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Author William C. Hahn

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Haplotype-resolved germline and somatic alterations in renal medullary carcinomas.

Kar-Tong Tan, Hyunji Kim, Jian Carrot-Zhang, Yuxiang Zhang, Won Jun Kim, Guillaume Kugener, Jeremiah A Wala, Thomas P Howard, Yueh-Yun Chi, Rameen Beroukhim, Heng Li, Gavin Ha, Seth L Alper, Elizabeth J Perlman, Elizabeth A Mullen, William C Hahn, Matthew Meyerson, Andrew L Hong,

<h4>Background</h4>Renal medullary carcinomas (RMCs) are rare kidney cancers that occur in adolescents and young adults of African ancestry. Although RMC is associated with the sickle cell trait and somatic loss of the tumor suppressor, SMARCB1, the ancestral origins of RMC remain unknown. Further, characterization of structural variants (SVs) involving SMARCB1 ... Read more >>

Genome Med (Genome medicine)
[2021, 13(1):114]

Cited: 0 times

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Synthetic Lethal Interaction between the ESCRT Paralog Enzymes VPS4A and VPS4B in Cancers Harboring Loss of Chromosome 18q or 16q.

Jasper E Neggers, Brenton R Paolella, Adhana Asfaw, Michael V Rothberg, Thomas A Skipper, Annan Yang, Radha L Kalekar, John M Krill-Burger, Neekesh V Dharia, Guillaume Kugener, Jérémie Kalfon, Chen Yuan, Nancy Dumont, Alfredo Gonzalez, Mai Abdusamad, Yvonne Y Li, Liam F Spurr, Westley W Wu, Adam D Durbin, Brian M Wolpin, Federica Piccioni, David E Root, Jesse S Boehm, Andrew D Cherniack, Aviad Tsherniak, Andrew L Hong, William C Hahn, Kimberly Stegmaier, Todd R Golub, Francisca Vazquez, Andrew J Aguirre,

Cell Rep (Cell reports)
[2021, 36(2):109367]

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SMAD4 represses FOSL1 expression and pancreatic cancer metastatic colonization.

Chao Dai, Jonathan P Rennhack, Taylor E Arnoff, Maneesha Thaker, Scott T Younger, John G Doench, August Yue Huang, Annan Yang, Andrew J Aguirre, Belinda Wang, Evan Mun, Joyce T O'Connell, Ying Huang, Katherine Labella, Jessica A Talamas, Ji Li, Nina Ilic, Justin Hwang, Andrew L Hong, Andrew O Giacomelli, Ole Gjoerup, David E Root, William C Hahn,

Metastasis is a complex and poorly understood process. In pancreatic cancer, loss of the transforming growth factor (TGF)-β/BMP effector SMAD4 is correlated with changes in altered histopathological transitions, metastatic disease, and poor prognosis. In this study, we use isogenic cancer cell lines to identify SMAD4 regulated genes that contribute to ... Read more >>

Cell Rep (Cell reports)
[2021, 36(4):109443]

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Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer.

Sylvan C Baca, David Y Takeda, Ji-Heui Seo, Justin Hwang, Sheng Yu Ku, Rand Arafeh, Taylor Arnoff, Supreet Agarwal, Connor Bell, Edward O'Connor, Xintao Qiu, Sarah Abou Alaiwi, Rosario I Corona, Marcos A S Fonseca, Claudia Giambartolomei, Paloma Cejas, Klothilda Lim, Monica He, Anjali Sheahan, Amin Nassar, Jacob E Berchuck, Lisha Brown, Holly M Nguyen, Ilsa M Coleman, Arja Kaipainen, Navonil De Sarkar, Peter S Nelson, Colm Morrissey, Keegan Korthauer, Mark M Pomerantz, Leigh Ellis, Bogdan Pasaniuc, Kate Lawrenson, Kathleen Kelly, Amina Zoubeidi, William C Hahn, Himisha Beltran, Henry W Long, Myles Brown, Eva Corey, Matthew L Freedman,

Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism of adaptive resistance to targeted therapy in cancer. An archetypal example is the development of neuroendocrine prostate cancer (NEPC) after treatment of prostate adenocarcinoma (PRAD) with inhibitors of androgen signaling. NEPC is an aggressive ... Read more >>

Nat Commun (Nature communications)
[2021, 12(1):1979]

Cited: 2 times

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A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective.

