Intratumor Adoptive Transfer of IL-12 mRNA Transiently Engineered Antitumor CD8+ T Cells
Publication date: Available online 21 November 2019Source: Cancer CellAuthor(s): Iñaki Etxeberria, Elixabet Bolaños, Jose I. Quetglas, Alena Gros, Alberto Villanueva, Jara Palomero, Alfonso R. Sánchez-Paulete, Jose María Piulats, Xavier Matias-Guiu, Irene Olivera, Maria C. Ochoa, Sara Labiano, Saray Garasa, Inmaculada Rodriguez, August Vidal, Uxua Mancheño, Sandra Hervás-Stubbs, Arantza Azpilikueta, Itziar Otano, M. Angela AznarSummaryRetroviral gene transfer of interleukin-12 (IL-12) into T cells markedly enhances antitumor efficacy upon adoptive transfer but has clinically shown unacceptable severe side effects. T...
Source: Cancer Cell - November 23, 2019 Category: Cancer & Oncology Source Type: research
The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability
Publication date: Available online 14 November 2019Source: Cancer CellAuthor(s): Yun Huang, Brice Mouttet, Hans-Jörg Warnatz, Thomas Risch, Fabian Rietmann, Fabian Frommelt, Quy A. Ngo, Maria Pamela Dobay, Blerim Marovca, Silvia Jenni, Yi-Chien Tsai, Sören Matzk, Vyacheslav Amstislavskiy, Martin Schrappe, Martin Stanulla, Matthias Gstaiger, Beat Bornhauser, Marie-Laure Yaspo, Jean-Pierre BourquinSummaryThe chimeric transcription factor TCF3-HLF defines an incurable acute lymphoblastic leukemia subtype. Here we decipher the regulome of endogenous TCF3-HLF and dissect its essential transcriptional components and targets by...
Source: Cancer Cell - November 15, 2019 Category: Cancer & Oncology Source Type: research
Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors
Publication date: Available online 14 November 2019Source: Cancer CellAuthor(s): Parisa Mazrooei, Ken J. Kron, Yanyun Zhu, Stanley Zhou, Giacomo Grillo, Tahmid Mehdi, Musaddeque Ahmed, Tesa M. Severson, Paul Guilhamon, Nicholas Sinnott Armstrong, Vincent Huang, Takafumi N. Yamaguchi, Michael Fraser, Theodorus van der Kwast, Paul C. Boutros, Housheng Hansen He, Andries M. Bergman, Robert G. Bristow, Wilbert Zwart, Mathieu LupienSummaryThousands of noncoding somatic single-nucleotide variants (SNVs) of unknown function are reported in tumors. Partitioning the genome according to cistromes reveals the enrichment of somatic SN...
Source: Cancer Cell - November 15, 2019 Category: Cancer & Oncology Source Type: research
Inhibit versus Destroy: Are PROTAC Degraders the Solution to Targeting STAT3?
