Izar, Levi Garraway, Aviv Regev, Keith Flaherty, Annette Paschen, Eliezer M Van Allen, Dirk Schadendorf
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
July 2020: Nature Medicine
#9
MULTICENTER STUDY
Seth A Wander, Ofir Cohen, Xueqian Gong, Gabriela N Johnson, Jorge E Buendia-Buendia, Maxwell R Lloyd, Dewey Kim, Flora Luo, Pingping Mao, Karla Helvie, Kailey J Kowalski, Utthara Nayar, Adrienne G Waks, Stephen H Parsons, Ricardo Martinez, Lacey M Litchfield, Xiang S Ye, Chunping Yu, Valerie M Jansen, John R Stille, Patricia S Smith, Gerard J Oakley, Quincy S Chu, Gerald Batist, Melissa E Hughes, Jill D Kremer, Levi A Garraway, Eric P Winer, Sara M Tolaney, Nancy U Lin, Sean G Buchanan, Nikhil Wagle
Mechanisms driving resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in hormone receptor-positive (HR+ ) breast cancer have not been clearly defined. Whole-exome sequencing of 59 tumors with CDK4/6i exposure revealed multiple candidate resistance mechanisms including RB1 loss, activating alterations in AKT1, RAS, AURKA, CCNE2, ERBB2 , and FGFR2 , and loss of estrogen receptor expression. In vitro experiments confirmed that these alterations conferred CDK4/6i resistance. Cancer cells cultured to resistance with CDK4/6i also acquired RB1, KRAS, AURKA , or CCNE2 alterations, which conferred sensitivity to AURKA, ERK, or CHEK1 inhibition...
August 2020: Cancer Discovery
#10
JOURNAL ARTICLE
David P Nusinow, John Szpyt, Mahmoud Ghandi, Christopher M Rose, E Robert McDonald, Marian Kalocsay, Judit Jané-Valbuena, Ellen Gelfand, Devin K Schweppe, Mark Jedrychowski, Javad Golji, Dale A Porter, Tomas Rejtar, Y Karen Wang, Gregory V Kryukov, Frank Stegmeier, Brian K Erickson, Levi A Garraway, William R Sellers, Steven P Gygi
Proteins are essential agents of biological processes. To date, large-scale profiling of cell line collections including the Cancer Cell Line Encyclopedia (CCLE) has focused primarily on genetic information whereas deep interrogation of the proteome has remained out of reach. Here, we expand the CCLE through quantitative profiling of thousands of proteins by mass spectrometry across 375 cell lines from diverse lineages to reveal information undiscovered by DNA and RNA methods. We observe unexpected correlations within and between pathways that are largely absent from RNA...
January 23, 2020: Cell
#11
JOURNAL ARTICLE
David Liu, Bastian Schilling, Derek Liu, Antje Sucker, Elisabeth Livingstone, Livnat Jerby-Arnon, Lisa Zimmer, Ralf Gutzmer, Imke Satzger, Carmen Loquai, Stephan Grabbe, Natalie Vokes, Claire A Margolis, Jake Conway, Meng Xiao He, Haitham Elmarakeby, Felix Dietlein, Diana Miao, Adam Tracy, Helen Gogas, Simone M Goldinger, Jochen Utikal, Christian U Blank, Ricarda Rauschenberg, Dagmar von Bubnoff, Angela Krackhardt, Benjamin Weide, Sebastian Haferkamp, Felix Kiecker, Ben Izar, Levi Garraway, Aviv Regev, Keith Flaherty, Annette Paschen, Eliezer M Van Allen, Dirk Schadendorf
Immune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort of patients with melanoma (n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcriptome sequencing of pre-treatment tumors. We found that tumor mutational burden as a predictor of response was confounded by melanoma subtype, whereas multiple novel genomic and transcriptomic features predicted selective response, including features associated with MHC-I and MHC-II antigen presentation...
December 2019: Nature Medicine
#12
REVIEW
Alan Huang, Levi A Garraway, Alan Ashworth, Barbara Weber
The first wave of genetically targeted therapies for cancer focused on drugging gene products that are recurrently mutated in specific cancer types. However, mutational analysis of tumours has largely been exhausted as a strategy for the identification of new cancer targets that are druggable with conventional approaches. Furthermore, some known genetic drivers of cancer have not been directly targeted yet owing to their molecular structure (undruggable oncogenes) or because they result in functional loss (tumour suppressor genes)...