Jason J Kwon, William C Hahn,

SHOC2 is a prototypical leucine-rich repeat protein that promotes downstream receptor tyrosine kinase (RTK)/RAS signaling and plays important roles in several cellular and developmental processes. Gain-of-function germ line mutations of SHOC2 drive the RASopathy Noonan-like syndrome, and SHOC2 mediates adaptive resistance to mitogen-activated protein kinase (MAPK) inhibitors. Similar to many ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(4):]

Cited: 0 times

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A first-generation pediatric cancer dependency map.

Neekesh V Dharia, Guillaume Kugener, Lillian M Guenther, Clare F Malone, Adam D Durbin, Andrew L Hong, Thomas P Howard, Pratiti Bandopadhayay, Caroline S Wechsler, Iris Fung, Allison C Warren, Joshua M Dempster, John M Krill-Burger, Brenton R Paolella, Phoebe Moh, Nishant Jha, Andrew Tang, Philip Montgomery, Jesse S Boehm, William C Hahn, Charles W M Roberts, James M McFarland, Aviad Tsherniak, Todd R Golub, Francisca Vazquez, Kimberly Stegmaier,

Exciting therapeutic targets are emerging from CRISPR-based screens of high mutational-burden adult cancers. A key question, however, is whether functional genomic approaches will yield new targets in pediatric cancers, known for remarkably few mutations, which often encode proteins considered challenging drug targets. To address this, we created a first-generation pediatric ... Read more >>

Nat Genet (Nature genetics)
[2021, 53(4):529-538]

Cited: 4 times

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Predicting cell health phenotypes using image-based morphology profiling.

Gregory P Way, Maria Kost-Alimova, Tsukasa Shibue, William F Harrington, Stanley Gill, Federica Piccioni, Tim Becker, Hamdah Shafqat-Abbasi, William C Hahn, Anne E Carpenter, Francisca Vazquez, Shantanu Singh,

Genetic and chemical perturbations impact diverse cellular phenotypes, including multiple indicators of cell health. These readouts reveal toxicity and antitumorigenic effects relevant to drug discovery and personalized medicine. We developed two customized microscopy assays, one using four targeted reagents and the other three targeted reagents, to collectively measure 70 specific ... Read more >>

Mol Biol Cell (Molecular biology of the cell)
[2021, 32(9):995-1005]

Cited: 2 times

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An expanded universe of cancer targets.

William C Hahn, Joel S Bader, Theodore P Braun, Andrea Califano, Paul A Clemons, Brian J Druker, Andrew J Ewald, Haian Fu, Subhashini Jagu, Christopher J Kemp, William Kim, Calvin J Kuo, Michael McManus, Gordon B Mills, Xiulei Mo, Nidhi Sahni, Stuart L Schreiber, Jessica A Talamas, Pablo Tamayo, Jeffrey W Tyner, Bridget K Wagner, William A Weiss, Daniela S Gerhard, ,

The characterization of cancer genomes has provided insight into somatically altered genes across tumors, transformed our understanding of cancer biology, and enabled tailoring of therapeutic strategies. However, the function of most cancer alleles remains mysterious, and many cancer features transcend their genomes. Consequently, tumor genomic characterization does not influence therapy ... Read more >>

Cell (Cell)
[2021, 184(5):1142-1155]

Cited: 10 times

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Global computational alignment of tumor and cell line transcriptional profiles.

Allison Warren, Yejia Chen, Andrew Jones, Tsukasa Shibue, William C Hahn, Jesse S Boehm, Francisca Vazquez, Aviad Tsherniak, James M McFarland,

Cell lines are key tools for preclinical cancer research, but it remains unclear how well they represent patient tumor samples. Direct comparisons of tumor and cell line transcriptional profiles are complicated by several factors, including the variable presence of normal cells in tumor samples. We thus develop an unsupervised alignment ... Read more >>

Nat Commun (Nature communications)
[2021, 12(1):22]

Cited: 5 times

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Rhabdoid Tumors Are Sensitive to the Protein-Translation Inhibitor Homoharringtonine.

