MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition

Horiuchi, Dai; Kusdra, Leonard; Huskey, Noelle E.; Chandriani, Sanjay; Lenburg, Marc E.; Gonzalez-Angulo, Ana Maria; Creasman, Katelyn J.; Bazarov, Alexey V.; Smyth, James W.; Davis, Sarah E.; Yaswen, Paul; Mills, Gordon B.; Esserman, Laura J.; Goga, Andrei

doi:10.1084/jem.20111512

MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition

Journal Article · Mon Mar 19 00:00:00 EDT 2012 · Journal of Experimental Medicine

DOI:https://doi.org/10.1084/jem.20111512· OSTI ID:1625196

Horiuchi, Dai ^[1]; Kusdra, Leonard ^[2]; Huskey, Noelle E. ^[2]; Chandriani, Sanjay ^[2]; Lenburg, Marc E. ^[3]; Gonzalez-Angulo, Ana Maria ^[4]; Creasman, Katelyn J. ^[2]; Bazarov, Alexey V. ^[5]; Smyth, James W. ^[2]; Davis, Sarah E. ^[6]; Yaswen, Paul ^[7]; Mills, Gordon B. ^[8]; Esserman, Laura J. ^[9]; Goga, Andrei ^[10]

University of California, San Francisco, CA (United States); DOE/OSTI
University of California, San Francisco, CA (United States)
Boston University, MA (United States)
M.D. Anderson Cancer Center, Houston, TX (United States)
University of California, San Francisco, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Univ. of California, San Francisco, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
M.D. Anderson Cancer Center, Houston, TX (United States). Dept of Breast Medical Oncology and Systems Biology
Univ. of California, San Francisco, CA (United States). Dept. of Surgery; Univ. of California, San Francisco, CA (United States). Helen Diller Family Comprehensive Cancer Center
Univ. of California, San Francisco, CA (United States). Dept. of Medicine; Univ. of California, San Francisco, CA (United States). Helen Diller Family Comprehensive Cancer Center

Estrogen, progesterone, and HER2 receptor-negative triple-negative breast cancers encompass the most clinically challenging subtype for which targeted therapeutics are lacking. We find that triple-negative tumors exhibit elevated MYC expression, as well as altered expression of MYC regulatory genes, resulting in increased activity of the MYC pathway. In primary breast tumors, MYC signaling did not predict response to neoadjuvant chemotherapy but was associated with poor prognosis. We exploit the increased MYC expression found in triple-negative breast cancers by using a synthetic-lethal approach dependent on cyclin-dependent kinase (CDK) inhibition. CDK inhibition effectively induced tumor regression in triple-negative tumor xenografts. The proapoptotic BCL-2 family member BIM is up-regulated after CDK inhibition and contributes to this synthetic-lethal mechanism. These results indicate that aggressive breast tumors with elevated MYC are uniquely sensitive to CDK inhibitors.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: California Breast Cancer Research Program; Howard Hughes Medical Institute; Susan G. Komen Foundation; UC Cancer Coordinating Committee; USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1625196

Journal Information:: Journal of Experimental Medicine, Journal Name: Journal of Experimental Medicine Journal Issue: 4 Vol. 209; ISSN 0022-1007

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Triple-Negative Breast Cancer and the Need for New Therapeutic Targets Engebraaten, Olav; Vollan, Hans Kristian Moen; Børresen-Dale, Anne-Lise The American Journal of Pathology, Vol. 183, Issue 4 https://doi.org/10.1016/j.ajpath.2013.05.033	journal	October 2013
