Measuring, Modeling, and Controlling Heterogeneity Center for Cancer Systems Biology (M2CH)
What is the M2CH?
The Measuring, Modeling and Controlling Heterogeneity Center for Cancer Systems Biology (M2CH-CCSB, or simply M2CH), is one of thirteen "U54 Research Centers" which are part of the Research Network of the National Cancer Institute Cancer Systems Biology Consortium.
Goal is to improve management of triple negative breast cancer
Our overall goal at the M2CH Center for Cancer Systems Biology is to improve management of triple negative breast cancer by preventing cancer cells from developing resistance to chemotherapy. We are looking at how both intrinsic and extrinsic factors shape the ability of cancer cells to become resistant to cancer drugs. Intrinsic factors include DNA modifications, or epigenetic features of cancer cells. Extrinsic factors include molecular signals in the immediate environment, or microenvironment of cancer cells.
A cancer systems biology approach to breast cancer
We learn how intrinsic and extrinsic factors influence differentiation state, proliferation and therapeutic response in triple negative breast cancer through experimental manipulation and computational modeling of cancer cell lines, 3D-engineered multicellular systems, xenografts and clinical specimens. We deploy single cell omic and imaging technologies that allow quantitative assessment of molecular, cellular, and structural heterogeneity. We interpret these data using computational models that define control networks and structures in heterogeneous systems as well as transitions between states of therapeutic resistance and sensitivity.
This is accomplished in three related projects:
- Project 1 focuses on measuring and managing resistance-associated heterogeneity intrinsic to cancer cells.
- Project 2 focuses on identifying resistance-associated signals from the microenvironment and on mitigating effects from these signals on therapeutic response.
- Project 3 applies spatial systems biology approaches to triple negative breast cancer specimens and multicell type models thereof to discover molecular control networks that influence how cell intrinsic plasticity and microenvironment signaling alter therapeutic responses in complex tissues. All Projects analyze core cell lines, patient derived cultures, and FDA approved, pathway-targeted drugs (afatinib, ruxolotinib, trametinib, BYL719, cabozantinib, and everolimus).
Learn more about M2CH and each of its three projects at the Cancer Systems Biology Consortium site.
Contact
Please direct any inquiries regarding the Measuring, Modeling and Controlling Heterogeneity (M2CH) Center to Heidi Feiler, Scientific Program Manager, feiler@ohsu.edu.
Publications
- MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms. Erdem C, Gross SM, Heiser LM, Birtwistle MR.Nat Commun. 2023 Jul 6;14(1):3991. doi: 10.1038/s41467-023-39729-2. PubMed PMID: 37414767. PubMed Central PMCID: PMC10326020
- Gross SM, Mohammadi F, Sanchez-Aguila C, Zhan PJ, Liby TA, Dane MA, Meyer AS, Heiser LM. Analysis and modeling of cancer drug responses using cell cycle phase-specific rate effects. Nat Commun. 2023 Jun 10;14(1):3450. doi: 10.1038/s41467-023-39122-z. PubMed PMID: 37301933; PubMed Central PMCID: PMC10257663.
- Copperman J, Gross SM, Chang YH, Heiser LM, Zuckerman DM. Morphodynamical cell state description via live-cell imaging trajectory embedding. Commun Biol. 2023;6(1):484. Epub 20230504. doi: 10.1038/s42003-023-04837-8. PubMed PMID: 37142678; PubMed Central PMCID: PMC10160022.
- Tatarova Z, Blumberg DC, Bensen A, Mills GB, Jonas O. Panobinostat Induced Spatial In Situ Biomarkers Predictive of Anti-PD-1 Efficacy in Mouse Mammary Carcinoma. Cells. 2023 Jan 13;12(2):308. doi: 10.3390/cells12020308. PMID: 36672243; PMCID: PMC9856407.
- Kim H, Wirasaputra A, Mohammadi F, Kundu AN, Esteves JAE, Heiser LM, Meyer AS, Peyton SR. Live Cell Lineage Tracing of Dormant Cancer Cells. Adv Healthc Mater. 2023 Jan 10:e2202275. doi: 10.1002/adhm.202202275. Epub ahead of print. PMID: 36625629.