Publication date: 11 November 2019Source: Cancer Cell, Volume 36, Issue 5Author(s): Lisa N. Heppler, David A. FrankDespite the role of STAT3 as a known driver of oncogenesis, efforts to develop therapeutic STAT3 inhibitors have thus far been unsuccessful. In this issue of Cancer Cell, Bai et al. report a potent and selective STAT3 degrader capable of producing complete and long-lasting tumor regression in mouse xenograft models. (Source: Cancer Cell)
Source: Cancer Cell - November 12, 2019 Category: Cancer & Oncology Source Type: research
Induction of BRCAness in Triple-Negative Breast Cancer by a CDK12/13 Inhibitor Improves Chemotherapy
Publication date: 11 November 2019Source: Cancer Cell, Volume 36, Issue 5Author(s): Jessica L. Hopkins, Lee ZouIn this issue of Cancer Cell, Quereda and colleagues report that a newly developed specific inhibitor of CDK12/13, SR-4835, sensitizes triple-negative breast cancer cells to PARP inhibitors and DNA-damaging chemotherapeutics by reducing expression of the genes in the DNA damage response pathway. (Source: Cancer Cell)
Source: Cancer Cell - November 12, 2019 Category: Cancer & Oncology Source Type: research
Companion Diagnostics to Identify Biomarkers of Response to Anticancer Drugs Targeting the Proteome
Publication date: 11 November 2019Source: Cancer Cell, Volume 36, Issue 5Author(s): Anthony M. Joshua, Ian F. TannockIn this issue of Cancer Cell, Pillarsetty and colleagues radiolabel the potential anticancer drug PU-H71 and use it with PET imaging to quantify the epichaperome protein complex in tumors and its inhibition by the drug. They thereby develop a companion diagnostic paradigm of probe-drug pairing to explore therapeutic potential. (Source: Cancer Cell)
Source: Cancer Cell - November 12, 2019 Category: Cancer & Oncology Source Type: research
Tumor Neoantigens: When Too Much of a Good Thing Is Bad
Publication date: 11 November 2019Source: Cancer Cell, Volume 36, Issue 5Author(s): Anne Trinh, Kornelia PolyakImmunotherapy has been the most effective in tumors with high mutational burden. However, a recent study in Cell by Wolf et al. demonstrates that high intratumor heterogeneity (ITH) for cancer neoantigens paradoxically attenuates anti-tumor immune responses, suggesting a need to quantify ITH to improve patient selection for checkpoint blockade therapy. (Source: Cancer Cell)
Source: Cancer Cell - November 12, 2019 Category: Cancer & Oncology Source Type: research
Combination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors
Publication date: 11 November 2019Source: Cancer Cell, Volume 36, Issue 5Author(s): Rachel Grosser, Leonid Cherkassky, Navin Chintala, Prasad S. AdusumilliCheckpoint blockade (CPB) therapy can elicit durable clinical responses by reactivating an exhausted immune response. However, response rates remain limited, likely secondary to a lack of a tumor-reactive immune infiltrate. Chimeric antigen receptor (CAR) T cells may provide the necessary tumor-targeting immune infiltrate and a highly specific antitumor immune response. This can be further amplified by the addition of CPB agents, which serve to counteract the immune inh...
Source: Cancer Cell - November 12, 2019 Category: Cancer & Oncology Source Type: research
A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo
Publication date: 11 November 2019Source: Cancer Cell, Volume 36, Issue 5Author(s): Longchuan Bai, Haibin Zhou, Renqi Xu, Yujun Zhao, Krishnapriya Chinnaswamy, Donna McEachern, Jianyong Chen, Chao-Yie Yang, Zhaomin Liu, Mi Wang, Liu Liu, Hui Jiang, Bo Wen, Praveen Kumar, Jennifer L. Meagher, Duxin Sun, Jeanne A. Stuckey, Shaomeng WangSummarySignal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Here we report the discovery of SD-36, a small-molecule degrader of STAT3. SD-36 potently induces the degradation of STAT3 protein in vitro and in vivo and demonstrates high selectiv...
Source: Cancer Cell - November 12, 2019 Category: Cancer & Oncology Source Type: research
Stressing Out about Cancer Immunotherapy
Publication date: 11 November 2019Source: Cancer Cell, Volume 36, Issue 5Author(s): Xue-Yan He, David Ng, Linda Van Aelst, Mikala EgebladStress has long been suspected to negatively influence cancer mortality, yet the molecular mechanisms responsible for this effect have only recently been identified. A new study identifies a stress-induced response in dendritic cells—the activation of the glucocorticoid-inducible transcriptional regulator TSC22D3—as a potent, immunosuppressive effect of stress on cancer. (Source: Cancer Cell)
Source: Cancer Cell - November 12, 2019 Category: Cancer & Oncology Source Type: research
Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors
Publication date: Available online 7 November 2019Source: Cancer CellAuthor(s): Amaury Leruste, Jimena Tosello, Rodrigo Nalio Ramos, Arnault Tauziède-Espariat, Solène Brohard, Zhi-Yan Han, Kevin Beccaria, Mamy Andrianteranagna, Pamela Caudana, Jovan Nikolic, Céline Chauvin, Leticia Laura Niborski, Valeria Manriquez, Wilfrid Richer, Julien Masliah-Planchon, Sandrine Grossetête-Lalami, Mylene Bohec, Sonia Lameiras, Sylvain Baulande, Celio PouponnotSummaryRhabdoid tumors (RTs) are genomically simple pediatric cancers driven by the biallelic inactivation of SMARCB1, leading to SWI/SNF chromatin remodeler complex deficiency...