A pan-cancer proteomic perspective on The Cancer Genome Atlas Akbani, Rehan; Ng, Patrick Kwok Shing; Werner, Henrica M. J. Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4887	journal	May 2014
Erratum: Meta-analysis of the global gene expression profile of triple-negative breast cancer identifies genes for the prognostication and treatment of aggressive breast cancer Al-Ejeh, F.; Simpson, P. T.; Saunus, J. M. Oncogenesis, Vol. 3, Issue 10 https://doi.org/10.1038/oncsis.2014.41	journal	October 2014
Inhibition of the integrin/FAK signaling axis and c-Myc synergistically disrupts ovarian cancer malignancy Xu, B.; Lefringhouse, J.; Liu, Z. Oncogenesis, Vol. 6, Issue 1 https://doi.org/10.1038/oncsis.2016.86	journal	January 2017
G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer Dragan, Magdalena; Nguyen, Mai-Uyen; Guzman, Stephania Cell Death & Disease, Vol. 11, Issue 2 https://doi.org/10.1038/s41419-020-2305-7	journal	February 2020
Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27 García-Gutiérrez, Lucía; Bretones, Gabriel; Molina, Ester Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-54917-1	journal	December 2019
Inflammatory signaling in genomically instable cancers Talens, Francien; Van Vugt, Marcel A. T. M. Cell Cycle, Vol. 18, Issue 16 https://doi.org/10.1080/15384101.2019.1638192	journal	July 2019
Mutation Profiling of Key Cancer Genes in Primary Breast Cancers and Their Distant Metastases Schrijver, Willemijne A. M. E.; Selenica, Pier; Lee, Ju Youn Cancer Research, Vol. 78, Issue 12 https://doi.org/10.1158/0008-5472.can-17-2310	journal	June 2018
An integrated bioinformatics analysis to dissect kinase dependency in triple negative breast cancer Ryall, Karen A.; Kim, Jihye; Klauck, Peter J. BMC Genomics, Vol. 16, Issue S12 https://doi.org/10.1186/1471-2164-16-s12-s2	journal	December 2015
Wnt modulates MCL1 to control cell survival in triple negative breast cancer Yang, Lixin; Perez, Aldwin Apollo; Fujie, Sayuri BMC Cancer, Vol. 14, Issue 1 https://doi.org/10.1186/1471-2407-14-124	journal	February 2014
Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells Bilir, Birdal; Kucuk, Omer; Moreno, Carlos S. Journal of Translational Medicine, Vol. 11, Issue 1 https://doi.org/10.1186/1479-5876-11-280	journal	November 2013
MYC amplification in subtypes of breast cancers in African American women Naab, Tammey J.; Gautam, Anita; Ricks-Santi, Luisel BMC Cancer, Vol. 18, Issue 1 https://doi.org/10.1186/s12885-018-4171-6	journal	March 2018
Midostaurin preferentially attenuates proliferation of triple-negative breast cancer cell lines through inhibition of Aurora kinase family Kawai, Masaaki; Nakashima, Akio; Kamada, Shinji Journal of Biomedical Science, Vol. 22, Issue 1 https://doi.org/10.1186/s12929-015-0150-2	journal	July 2015
Identification of Chemical Inhibitors of β-Catenin-Driven Liver Tumorigenesis in Zebrafish Evason, Kimberley J.; Francisco, Macrina T.; Juric, Vladislava PLOS Genetics, Vol. 11, Issue 7 https://doi.org/10.1371/journal.pgen.1005305	journal	July 2015
Taking on Challenging Targets: Making MYC Druggable Horiuchi, Dai; Anderton, Brittany; Goga, Andrei American Society of Clinical Oncology Educational Book, Issue 34 https://doi.org/10.14694/edbook_am.2014.34.e497	journal	May 2014
Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors Vaughan, Lynsey; Clarke, Paul A.; Barker, Karen Oncotarget, Vol. 7, Issue 36 https://doi.org/10.18632/oncotarget.10544	journal	July 2016