- M. P. Chapman, R. Bonalli, K. M. Smith, I. Yang, M. Pavone and C. J. Tomlin, "Risk-Sensitive Safety Analysis Using Conditional Value-at-Risk," in IEEE Transactions on Automatic Control, vol. 67, no. 12, pp. 6521-6536, Dec. 2022, doi: 10.1109/TAC.2021.3131149.
- Shree Bose; Barroso M, Chheda MG, Clevers H, Elez E, Kaochar S, Kopetz SE, Li XN, Meric-Bernstam F, Meyer CA, Mou H, Naegle KM, Pera MF, Perova Z, Politi KA, Raphael BJ, Robson P, Sears RC, Tabernero J, Tuveson DA, Welm AL, Welm BE, Willey CD, Salnikow K, Chuang JH, Shen X. A path to translation: How 3D patient tumor avatars enable next generation precision oncology. Cancer Cell. 2022 Dec 12;40(12):1448-1453. doi: 10.1016/j.ccell.2022.09.017. Epub 2022 Oct 20. PMID: 36270276.
- Mohammadi F, Visagan S, Gross SM, Karginov L, Lagarde JC, Heiser LM, Meyer AS. A lineage tree-based hidden Markov model quantifies cellular heterogeneity and plasticity. Commun Biol. 2022 Nov 17;5(1):1258. doi: 10.1038/s42003-022-04208-9. PMID: 36396800; PMCID: PMC9671968.
- Hunt GJ, Dane MA, Korkola JE, Heiser LM, Gagnon-Bartsch JA. Systematic replication enables normalization of high-throughput imaging assays. Bioinformatics. 2022 Oct 31;38(21):4934-4940. doi: 10.1093/bioinformatics/btac606. PMID: 36063034; PMCID: PMC9620822.
- Sofia D, Mohammad Mirzaei N, Shahriyari L. Patient-Specific Mathematical Model of the Clear Cell Renal Cell Carcinoma Microenvironment. J Pers Med. 2022 Oct 9;12(10):1681. doi: 10.3390/jpm12101681. PMID: 36294824; PMCID: PMC9605269.
- Moser R, Annis J, Nikolova O, Whatcott C, Gurley K, Mendez E, Moran-Jones K, Dorrell C, Sears RC, Kuo C, Han H, Biankin A, Grandori C, Von Hoff DD, Kemp CJ. Pharmacologic Targeting of TFIIH Suppresses KRAS-Mutant Pancreatic Ductal Adenocarcinoma and Synergizes with TRAIL. Cancer Res. 2022 Sep 16;82(18):3375-3393. doi: 10.1158/0008-5472.CAN-21-4222. PMID: 35819261; PMCID: PMC9481717.
- Ternes L, Lin JR, Chen YA, Gray JW, Chang YH. Computational multiplex panel reduction to maximize information retention in breast cancer tissue microarrays. PLoS Comput Biol. 2022 Sep 30;18(9):e1010505. doi: 10.1371/journal.pcbi.1010505. PMID: 36178966; PMCID: PMC9555662.
- Phelps C, Huang T, Wang J, Nan X. Multipair Förster Resonance Energy Transfer via Spectrally Resolved Single-Molecule Detection. J Phys Chem B. 2022 Aug 11;126(31):5765-5771. doi: 10.1021/acs.jpcb.2c03249. Epub 2022 Jul 27. PMID: 35897122; PMCID: PMC9377335.
- Koester AM, Tao K, Szczepaniak M, Rames MJ, Nan X. Nanoscopic Spatial Association between Ras and Phosphatidylserine on the Cell Membrane Studied with Multicolor Super Resolution Microscopy. Biomolecules. 2022 Jul 26;12(8):1033. doi: 10.3390/biom12081033. PMID: 35892343; PMCID: PMC9332490.
- Daniel CJ, Pelz C, Wang X, Munks MW, Ko A, Murugan D, Byers SA, Juarez E, Taylor KL, Fan G, Coussens LM, Link JM, Sears RC. T-cell Dysfunction upon Expression of MYC with Altered Phosphorylation at Threonine 58 and Serine 62. Mol Cancer Res. 2022 Jul 6;20(7):1151-1165. doi: 10.1158/1541-7786.MCR-21-0560. PMID: 35380701; PMCID: PMC9262837.