Thomas P Howard, Elaine M Oberlick, Matthew G Rees, Taylor E Arnoff, Minh-Tam Pham, Lisa Brenan, Mariana DoCarmo, Andrew L Hong, Guillaume Kugener, Hsien-Chao Chou, Yiannis Drosos, Kaeli M Mathias, Pilar Ramos, Brinton Seashore-Ludlow, Andrew O Giacomelli, Xiaofeng Wang, Burgess B Freeman, Kaley Blankenship, Lauren Hoffmann, Hong L Tiv, Prafulla C Gokhale, Cory M Johannessen, Elizabeth A Stewart, Stuart L Schreiber, William C Hahn, Charles W M Roberts,

<h4>Purpose</h4>Rhabdoid tumors are devastating pediatric cancers in need of improved therapies. We sought to identify small molecules that exhibit <i>in vitro</i> and <i>in vivo</i> efficacy against preclinical models of rhabdoid tumor.<h4>Experimental design</h4>We screened eight rhabdoid tumor cell lines with 481 small molecules and compared their sensitivity with that of 879 ... Read more >>

Clin Cancer Res (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(18):4995-5006]

Cited: 0 times

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Selective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism.

Nathan J Schauer, Xiaoxi Liu, Robert S Magin, Laura M Doherty, Wai Cheung Chan, Scott B Ficarro, Wanyi Hu, Rebekka M Roberts, Roxana E Iacob, Björn Stolte, Andrew O Giacomelli, Sumner Perera, Kyle McKay, Sarah A Boswell, Ellen L Weisberg, Arghya Ray, Dharminder Chauhan, Sirano Dhe-Paganon, Ken C Anderson, James D Griffin, Jianing Li, William C Hahn, Peter K Sorger, John R Engen, Kimberly Stegmaier, Jarrod A Marto, Sara J Buhrlage,

Ubiquitin specific peptidase 7 (USP7) is a deubiquitinating enzyme (DUB) that removes ubiquitin tags from specific protein substrates in order to alter their degradation rate and sub-cellular localization. USP7 has been proposed as a therapeutic target in several cancers because it has many reported substrates with a role in cancer ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):5324]

Cited: 13 times

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ATM Loss Confers Greater Sensitivity to ATR Inhibition Than PARP Inhibition in Prostate Cancer.

Shahrzad Rafiei, Kenyon Fitzpatrick, David Liu, Mu-Yan Cai, Haitham A Elmarakeby, Jihye Park, Cora Ricker, Bose S Kochupurakkal, Atish D Choudhury, William C Hahn, Steven P Balk, Justin H Hwang, Eliezer M Van Allen, Kent W Mouw,

Alterations in DNA damage response (DDR) genes are common in advanced prostate tumors and are associated with unique genomic and clinical features. ATM is a DDR kinase that has a central role in coordinating DNA repair and cell-cycle response following DNA damage, and <i>ATM</i> alterations are present in approximately 5% ... Read more >>

Cancer Res (Cancer research)
[2020, 80(11):2094-2100]

Cited: 13 times

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Agreement between two large pan-cancer CRISPR-Cas9 gene dependency data sets.

Joshua M Dempster, Clare Pacini, Sasha Pantel, Fiona M Behan, Thomas Green, John Krill-Burger, Charlotte M Beaver, Scott T Younger, Victor Zhivich, Hanna Najgebauer, Felicity Allen, Emanuel Gonçalves, Rebecca Shepherd, John G Doench, Kosuke Yusa, Francisca Vazquez, Leopold Parts, Jesse S Boehm, Todd R Golub, William C Hahn, David E Root, Mathew J Garnett, Aviad Tsherniak, Francesco Iorio,

Genome-scale CRISPR-Cas9 viability screens performed in cancer cell lines provide a systematic approach to identify cancer dependencies and new therapeutic targets. As multiple large-scale screens become available, a formal assessment of the reproducibility of these experiments becomes necessary. We analyze data from recently published pan-cancer CRISPR-Cas9 screens performed at the ... Read more >>

Nat Commun (Nature communications)
[2019, 10(1):5817]

Cited: 33 times

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Author Correction: BRD9 defines a SWI/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors.