Inhibition of cyclin dependent kinase 9 by dinaciclib suppresses cyclin B1 expression and tumor growth in triple negative breast cancer Rajput, Sandeep; Khera, Nimmish; Guo, Zhanfang Oncotarget, Vol. 7, Issue 35 https://doi.org/10.18632/oncotarget.10870	journal	July 2016
The bromodomain inhibitor OTX015 (MK-8628) exerts anti-tumor activity in triple-negative breast cancer models as single agent and in combination with everolimus Vázquez, Ramiro; Riveiro, María E.; Astorgues-Xerri, Lucile Oncotarget, Vol. 8, Issue 5 https://doi.org/10.18632/oncotarget.13814	journal	December 2016
High Myc expression and transcription activity underlies intra-tumoral heterogeneity in triple-negative breast cancer Gupta, Nidhi; Jung, Karen; Wu, Chengsheng Oncotarget, Vol. 8, Issue 17 https://doi.org/10.18632/oncotarget.15891	journal	March 2017
Synergistic effect of eribulin and CDK inhibition for the treatment of triple negative breast cancer Rao, Shreyas S.; Stoehr, Jenna; Dokic, Danijela Oncotarget, Vol. 8, Issue 48 https://doi.org/10.18632/oncotarget.20202	journal	August 2017
Antineoplastic effects of selective CDK9 inhibition with atuveciclib on cancer stem-like cells in triple-negative breast cancer Brisard, Daphne; Eckerdt, Frank; Marsh, Lindsey A. Oncotarget, Vol. 9, Issue 99 https://doi.org/10.18632/oncotarget.26468	journal	December 2018
Sensitivity to cdk1-inhibition is modulated by p53 status in preclinical models of embryonal tumors Schwermer, Melanie; Lee, Sangkyun; Köster, Johannes Oncotarget, Vol. 6, Issue 17 https://doi.org/10.18632/oncotarget.3908	journal	May 2015
In vivo Reprogramming of Cancer Metabolism by MYC Camarda, Roman; Williams, Jeremy; Goga, Andrei Frontiers in Cell and Developmental Biology, Vol. 5 https://doi.org/10.3389/fcell.2017.00035	journal	April 2017
MYC and AMPK–Save Energy or Die! Haikala, Heidi M.; Anttila, Johanna M.; Klefström, Juha Frontiers in Cell and Developmental Biology, Vol. 5 https://doi.org/10.3389/fcell.2017.00038	journal	April 2017
Characterization of Frequently Mutated Cancer Genes and Tumor Mutation Burden in Chinese Breast Cancer Xiao, Weikai; Zhang, Guochun; Chen, Bo Frontiers in Oncology, Vol. 11 https://doi.org/10.3389/fonc.2021.618767	journal	April 2021
Racial Disparity and Triple-Negative Breast Cancer in African-American Women: A Multifaceted Affair between Obesity, Biology, and Socioeconomic Determinants Siddharth, Sumit; Sharma, Dipali Cancers, Vol. 10, Issue 12 https://doi.org/10.3390/cancers10120514	journal	December 2018
Cancer’s Achilles’ Heel: Apoptosis and Necroptosis to the Rescue Dasgupta, Atreyi; Nomura, Motonari; Shuck, Ryan International Journal of Molecular Sciences, Vol. 18, Issue 1 https://doi.org/10.3390/ijms18010023	journal	December 2016
High MYC mRNA Expression Is More Clinically Relevant than MYC DNA Amplification in Triple-Negative Breast Cancer Katsuta, Eriko; Yan, Li; Takeshita, Takashi International Journal of Molecular Sciences, Vol. 21, Issue 1 https://doi.org/10.3390/ijms21010217	journal	December 2019
A Pipeline for Integrated Theory and Data-Driven Modeling of Genomic and Clinical Data Raghu, Vineet K.; Ge, Xiaoyu; Balajee, Arun arXiv https://doi.org/10.48550/arxiv.2005.02521	preprint	January 2020
Additional file 2 of Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer Jian, Yunting; Huang, Xinjian; Fang, Lishan figshare https://doi.org/10.6084/m9.figshare.13719318.v1	image	January 2021
Additional file 3 of Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer Jian, Yunting; Huang, Xinjian; Fang, Lishan figshare https://doi.org/10.6084/m9.figshare.13719321.v1	image	January 2021