January 2020: Nature Reviews. Drug Discovery
#13
JOURNAL ARTICLE
Haoxin Li, Kevin Bullock, Carino Gurjao, David Braun, Sachet A Shukla, Dominick Bossé, Aly-Khan A Lalani, Shuba Gopal, Chelsea Jin, Christine Horak, Megan Wind-Rotolo, Sabina Signoretti, David F McDermott, Gordon J Freeman, Eliezer M Van Allen, Stuart L Schreiber, F Stephen Hodi, William R Sellers, Levi A Garraway, Clary B Clish, Toni K Choueiri, Marios Giannakis
Despite remarkable success of immune checkpoint inhibitors, the majority of cancer patients have yet to receive durable benefits. Here, in order to investigate the metabolic alterations in response to immune checkpoint blockade, we comprehensively profile serum metabolites in advanced melanoma and renal cell carcinoma patients treated with nivolumab, an antibody against programmed cell death protein 1 (PD1). We identify serum kynurenine/tryptophan ratio increases as an adaptive resistance mechanism associated with worse overall survival...
September 25, 2019: Nature Communications
#14
JOURNAL ARTICLE
Elizabeth H Stover, Maria B Baco, Ofir Cohen, Yvonne Y Li, Elizabeth L Christie, Mukta Bagul, Amy Goodale, Yenarae Lee, Sasha Pantel, Matthew G Rees, Guo Wei, Adam G Presser, Maya K Gelbard, Weiqun Zhang, Ioannis K Zervantonakis, Patrick D Bhola, Jeremy Ryan, Jennifer L Guerriero, Joan Montero, Felice J Liang, Andrew D Cherniack, Federica Piccioni, Ursula A Matulonis, David D L Bowtell, Kristopher A Sarosiek, Anthony Letai, Levi A Garraway, Cory M Johannessen, Matthew Meyerson
High-grade serous ovarian cancer (HGSOC) is often sensitive to initial treatment with platinum and taxane combination chemotherapy, but most patients relapse with chemotherapy-resistant disease. To systematically identify genes modulating chemotherapy response, we performed pooled functional genomic screens in HGSOC cell lines treated with cisplatin, paclitaxel, or cisplatin plus paclitaxel. Genes in the intrinsic pathway of apoptosis were among the top candidate resistance genes in both gain-of-function and loss-of-function screens...
November 2019: Molecular Cancer Research: MCR
#15
JOURNAL ARTICLE
Haoxin Li, Maria Ericsson, Bokang Rabasha, Bogdan Budnik, Sze Ham Chan, Elizaveta Freinkman, Caroline A Lewis, John G Doench, Bridget K Wagner, Levi A Garraway, Stuart L Schreiber
The proteinaceous extracellular matrix (ECM) is vital for the survival, proliferation, migration, and differentiation of many types of cancer. However, little is known regarding metabolic pathways required for ECM secretion. By using an unbiased computational approach, we searched for enzymes whose suppression may lead to disruptions in protein secretion. Here, we show that 6-phosphogluconate dehydrogenase (PGD), a cytosolic enzyme involved in carbohydrate metabolism, is required for ER structural integrity and protein secretion...
September 19, 2019: Cell Chemical Biology
#16
JOURNAL ARTICLE
Ali Amin-Mansour, Suzanne George, Stefano Sioletic, Scott L Carter, Mara Rosenberg, Amaro Taylor-Weiner, Chip Stewart, Aaron Chevalier, Sara Seepo, Adam Tracy, Gad Getz, Jason L Hornick, Marisa R Nucci, Bradley Quade, George D Demetri, Chandrajit P Raut, Levi A Garraway, Eliezer M Van Allen, Andrew J Wagner
PURPOSE: Leiomyosarcoma and liposarcoma are common subtypes of soft tissue sarcoma (STS). Patients with metastatic leiomyosarcoma or dedifferentiated liposarcoma (DDLPS) typically have worse outcomes compared with localized leiomyosarcoma or well-differentiated liposarcoma (WDLPS). A better understanding of genetic changes between primary/metastatic leiomyosarcoma and between WDLPS/DDLPS may provide insight into their genetic evolution. EXPERIMENTAL DESIGN: We interrogated whole-exome sequencing (WES) from "trios" of normal tissue, primary tumor, and metastatic tumor from individual patients with leiomyosarcoma ( n = 9), and trios of normal tissue, well-differentiated tumor, and dedifferentiated tumor from individual patients with liposarcoma ( n = 19)...