- Tatarova Z, Blumberg DC, Korkola JE, Heiser LM, Muschler JL, Schedin PJ, Ahn SW, Mills GB, Coussens LM, Jonas O, Gray JW. A multiplex implantable microdevice assay identifies synergistic combinations of cancer immunotherapies and conventional drugs. Nat Biotechnol. 2022 Jul 4. doi: 10.1038/s41587-022-01379-y. Epub ahead of print. PMID: 35788566.
- Erdem C, Mutsuddy A, Bensman EM, Dodd WB, Saint-Antoine MM, Bouhaddou M, Blake RC, Gross SM, Heiser LM, Feltus FA, Birtwistle MR. A scalable, open-source implementation of a large-scale mechanistic model for single cell proliferation and death signaling. Nat Commun. 2022 Jun 21;13(1):3555. doi: 10.1038/s41467-022-31138-1. PMID: 35729113; PMCID: PMC9213456.
- Sundaram S, Kim EN, Jones GM, Sivagnanam S, Tripathi M, Miremadi A, Di Pietro M, Coussens LM, Fitzgerald RC, Chang YH, Zhuang L. Deciphering the Immune Complexity in Esophageal Adenocarcinoma and Pre-Cancerous Lesions With Sequential Multiplex Immunohistochemistry and Sparse Subspace Clustering Approach. Front Immunol. 2022 May 19;13:874255. doi: 10.3389/fimmu.2022.874255. PMID: 35663986; PMCID: PMC9161782.
- Mohammad Mirzaei N, Tatarova Z, Hao W, Changizi N, Asadpoure A, Zervantonakis IK, Hu Y, Chang YH, Shahriyari L. A PDE Model of Breast Tumor Progression in MMTV-PyMT Mice. J Pers Med. 2022 May 17;12(5):807. doi: 10.3390/jpm12050807. PMID: 35629230; PMCID: PMC9145520.
- Eng J, Bucher E, Hu Z, Zheng T, Gibbs SL, Chin K, Gray JW. A framework for multiplex imaging optimization and reproducible analysis. Commun Biol. 2022 May 11;5(1):438. doi: 10.1038/s42003-022-03368-y. PMID: 35545666; PMCID: PMC9095647.
- Ternes L, Dane M, Gross S, Labrie M, Mills G, Gray J, Heiser L, Chang YH. A multi-encoder variational autoencoder controls multiple transformational features in single-cell image analysis. Commun Biol. 2022 Mar 23;5(1):255. doi: 10.1038/s42003-022-03218-x. PMID: 35322205; PMCID: PMC8943013.
- Mohammad Mirzaei N, Changizi N, Asadpoure A, Su S, Sofia D, Tatarova Z, Zervantonakis IK, Chang YH, Shahriyari L. Investigating key cell types and molecules dynamics in PyMT mice model of breast cancer through a mathematical model. PLoS Comput Biol. 2022 Mar 16;18(3):e1009953. doi: 10.1371/journal.pcbi.1009953. PMID: 35294447; PMCID: PMC8959189.
- Liu M, Smith R, Liby T, Chiotti K, López CS, Korkola JE. INHBA is a mediator of aggressive tumor behavior in HER2+ basal breast cancer. Breast Cancer Res. 2022 Mar 5;24(1):18. doi: 10.1186/s13058-022-01512-4. PMID: 35248133; PMCID: PMC8898494.
- Ozdemir ES, Koester AM, Nan X. Ras Multimers on the Membrane: Many Ways for a Heart-to-Heart Conversation. Genes. 2022;13(2):219. PubMed PMID: doi:10.3390/genes13020219.
- Johnson BE, Creason AL, Stommel JM, Keck JM, Parmar S, Betts CB, Blucher A, Boniface C, Bucher E, Burlingame E, Camp T, Chin K, Eng J, Estabrook J, Feiler HS, Heskett MB, Hu Z, Kolodzie A, Kong BL, Labrie M, Lee J, Leyshock P, Mitri S, Patterson J, Riesterer JL, Sivagnanam S, Somers J, Sudar D, Thibault G, Weeder BR, Zheng C, Nan X, Thompson RF, Heiser LM, Spellman PT, Thomas G, Demir E, Chang YH, Coussens LM, Guimaraes AR, Corless C, Goecks J, Bergan R, Mitri Z, Mills GB, Gray JW. An omic and multidimensional spatial atlas from serial biopsies of an evolving metastatic breast cancer. Cell Rep Med. 2022 Feb 15;3(2):100525. doi: 10.1016/j.xcrm.2022.100525. PMID: 35243422; PMCID: PMC8861971.