Additional file 4 of Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer Jian, Yunting; Huang, Xinjian; Fang, Lishan figshare https://doi.org/10.6084/m9.figshare.13719324.v1	image	January 2021
Additional file 5 of Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer Jian, Yunting; Huang, Xinjian; Fang, Lishan figshare https://doi.org/10.6084/m9.figshare.13719327	image	January 2021
Additional file 6 of Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer Jian, Yunting; Huang, Xinjian; Fang, Lishan figshare https://doi.org/10.6084/m9.figshare.13719330.v1	image	January 2021
Additional file 7 of Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer Jian, Yunting; Huang, Xinjian; Fang, Lishan figshare https://doi.org/10.6084/m9.figshare.13719333	image	January 2021
Additional file 8 of Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer Jian, Yunting; Huang, Xinjian; Fang, Lishan figshare https://doi.org/10.6084/m9.figshare.13719336	image	January 2021
Additional file 9 of Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer Jian, Yunting; Huang, Xinjian; Fang, Lishan figshare https://doi.org/10.6084/m9.figshare.13719339.v1	image	January 2021
Targeting MYC in cancer therapy: RNA processing offers new opportunities Koh, Cheryl M.; Sabò, Arianna; Guccione, Ernesto BioEssays, Vol. 38, Issue 3 https://doi.org/10.1002/bies.201500134	journal	January 2016
Targeted next-generation sequencing enables reliable detection of HER2 (ERBB2) status in breast cancer and provides ancillary information of clinical relevance: NGS-BASED DETECTION OF HER2 STATUS Pfarr, Nicole; Penzel, Roland; Endris, Volker Genes, Chromosomes and Cancer, Vol. 56, Issue 4 https://doi.org/10.1002/gcc.22431	journal	November 2016
Integrated network analysis and machine learning approach for the identification of key genes of triple‐negative breast cancer Naorem, Leimarembi Devi; Muthaiyan, Mathavan; Venkatesan, Amouda Journal of Cellular Biochemistry, Vol. 120, Issue 4 https://doi.org/10.1002/jcb.27903	journal	October 2018
The key genes underlying pathophysiology association between the type 2‐diabetic and colorectal cancer Peng, Wen‐Fang; Bai, Feng; Shao, Kan Journal of Cellular Physiology, Vol. 233, Issue 11 https://doi.org/10.1002/jcp.26440	journal	June 2018
Identification of dysregulated miRNAs in triple negative breast cancer: A meta‐analysis approach Naorem, Leimarembi Devi; Muthaiyan, Mathavan; Venkatesan, Amouda Journal of Cellular Physiology, Vol. 234, Issue 7 https://doi.org/10.1002/jcp.27839	journal	November 2018
An overview of triple-negative breast cancer Kumar, Pankaj; Aggarwal, Rupali Archives of Gynecology and Obstetrics, Vol. 293, Issue 2 https://doi.org/10.1007/s00404-015-3859-y	journal	September 2015
Comprehensive genomic profiling of inflammatory breast cancer cases reveals a high frequency of clinically relevant genomic alterations Ross, Jeffrey S.; Ali, Siraj M.; Wang, Kai Breast Cancer Research and Treatment, Vol. 154, Issue 1 https://doi.org/10.1007/s10549-015-3592-z	journal	October 2015
Inhibiting CDK in Cancer Therapy: Current Evidence and Future Directions Vijayaraghavan, Smruthi; Moulder, Stacy; Keyomarsi, Khandan Targeted Oncology, Vol. 13, Issue 1 https://doi.org/10.1007/s11523-017-0541-2	journal	December 2017
Mission Possible: Advances in MYC Therapeutic Targeting in Cancer Allen-Petersen, Brittany L.; Sears, Rosalie C. BioDrugs, Vol. 33, Issue 5 https://doi.org/10.1007/s40259-019-00370-5	journal	August 2019