Xiaofeng Wang, Su Wang, Emma C Troisi, Thomas P Howard, Jeffrey R Haswell, Bennett K Wolf, William H Hawk, Pilar Ramos, Elaine M Oberlick, Evgeni P Tzvetkov, Aaron Ross, Francisca Vazquez, William C Hahn, Peter J Park, Charles W M Roberts,

An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Read more >>

Nat Commun (Nature communications)
[2019, 10(1):4445]

Cited: 0 times

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Small-Molecule and CRISPR Screening Converge to Reveal Receptor Tyrosine Kinase Dependencies in Pediatric Rhabdoid Tumors.

Elaine M Oberlick, Matthew G Rees, Brinton Seashore-Ludlow, Francisca Vazquez, Geoffrey M Nelson, Neekesh V Dharia, Barbara A Weir, Aviad Tsherniak, Mahmoud Ghandi, John M Krill-Burger, Robin M Meyers, Xiaofeng Wang, Phil Montgomery, David E Root, Jake M Bieber, Sandi Radko, Jaime H Cheah, C Suk-Yee Hon, Alykhan F Shamji, Paul A Clemons, Peter J Park, Michael A Dyer, Todd R Golub, Kimberly Stegmaier, William C Hahn, Elizabeth A Stewart, Stuart L Schreiber, Charles W M Roberts,

Cancer is often seen as a disease of mutations and chromosomal abnormalities. However, some cancers, including pediatric rhabdoid tumors (RTs), lack recurrent alterations targetable by current drugs and need alternative, informed therapeutic options. To nominate potential targets, we performed a high-throughput small-molecule screen complemented by a genome-scale CRISPR-Cas9 gene-knockout screen ... Read more >>

Cell Rep (Cell reports)
[2019, 28(9):2331-2344.e8]

Cited: 10 times

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A dominant-negative effect drives selection of TP53 missense mutations in myeloid malignancies.

Steffen Boettcher, Peter G Miller, Rohan Sharma, Marie McConkey, Matthew Leventhal, Andrei V Krivtsov, Andrew O Giacomelli, Waihay Wong, Jesi Kim, Sherry Chao, Kari J Kurppa, Xiaoping Yang, Kirsten Milenkowic, Federica Piccioni, David E Root, Frank G Rücker, Yael Flamand, Donna Neuberg, R Coleman Lindsley, Pasi A Jänne, William C Hahn, Tyler Jacks, Hartmut Döhner, Scott A Armstrong, Benjamin L Ebert,

<i>TP53</i>, which encodes the tumor suppressor p53, is the most frequently mutated gene in human cancer. The selective pressures shaping its mutational spectrum, dominated by missense mutations, are enigmatic, and neomorphic gain-of-function (GOF) activities have been implicated. We used CRISPR-Cas9 to generate isogenic human leukemia cell lines of the most ... Read more >>

Science (Science (New York, N.Y.))
[2019, 365(6453):599-604]

Cited: 57 times

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Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers.

Rita Sulahian, Jason J Kwon, Katherine H Walsh, Emma Pailler, Timothy L Bosse, Maneesha Thaker, Diego Almanza, Joshua M Dempster, Joshua Pan, Federica Piccioni, Nancy Dumont, Alfredo Gonzalez, Jonathan Rennhack, Behnam Nabet, John A Bachman, Amy Goodale, Yenarae Lee, Mukta Bagul, Rosy Liao, Adrija Navarro, Tina L Yuan, Raymond W S Ng, Srivatsan Raghavan, Nathanael S Gray, Aviad Tsherniak, Francisca Vazquez, David E Root, Ari J Firestone, Jeff Settleman, William C Hahn, Andrew J Aguirre,

The mitogen-activated protein kinase (MAPK) pathway is a critical effector of oncogenic RAS signaling, and MAPK pathway inhibition may be an effective combination treatment strategy. We performed genome-scale loss-of-function CRISPR-Cas9 screens in the presence of a MEK1/2 inhibitor (MEKi) in KRAS-mutant pancreatic and lung cancer cell lines and identified genes ... Read more >>

Cell Rep (Cell reports)
[2019, 29(1):118-134.e8]

Cited: 13 times

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Neuronal differentiation and cell-cycle programs mediate response to BET-bromodomain inhibition in MYC-driven medulloblastoma.