- Goltsev Y, White BS, Tyson DR, Sokolov A. A community-based approach to image analysis of cells, tissues and tumors. Comput Med Imaging Graph. 2022 Jan;95:102013. doi: 10.1016/j.compmedimag.2021.102013. Epub 2021 Nov 19. PMID: 34864359; PMCID: PMC8761177.
- Mulqueen RM, Pokholok D, O'Connell BL, Thornton CA, Zhang F, O'Roak BJ, Link J, Yardımcı GG, Sears RC, Steemers FJ, Adey AC. High-content single-cell combinatorial indexing. Nat Biotechnol. 2021 Dec;39(12):1574-1580. doi: 10.1038/s41587-021-00962-z. Epub 2021 Jul 5. PMID: 34226710; PMCID: PMC8678206.
- Hammer, M., Huisman, M., Rigano, A. et al. Towards community-driven metadata standards for light microscopy: tiered specifications extending the OME model. Nat Methods 18, 1427–1440 (2021). https://doi.org/10.1038/s41592-021-01327-9
- Labrie M, Li A, Creason A, Betts C, Keck J, Johnson B, Sivagnanam S, Boniface C, Ma H, Blucher A, Chang YH, Chin K, Vuky J, Guimaraes AR, Downey M, Lim JY, Gao L, Siex K, Parmar S, Kolodzie A, Spellman PT, Goecks J, Coussens LM, Corless CL, Bergan R, Gray JW, Mills GB, Mitri ZI. Multiomics analysis of serial PARP inhibitor treated metastatic TNBC inform on rational combination therapies. NPJ Precis Oncol. 2021 Oct 19;5(1):92. doi: 10.1038/s41698-021-00232-w. PMID: 34667258; PMCID: PMC8526613.
- Nelson G, Boehm U, Bagley S, Bajcsy P, Bischof J, Brown CM, Dauphin A, Dobbie IM, Eriksson JE, Faklaris O, Fernandez-Rodriguez J, Ferrand A, Gelman L, Gheisari A, Hartmann H, Kukat C, Laude A, Mitkovski M, Munck S, North AJ, Rasse TM, Resch-Genger U, Schuetz LC, Seitz A, Strambio-De-Castillia C, Swedlow JR, Alexopoulos I, Aumayr K, Avilov S, Bakker GJ, Bammann RR, Bassi A, Beckert H, Beer S, Belyaev Y, Bierwagen J, Birngruber KA, Bosch M, Breitlow J, Cameron LA, Chalfoun J, Chambers JJ, Chen CL, Conde-Sousa E, Corbett AD, Cordelieres FP, Nery ED, Dietzel R, Eismann F, Fazeli E, Felscher A, Fried H, Gaudreault N, Goh WI, Guilbert T, Hadleigh R, Hemmerich P, Holst GA, Itano MS, Jaffe CB, Jambor HK, Jarvis SC, Keppler A, Kirchenbuechler D, Kirchner M, Kobayashi N, Krens G, Kunis S, Lacoste J, Marcello M, Martins GG, Metcalf DJ, Mitchell CA, Moore J, Mueller T, Nelson MS, Ogg S, Onami S, Palmer AL, Paul-Gilloteaux P, Pimentel JA, Plantard L, Podder S, Rexhepaj E, Royon A, Saari MA, Schapman D, Schoonderwoert V, Schroth-Diez B, Schwartz S, Shaw M, Spitaler M, Stoeckl MT, Sudar D, Teillon J, Terjung S, Thuenauer R, Wilms CD, Wright GD, Nitschke R. QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy. J Microsc. 2021 Oct;284(1):56-73. doi: 10.1111/jmi.13041. Epub 2021 Aug 11. PMID: 34214188.
- Zheng F, Kelly MR, Ramms DJ, Heintschel ML, Tao K, Tutuncuoglu B, Lee JJ, Ono K, Foussard H, Chen M, Herrington KA, Silva E, Liu SN, Chen J, Churas C, Wilson N, Kratz A, Pillich RT, Patel DN, Park J, Kuenzi B, Yu MK, Licon K, Pratt D, Kreisberg JF, Kim M, Swaney DL, Nan X, Fraley SI, Gutkind JS, Krogan NJ, Ideker T. Interpretation of cancer mutations using a multiscale map of protein systems. Science. 2021 Oct;374(6563):eabf3067. doi: 10.1126/science.abf3067. Epub 2021 Oct 1. PMID: 34591613.