Protein phosphatase 2A activation as a therapeutic strategy for managing MYC-driven cancers Farrington, Caroline C.; Yuan, Eric; Mazhar, Sahar Journal of Biological Chemistry, Vol. 295, Issue 3 https://doi.org/10.1016/s0021-9258(17)49933-9	journal	January 2020
Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles Walz, Susanne; Lorenzin, Francesca; Morton, Jennifer Nature, Vol. 511, Issue 7510 https://doi.org/10.1038/nature13473	journal	July 2014
Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells Lawson, Devon A.; Bhakta, Nirav R.; Kessenbrock, Kai Nature, Vol. 526, Issue 7571 https://doi.org/10.1038/nature15260	journal	September 2015
The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy Lukey, Michael J.; Greene, Kai Su; Erickson, Jon W. Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms11321	journal	April 2016
Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer Camarda, Roman; Zhou, Alicia Y.; Kohnz, Rebecca A. Nature Medicine, Vol. 22, Issue 4 https://doi.org/10.1038/nm.4055	journal	March 2016
PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer Brasó-Maristany, Fara; Filosto, Simone; Catchpole, Steven Nature Medicine, Vol. 22, Issue 11 https://doi.org/10.1038/nm.4198	journal	October 2016
Cell cycle proteins as promising targets in cancer therapy Otto, Tobias; Sicinski, Piotr Nature Reviews Cancer, Vol. 17, Issue 2 https://doi.org/10.1038/nrc.2016.138	journal	January 2017
Emerging targeted agents in metastatic breast cancer Zardavas, Dimitrios; Baselga, José; Piccart, Martine Nature Reviews Clinical Oncology, Vol. 10, Issue 4 https://doi.org/10.1038/nrclinonc.2013.29	journal	March 2013
Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease Bianchini, Giampaolo; Balko, Justin M.; Mayer, Ingrid A. Nature Reviews Clinical Oncology, Vol. 13, Issue 11 https://doi.org/10.1038/nrclinonc.2016.66	journal	May 2016
CDK/CK1 inhibitors roscovitine and CR8 downregulate amplified MYCN in neuroblastoma cells Delehouzé, C.; Godl, K.; Loaëc, N. Oncogene, Vol. 33, Issue 50 https://doi.org/10.1038/onc.2013.513	journal	December 2013
Tumor penetrating peptides inhibiting MYC as a potent targeted therapeutic strategy for triple-negative breast cancers Wang, Edina; Sorolla, Anabel; Cunningham, Paula T. Oncogene, Vol. 38, Issue 1 https://doi.org/10.1038/s41388-018-0421-y	journal	August 2018
Comparative oncogenomics identifies combinations of driver genes and drug targets in BRCA1-mutated breast cancer Annunziato, Stefano; de Ruiter, Julian R.; Henneman, Linda Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-08301-2	journal	January 2019
Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy Haikala, Heidi M.; Anttila, Johanna M.; Marques, Elsa Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-08541-2	journal	February 2019
Metabolic reprogramming in triple-negative breast cancer through Myc suppression of TXNIP Shen, Liangliang; O’Shea, John M.; Kaadige, Mohan R. Proceedings of the National Academy of Sciences, Vol. 112, Issue 17 https://doi.org/10.1073/pnas.1501555112	journal	April 2015
Mechanistic Aspects of Folded Protein Transport by the Twin Arginine Translocase (Tat) Cline, Kenneth Journal of Biological Chemistry, Vol. 290, Issue 27 https://doi.org/10.1074/jbc.r114.626820	journal	May 2015
Protein phosphatase 2A activation as a therapeutic strategy for managing MYC-driven cancers Farrington, Caroline C.; Yuan, Eric; Mazhar, Sahar Journal of Biological Chemistry, Vol. 295, Issue 3 https://doi.org/10.1074/jbc.ra119.011443	journal	December 2019