Source: Cancer Cell - November 8, 2019 Category: Cancer & Oncology Source Type: research
Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy
Publication date: Available online 31 October 2019Source: Cancer CellAuthor(s): Huiying Han, Atul D. Jain, Mihai I. Truica, Javier Izquierdo-Ferrer, Jonathan F. Anker, Barbara Lysy, Vinay Sagar, Yi Luan, Zachary R. Chalmers, Kenji Unno, Hanlin Mok, Rajita Vatapalli, Young A. Yoo, Yara Rodriguez, Irawati Kandela, J. Brandon Parker, Debabrata Chakravarti, Rama K. Mishra, Gary E. Schiltz, Sarki A. AbdulkadirSummarySmall molecules that directly target MYC and are also well tolerated in vivo will provide invaluable chemical probes and potential anti-cancer therapeutic agents. We developed a series of small-molecule MYC inhibit...
Source: Cancer Cell - November 2, 2019 Category: Cancer & Oncology Source Type: research
Therapeutic Targeting of CDK12/CDK13 in Triple-Negative Breast Cancer
Publication date: Available online 24 October 2019Source: Cancer CellAuthor(s): Victor Quereda, Simon Bayle, Francesca Vena, Sylvia M. Frydman, Andrii Monastyrskyi, William R. Roush, Derek R. DuckettSummaryEpigenetic regulation enables tumors to respond to changing environments during tumor progression and metastases and facilitates treatment resistance. Targeting chromatin modifiers or catalytic effectors of transcription is an emerging anti-cancer strategy. The cyclin-dependent kinases (CDKs) 12 and 13 phosphorylate the C-terminal domain of RNA polymerase II, regulating transcription and co-transcriptional processes. Her...
Source: Cancer Cell - October 25, 2019 Category: Cancer & Oncology Source Type: research
Paradigms for Precision Medicine in Epichaperome Cancer Therapy
Publication date: Available online 24 October 2019Source: Cancer CellAuthor(s): Nagavarakishore Pillarsetty, Komal Jhaveri, Tony Taldone, Eloisi Caldas-Lopes, Blesida Punzalan, Suhasini Joshi, Alexander Bolaender, Mohammad M. Uddin, Anna Rodina, Pengrong Yan, Anson Ku, Thomas Ku, Smit K. Shah, Serge Lyashchenko, Eva Burnazi, Tai Wang, Nicolas Lecomte, Yelena Janjigian, Anas Younes, Connie W. BatleviSummaryAlterations in protein-protein interaction networks are at the core of malignant transformation but have yet to be translated into appropriate diagnostic tools. We make use of the kinetic selectivity properties of an imag...
Source: Cancer Cell - October 25, 2019 Category: Cancer & Oncology Source Type: research
ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures
Publication date: Available online 17 October 2019Source: Cancer CellAuthor(s): Zulekha A. Qadeer, David Valle-Garcia, Dan Hasson, Zhen Sun, April Cook, Christie Nguyen, Aroa Soriano, Anqi Ma, Lyra M. Griffiths, Maged Zeineldin, Dan Filipescu, Luz Jubierre, Asif Chowdhury, Orla Deevy, Xiang Chen, David B. Finkelstein, Armita Bahrami, Elizabeth Stewart, Sara Federico, Soledad GallegoSummaryATRX alterations occur at high frequency in neuroblastoma of adolescents and young adults. Particularly intriguing are the large N-terminal deletions of ATRX (Alpha Thalassemia/Mental Retardation, X-linked) that generate in-frame fusion (...
Source: Cancer Cell - October 18, 2019 Category: Cancer & Oncology Source Type: research