- Gross SM, Mohammadi F, Sanchez-Aguila C, Zhan PJ, Meyer AS, Heiser LM. Analysis and modeling of cancer drug responses using cell cycle phase-specific rate effects. bioRxiv. doi: https://doi.org/10.1101/2020.07.24.219907
- Burlingame EA, Eng J, Thibault G, Chin K, Gray JW, Chang YH. Toward reproducible, scalable, and robust data analysis across multiplex tissue imaging platforms. Cell Rep Methods. 2021 Aug 23;1(4):100053. doi: 10.1016/j.crmeth.2021.100053. Epub 2021 Jul 23. PMID: 34485971; PMCID: PMC8415641.
- Liefwalker DF, Ryan M, Wang Z, Pathak KV, Plaisier S, Shah V, Babra B, Dewson GS, Lai IK, Mosley AR, Fueger PT, Casey SC, Jiang L, Pirrotte P, Swaminathan S, Sears RC. Metabolic convergence on lipogenesis in RAS, BCR-ABL, and MYC-driven lymphoid malignancies. Cancer Metab. 2021 Aug 16;9(1):31. doi: 10.1186/s40170-021-00263-8. PMID: 34399819; PMCID: PMC8369789.
- Garay, J.P., Smith, R., Devlin, K. et al. Sensitivity to targeted therapy differs between HER2-amplified breast cancer cells harboring kinase and helical domain mutations in PIK3CA. Breast Cancer Res 23, 81 (2021). https://doi.org/10.1186/s13058-021-01457-0
- Dietz MS, Sutton TL, Walker BS, Gast CE, Zarour L, Sengupta SK, Swain JR, Eng J, Parappilly M, Limbach K, Sattler A, Burlingame E, Chin Y, Gower A, Mira JLM, Sapre A, Chiu YJ, Clayburgh DR, Pommier SJ, Cetnar JP, Fischer JM, Jaboin JJ, Pommier RF, Sheppard BC, Tsikitis VL, Skalet AH, Mayo SC, Lopez CD, Gray JW, Mills GB, Mitri Z, Chang YH, Chin K, Wong MH. Relevance of circulating hybrid cells as a non-invasive biomarker for myriad solid tumors. Sci Rep. 2021 Jul 1;11(1):13630. doi: 10.1038/s41598-021-93053-7. PMID: 34211050; PMCID: PMC8249418.
- Janiszewska M, Stein S, Metzger Filho O, Eng J, Kingston NL, Harper NW, Rye IH, Alečković M, Trinh A, Murphy KC, Marangoni E, Cristea S, Oakes B, Winer EP, Krop IE, Russnes HG, Spellman PT, Bucher E, Hu Z, Chin K, Gray JW, Michor F, Polyak K. The impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2+ breast cancer. JCI Insight. 2021 Jun 8;6(11):e147617. doi: 10.1172/jci.insight.147617. PMID: 33886505; PMCID: PMC8262355.
- Di Leo L, Bodemeyer V, Bosisio FM, Claps G, Carretta M, Rizza S, Faienza F, Frias A, Khan S, Bordi M, Pacheco MP, Di Martino J, Bravo-Cordero JJ, Daniel CJ, Sears RC, Donia M, Madsen DH, Guldberg P, Filomeni G, Sauter T, Robert C, De Zio D, Cecconi F. Loss of Ambra1 promotes melanoma growth and invasion. Nat Commun. 2021 May 5;12(1):2550. doi: 10.1038/s41467-021-22772-2. PMID: 33953176; PMCID: PMC8100102.
- Daniel CJ, Sun XX, Chen Y, Zhang X, Dai MS, Sears RC. Detection of Post-translational Modifications on MYC. Methods Mol Biol. 2021;2318:69-85. doi: 10.1007/978-1-0716-1476-1_5. PMID: 34019287.
- Mohammadi F, Visagan S, Gross SM, Karginov L, Lagarde J, Heiser LM, Meyer AS. A lineage tree-based hidden Markov model to quantify cellular heterogeneity and plasticity. bioRxiv. 2021:2021.06.25.449922. doi: 10.1101/2021.06.25.449922.