Inhibition of CDK-mediated Smad3 phosphorylation reduces the Pin1-Smad3 interaction and aggressiveness of triple negative breast cancer cells Thomas, Alexandra L.; Lind, Hanne; Hong, Angela Cell Cycle, Vol. 16, Issue 15 https://doi.org/10.1080/15384101.2017.1338988	journal	July 2017
Intratumor heterogeneity predicts metastasis of triple-negative breast cancer Yang, Fang; Wang, Yucai; Li, Quan Carcinogenesis, Vol. 38, Issue 9 https://doi.org/10.1093/carcin/bgx071	journal	July 2017
MYC Dysregulates Mitotic Spindle Function Creating a Dependency on TPX2 Rohrberg, Julia; Corella, Alexandra; Taileb, Moufida BioRxiv https://doi.org/10.1101/272336	posted_content	January 2018
Tumor cell-adipocyte gap junctions activate lipolysis and are essential for breast tumorigenesis Camarda, Roman; Williams, Jeremy; Malkov, Serghei BioRxiv https://doi.org/10.1101/277939	posted_content	January 2018
Metabolomic profiling of mouse mammary tumor derived cell lines reveals targeted therapy options for cancer subtypes Ogrodzinski, Martin P.; Lunt, Sophia Y. Cellular Oncology https://doi.org/10.1101/796573	journal	January 2019
Targeting MYCN-expressing triple-negative breast cancer with BET and MEK inhibitors Schafer, Johanna M.; Lehmann, Brian D.; Gonzalez-Ericsson, Paula I. Science Translational Medicine, Vol. 12, Issue 534 https://doi.org/10.1126/scitranslmed.aaw8275	journal	March 2020
Molecular Markers for Breast Cancer: Prediction on Tumor Behavior Banin Hirata, Bruna Karina; Oda, Julie Massayo Maeda; Losi Guembarovski, Roberta Disease Markers, Vol. 2014 https://doi.org/10.1155/2014/513158	journal	January 2014
Dinaciclib induces immunogenic cell death and enhances anti-PD1–mediated tumor suppression Hossain, Dewan Md Sakib; Javaid, Sarah; Cai, Mingmei Journal of Clinical Investigation, Vol. 128, Issue 2 https://doi.org/10.1172/jci94586	journal	January 2018
Pharmacological targeting of MYC-regulated IRE1/XBP1 pathway suppresses MYC-driven breast cancer Zhao, Na; Cao, Jin; Xu, Longyong Journal of Clinical Investigation, Vol. 128, Issue 4 https://doi.org/10.1172/jci95873	journal	February 2018
Featured Article: Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells Huang, Ou; Zhang, Weili; Zhi, Qiaoming Experimental Biology and Medicine, Vol. 240, Issue 4 https://doi.org/10.1177/1535370214554881	journal	October 2014
Therapeutic vulnerability of multiple myeloma to MIR17PTi, a first-in-class inhibitor of pri-miR-17-92 Morelli, Eugenio; Biamonte, Lavinia; Federico, Cinzia Blood, Vol. 132, Issue 10 https://doi.org/10.1182/blood-2018-03-836601	journal	September 2018
Targeting cyclin-dependent kinase 1 (CDK1) but not CDK4/6 or CDK2 is selectively lethal to MYC-dependent human breast cancer cells Kang, Jian; Sergio, C. Marcelo; Sutherland, Robert L. BMC Cancer, Vol. 14, Issue 1 https://doi.org/10.1186/1471-2407-14-32	journal	January 2014
Myc is required for β-catenin-mediated mammary stem cell amplification and tumorigenesis Moumen, Mejdi; Chiche, Aurélie; Decraene, Charles Molecular Cancer, Vol. 12, Issue 1 https://doi.org/10.1186/1476-4598-12-132	journal	October 2013
Highly robust model of transcription regulator activity predicts breast cancer overall survival Dong, Chuanpeng; Liu, Jiannan; Chen, Steven X. BMC Medical Genomics, Vol. 13, Issue S5 https://doi.org/10.1186/s12920-020-0688-z	journal	April 2020