Pratiti Bandopadhayay, Federica Piccioni, Ryan O'Rourke, Patricia Ho, Elizabeth M Gonzalez, Graham Buchan, Kenin Qian, Gabrielle Gionet, Emily Girard, Margo Coxon, Matthew G Rees, Lisa Brenan, Frank Dubois, Ofer Shapira, Noah F Greenwald, Melanie Pages, Amanda Balboni Iniguez, Brenton R Paolella, Alice Meng, Claire Sinai, Giovanni Roti, Neekesh V Dharia, Amanda Creech, Benjamin Tanenbaum, Prasidda Khadka, Adam Tracy, Hong L Tiv, Andrew L Hong, Shannon Coy, Rumana Rashid, Jia-Ren Lin, Glenn S Cowley, Fred C Lam, Amy Goodale, Yenarae Lee, Kathleen Schoolcraft, Francisca Vazquez, William C Hahn, Aviad Tsherniak, James E Bradner, Michael B Yaffe, Till Milde, Stefan M Pfister, Jun Qi, Monica Schenone, Steven A Carr, Keith L Ligon, Mark W Kieran, Sandro Santagata, James M Olson, Prafulla C Gokhale, Jacob D Jaffe, David E Root, Kimberly Stegmaier, Cory M Johannessen, Rameen Beroukhim,

BET-bromodomain inhibition (BETi) has shown pre-clinical promise for MYC-amplified medulloblastoma. However, the mechanisms for its action, and ultimately for resistance, have not been fully defined. Here, using a combination of expression profiling, genome-scale CRISPR/Cas9-mediated loss of function and ORF/cDNA driven rescue screens, and cell-based models of spontaneous resistance, we identify ... Read more >>

Nat Commun (Nature communications)
[2019, 10(1):2400]

Cited: 11 times

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TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma.

Lipika Goyal, Lei Shi, Leah Y Liu, Ferran Fece de la Cruz, Jochen K Lennerz, Srivatsan Raghavan, Ignaty Leschiner, Liudmila Elagina, Giulia Siravegna, Raymond W S Ng, Phuong Vu, Krushna C Patra, Supriya K Saha, Raul N Uppot, Ron Arellano, Stephanie Reyes, Takeshi Sagara, Sachie Otsuki, Brandon Nadres, Heather A Shahzade, Ipsita Dey-Guha, Isobel J Fetter, Islam Baiev, Emily E Van Seventer, Janet E Murphy, Cristina R Ferrone, Kenneth K Tanabe, Vikram Deshpande, James J Harding, Rona Yaeger, Robin K Kelley, Alberto Bardelli, A John Iafrate, William C Hahn, Cyril H Benes, David T Ting, Hiroshi Hirai, Gad Getz, Dejan Juric, Andrew X Zhu, Ryan B Corcoran, Nabeel Bardeesy,

ATP-competitive fibroblast growth factor receptor (FGFR) kinase inhibitors, including BGJ398 and Debio 1347, show antitumor activity in patients with intrahepatic cholangiocarcinoma (ICC) harboring activating FGFR2 gene fusions. Unfortunately, acquired resistance develops and is often associated with the emergence of secondary FGFR2 kinase domain mutations. Here, we report that the irreversible ... Read more >>

Cancer Discov (Cancer discovery)
[2019, 9(8):1064-1079]

Cited: 54 times

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Next-generation characterization of the Cancer Cell Line Encyclopedia.

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 ... Read more >>

Nature (Nature)
[2019, 569(7757):503-508]

Cited: 437 times

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BRD9 defines a SWI/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors.

Xiaofeng Wang, Su Wang, Emma C Troisi, Thomas P Howard, Jeffrey R Haswell, Bennett K Wolf, William H Hawk, Pilar Ramos, Elaine M Oberlick, Evgeni P Tzvetkov, Aaron Ross, Francisca Vazquez, William C Hahn, Peter J Park, Charles W M Roberts,

Bromodomain-containing protein 9 (BRD9) is a recently identified subunit of SWI/SNF(BAF) chromatin remodeling complexes, yet its function is poorly understood. Here, using a genome-wide CRISPR-Cas9 screen, we show that BRD9 is a specific vulnerability in pediatric malignant rhabdoid tumors (RTs), which are driven by inactivation of the SMARCB1 subunit of ... Read more >>

Nat Commun (Nature communications)
[2019, 10(1):1881]

Cited: 32 times

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MDM2 and MDM4 Are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors.