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- Maiani E, Milletti G, Nazio F, Holdgaard SG, Bartkova J, Rizza S, Cianfanelli V, Lorente M, Simoneschi D, Di Marco M, D'Acunzo P, Di Leo L, Rasmussen R, Montagna C, Raciti M, De Stefanis C, Gabicagogeascoa E, Rona G, Salvador N, Pupo E, Merchut-Maya JM, Daniel CJ, Carinci M, Cesarini V, O'sullivan A, Jeong YT, Bordi M, Russo F, Campello S, Gallo A, Filomeni G, Lanzetti L, Sears RC, Hamerlik P, Bartolazzi A, Hynds RE, Pearce DR, Swanton C, Pagano M, Velasco G, Papaleo E, De Zio D, Maya-Mendoza A, Locatelli F, Bartek J, Cecconi F. AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. Nature. 2021 Apr;592(7856):799-803. doi: 10.1038/s41586-021-03422-5. Epub 2021 Apr 14. PMID: 33854232; PMCID: PMC8864551.
- Ghodsi Asnaashari T., Chang Y.H. (2021) Strategies to Reduce Long-Term Drug Resistance by Considering Effects of Differential Selective Treatments. In: Bebis G., Gaasterland T., Kato M., Kohandel M., Wilkie K. (eds) Mathematical and Computational Oncology. ISMCO 2021. Lecture Notes in Computer Science, vol 13060. Springer, Cham. https://doi.org/10.1007/978-3-030-91241-3_5
- CSBC/PS-ON Image Analysis Working Group, Vizcarra JC, Burlingame EA, Hug CB, Goltsev Y, White BS, Tyson DR, Sokolov A. A community-based approach to image analysis of cells, tissues and tumors. Comput Med Imaging Graph. 2022 Jan;95:102013. doi: 10.1016/j.compmedimag.2021.102013. Epub 2021 Nov 19. PMID: 34864359; PMCID: PMC8761177.
- Mohammad Mirzaei N, Su S, Sofia D, Hegarty M, Abdel-Rahman MH, Asadpoure A, Cebulla CM, Chang YH, Hao W, Jackson PR, Lee AV, Stover DG, Tatarova Z, Zervantonakis IK, Shahriyari L. A Mathematical Model of Breast Tumor Progression Based on Immune Infiltration. J Pers Med. 2021 Oct 15;11(10):1031. doi: 10.3390/jpm11101031. PMID: 34683171; PMCID: PMC8540934.
- Burlingame EA, Eng J, Thibault G, Chin K, Gray JW, Chang YH. Toward reproducible, scalable, and robust data analysis across multiplex tissue imaging platforms. Cell Reports Methods. 2021;1(4):100053. doi: https://doi.org/10.1016/j.crmeth.2021.100053.
- Dietz, M.S., Sutton, T.L., Walker, B.S. et al. Relevance of circulating hybrid cells as a non-invasive biomarker for myriad solid tumors. Sci Rep 11, 13630 (2021). https://doi.org/10.1038/s41598-021-93053-7
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- Grzadkowski MR, Holly HD, Somers J, Demir E. Systematic interrogation of mutation groupings reveals divergent downstream expression programs within key cancer genes. BMC Bioinformatics. 2021 May 6;22(1):233. doi: 10.1186/s12859-021-04147-y. PMID: 33957863; PMCID: PMC8101181.
- Babur Ö, Luna A, Korkut A, Durupinar F, Siper MC, Dogrusoz U, Vaca Jacome AS, Peckner R, Christianson KE, Jaffe JD, Spellman PT, Aslan JE, Sander C, Demir E. Causal interactions from proteomic profiles: Molecular data meet pathway knowledge. Patterns (N Y). 2021 May 12;2(6):100257. doi: 10.1016/j.patter.2021.100257. PMID: 34179843; PMCID: PMC8212145.
- Tognon CE, Sears RC, Mills GB, Gray JW, Tyner JW. Ex Vivo Analysis of Primary Tumor Specimens for Evaluation of Cancer Therapeutics. Annu Rev Cancer Biol. 2021 Mar;5:39-57. doi: 10.1146/annurev-cancerbio-043020-125955. Epub 2020 Dec 8. PMID: 34222745; PMCID: PMC8248658.
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