Applications of patient-derived tumor xenograft models and tumor organoids Yoshida, Go J. Journal of Hematology & Oncology, Vol. 13, Issue 1 https://doi.org/10.1186/s13045-019-0829-z	journal	January 2020
Combination therapy with protein kinase inhibitor H89 and Tetrandrine elicits enhanced synergistic antitumor efficacy Yu, Man; Liu, Ting; Chen, Yicheng Journal of Experimental & Clinical Cancer Research, Vol. 37, Issue 1 https://doi.org/10.1186/s13046-018-0779-2	journal	June 2018
Integrated omics-based pathway analyses uncover CYP epoxygenase-associated networks as theranostic targets for metastatic triple negative breast cancer Apaya, Maria Karmella; Shiau, Jeng-Yuan; Liao, Guo-Shiou Journal of Experimental & Clinical Cancer Research, Vol. 38, Issue 1 https://doi.org/10.1186/s13046-019-1187-y	journal	May 2019
Inferring synthetic lethal interactions from mutual exclusivity of genetic events in cancer Srihari, Sriganesh; Singla, Jitin; Wong, Limsoon Biology Direct, Vol. 10, Issue 1 https://doi.org/10.1186/s13062-015-0086-1	journal	October 2015
Human transposons are an abundant supply of transcription factor binding sites and promoter activities in breast cancer cell lines Jiang, Jiayue-Clara; Upton, Kyle R. Mobile DNA, Vol. 10, Issue 1 https://doi.org/10.1186/s13100-019-0158-3	journal	April 2019
CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours Costa-Cabral, Sara; Brough, Rachel; Konde, Asha PLOS ONE, Vol. 11, Issue 2 https://doi.org/10.1371/journal.pone.0149099	journal	February 2016
Cyclin-dependent kinase inhibitors closer to market launch? Galons, Hervé; Oumata, Nassima; Gloulou, Olfa Expert Opinion on Therapeutic Patents, Vol. 23, Issue 8 https://doi.org/10.1517/13543776.2013.789861	journal	April 2013
Triple negative breast cancer chemosensitivity and chemoresistance: current advances in biomarkers indentification Guestini, Fouzia; McNamara, Keely May; Ishida, Takanori Expert Opinion on Therapeutic Targets, Vol. 20, Issue 6 https://doi.org/10.1517/14728222.2016.1125469	journal	December 2015
PIM Kinase as an Executional Target in Cancer Zhang, Xinning; Song, Mengqiu; Kundu, Joydeb Kumar Journal of Cancer Prevention, Vol. 23, Issue 3 https://doi.org/10.15430/jcp.2018.23.3.109	journal	September 2018
MYC Dysregulates Mitotic Spindle Function Creating a Dependency on TPX2 Rohrberg, Julia; Corella, Alexandra; Taileb, Moufida SSRN Electronic Journal https://doi.org/10.2139/ssrn.3189389	journal	January 2018
MYC-Driven Pathways in Breast Cancer Subtypes Fallah, Yassi; Brundage, Janetta; Allegakoen, Paul Biomolecules, Vol. 7, Issue 4 https://doi.org/10.3390/biom7030053	journal	July 2017
Targeting Cancer Stem Cells in Triple-Negative Breast Cancer Park, So-Yeon; Choi, Jang-Hyun; Nam, Jeong-Seok Cancers, Vol. 11, Issue 7, p. 965 https://doi.org/10.3390/cancers11070965	journal	July 2019
The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs Brown, Justin M.; Wasson, Marie-Claire D.; Marcato, Paola Cells, Vol. 9, Issue 3 https://doi.org/10.3390/cells9030763	journal	March 2020
MYC Oncogene Contributions to Release of Cell Cycle Brakes García-Gutiérrez, Lucía; Delgado, María Dolores; León, Javier Genes, Vol. 10, Issue 3 https://doi.org/10.3390/genes10030244	journal	March 2019
Inferring synthetic lethal interactions from mutual exclusivity of genetic events in cancer Srihari, Sriganesh; Singla, Jitin; Wong, Limsoon arXiv https://doi.org/10.48550/arxiv.1510.00815	text	January 2015

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