Thomas P Howard, Taylor E Arnoff, Melinda R Song, Andrew O Giacomelli, Xiaofeng Wang, Andrew L Hong, Neekesh V Dharia, Su Wang, Francisca Vazquez, Minh-Tam Pham, Ann M Morgan, Franziska Wachter, Gregory H Bird, Guillaume Kugener, Elaine M Oberlick, Matthew G Rees, Hong L Tiv, Justin H Hwang, Katherine H Walsh, April Cook, John M Krill-Burger, Aviad Tsherniak, Prafulla C Gokhale, Peter J Park, Kimberly Stegmaier, Loren D Walensky, William C Hahn, Charles W M Roberts,

Malignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. In this study, we screened several MRT cell lines with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries to identify potential drug targets specific for these cancers. We discovered <i>MDM2</i> and <i>MDM4</i>, the canonical negative regulators of ... Read more >>

Cancer Res (Cancer research)
[2019, 79(9):2404-2414]

Cited: 10 times

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MCL1 and DEDD Promote Urothelial Carcinoma Progression.

Andrew L Hong, Jennifer L Guerriero, Mihir B Doshi, Bryan D Kynnap, Won Jun Kim, Anna C Schinzel, Rebecca Modiste, Amy J Schlauch, Rosalyn M Adam, David J Kwiatkowski, Rameen Beroukhim, Anthony Letai, Jonathan E Rosenberg, William C Hahn,

Focal amplification of chromosome 1q23.3 in patients with advanced primary or relapsed urothelial carcinomas is associated with poor survival. We interrogated chromosome 1q23.3 and the nearby focal amplicon 1q21.3, as both are associated with increased lymph node disease in patients with urothelial carcinoma. Specifically, we assessed whether the oncogene <i>MCL1</i> ... Read more >>

Mol Cancer Res (Molecular cancer research : MCR)
[2019, 17(6):1294-1304]

Cited: 1 time

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Small-molecule targeting of brachyury transcription factor addiction in chordoma.

Tanaz Sharifnia, Mathias J Wawer, Ting Chen, Qing-Yuan Huang, Barbara A Weir, Ann Sizemore, Matthew A Lawlor, Amy Goodale, Glenn S Cowley, Francisca Vazquez, Christopher J Ott, Joshua M Francis, Slim Sassi, Patricia Cogswell, Hadley E Sheppard, Tinghu Zhang, Nathanael S Gray, Paul A Clarke, Julian Blagg, Paul Workman, Josh Sommer, Francis Hornicek, David E Root, William C Hahn, James E Bradner, Kwok K Wong, Paul A Clemons, Charles Y Lin, Joanne D Kotz, Stuart L Schreiber,

Chordoma is a primary bone cancer with no approved therapy<sup>1</sup>. The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in chordoma tumors<sup>2,3</sup>. Here we describe the discovery of therapeutically targetable chordoma dependencies via genome-scale CRISPR-Cas9 screening and focused ... Read more >>

Nat Med (Nature medicine)
[2019, 25(2):292-300]

Cited: 23 times

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Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells.

Hugh S Gannon, Tao Zou, Michael K Kiessling, Galen F Gao, Diana Cai, Peter S Choi, Alexandru P Ivan, Ilana Buchumenski, Ashton C Berger, Jonathan T Goldstein, Andrew D Cherniack, Francisca Vazquez, Aviad Tsherniak, Erez Y Levanon, William C Hahn, Matthew Meyerson,

Systematic exploration of cancer cell vulnerabilities can inform the development of novel cancer therapeutics. Here, through analysis of genome-scale loss-of-function datasets, we identify adenosine deaminase acting on RNA (ADAR or ADAR1) as an essential gene for the survival of a subset of cancer cell lines. ADAR1-dependent cell lines display increased ... Read more >>

Nat Commun (Nature communications)
[2018, 9(1):5450]

Cited: 47 times

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