August 15, 2019: Clinical Cancer Research
#17
JOURNAL ARTICLE
Haoxin Li, Shaoyang Ning, Mahmoud Ghandi, Gregory V Kryukov, Shuba Gopal, Amy Deik, Amanda Souza, Kerry Pierce, Paula Keskula, Desiree Hernandez, Julie Ann, Dojna Shkoza, Verena Apfel, Yilong Zou, Francisca Vazquez, Jordi Barretina, Raymond A Pagliarini, Giorgio G Galli, David E Root, William C Hahn, Aviad Tsherniak, Marios Giannakis, Stuart L Schreiber, Clary B Clish, Levi A Garraway, William R Sellers
Despite considerable efforts to identify cancer metabolic alterations that might unveil druggable vulnerabilities, systematic characterizations of metabolism as it relates to functional genomic features and associated dependencies remain uncommon. To further understand the metabolic diversity of cancer, we profiled 225 metabolites in 928 cell lines from more than 20 cancer types in the Cancer Cell Line Encyclopedia (CCLE) using liquid chromatography-mass spectrometry (LC-MS). This resource enables unbiased association analysis linking the cancer metabolome to genetic alterations, epigenetic features and gene dependencies...
May 2019: Nature Medicine
#18
JOURNAL ARTICLE
Mahmoud Ghandi, Franklin W Huang, Judit Jané-Valbuena, Gregory V Kryukov, Christopher C Lo, E Robert McDonald, Jordi Barretina, Ellen T Gelfand, Craig M Bielski, Haoxin Li, Kevin Hu, Alexander Y Andreev-Drakhlin, Jaegil Kim, Julian M Hess, Brian J Haas, François Aguet, Barbara A Weir, Michael V Rothberg, Brenton R Paolella, Michael S Lawrence, Rehan Akbani, Yiling Lu, Hong L Tiv, Prafulla C Gokhale, Antoine de Weck, Ali Amin Mansour, Coyin Oh, Juliann Shih, Kevin Hadi, Yanay Rosen, Jonathan Bistline, Kavitha Venkatesan, Anupama Reddy, Dmitriy Sonkin, Manway Liu, Joseph Lehar, Joshua M Korn, Dale A Porter, Michael D Jones, Javad Golji, Giordano Caponigro, Jordan E Taylor, Caitlin M Dunning, Amanda L Creech, Allison C Warren, James M McFarland, Mahdi Zamanighomi, Audrey Kauffmann, Nicolas Stransky, Marcin Imielinski, Yosef E Maruvka, Andrew D Cherniack, Aviad Tsherniak, Francisca Vazquez, Jacob D Jaffe, Andrew A Lane, David M Weinstock, Cory M Johannessen, Michael P Morrissey, Frank Stegmeier, Robert Schlegel, William C Hahn, Gad Getz, Gordon B Mills, Jesse S Boehm, Todd R Golub, Levi A Garraway, William R Sellers
Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities...
May 2019: Nature
#19
JOURNAL ARTICLE
Tikvah K Hayes, Flora Luo, Ofir Cohen, Amy B Goodale, Yenarae Lee, Sasha Pantel, Mukta Bagul, Federica Piccioni, David E Root, Levi A Garraway, Matthew Meyerson, Cory M Johannessen
Combinatorial inhibition of MEK1/2 and CDK4/6 is currently undergoing clinical investigation in NRAS-mutant melanoma. To prospectively map the landscape of resistance to this investigational regimen, we utilized a series of gain- and loss-of-function forward genetic screens to identify modulators of resistance to clinical inhibitors of MEK1/2 and CDK4/6 alone and in combination. First, we identified NRAS-mutant melanoma cell lines that were dependent on NRAS for proliferation and sensitive to MEK1/2 and CDK4/6 combination treatment...
May 1, 2019: Cancer Research
#20
JOURNAL ARTICLE
Ophélia Maertens, Ryan Kuzmickas, Haley E Manchester, Chloe E Emerson, Alessandra G Gavin, Caroline J Guild, Terence C Wong, Thomas De Raedt, Christian Bowman-Colin, Elodie Hatchi, Levi A Garraway, Keith T Flaherty, Shailja Pathania, Stephen J Elledge, Karen Cichowski
Although the majority of BRAF -mutant melanomas respond to BRAF/MEK inhibitors, these agents are not typically curative. Moreover, they are largely ineffective in NRAS - and NF1 -mutant tumors. Here we report that genetic and chemical suppression of HDAC3 potently cooperates with MAPK pathway inhibitors in all three RAS pathway-driven tumors. Specifically, we show that entinostat dramatically enhances tumor regression when combined with BRAF/MEK inhibitors, in both models that are sensitive or relatively resistant to these agents...
April 2019: Cancer Discovery
Make the most of Read.
Download the mobile app.
Download the mobile app.
Fetching more papers... 
