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Andriy  Marusyk

Andriy Marusyk, PhD

Program: Tumor Microenvironment and Metastasis

Research Program: Cancer Biology & Evolution Program

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  • Overview

    The main focus of research in my lab is filling this gap through development of experimental models that allow characterization and quantification of dynamics of populations of cancers cells under base-like conditions as well as under the stress of anti-cancer therapies.  Another major research effort is centered on characterization of interactions between malignant cells and tumor associated fibroblasts with the aim of developing means to overcome stromal resistance to anti-cancer therapies.


    • Tumor Microenvironment and Metastasis
    • Breast Oncology
    • Cancer Biology & Evolution Program
    • Center of Excellence for Evolutionary Therapy
    • Lung Cancer Center of Excellence

    Education & Training


    • Taras Shevchenko National University, MS - Biology, Cell Biology and Genetic Engineering
    • University of Colorado, PhD - Biophysics and Molecular Genetics


    • University of Colorado Health Sciences Center -
    • - Dana Farber Cancer Institute & Harvard Medical School
  • Research Interest

    Tumors are mini eco-systems, where evolving populations of genetically and phenotypically heterogeneous malignant cells are engaged in a network of reciprocal interactions with multiple normal cell types as well as with non-cellular components of tumor micro and macro environment. Research over recent decades shed light on molecular pathways essential for cancer cell survival, leading to development of multiple novel therapeutic approaches. Unfortunately, almost in all cases anti-cancers therapies provide only a temporary success, as tumors eventually relapse owing to outgrowth of therapy-resistant phenotypes. Preventing and limiting this outgrowth cannot be achieved only by focusing on proximal molecular mechanisms of resistance. We also need to develop adequate level of understanding of evolutionary dynamics, a knowledge that is mostly lacking.

  • Publications

    • Janiszewska M, Tabassum DP, Castaño Z, Cristea S, Yamamoto KN, Kingston NL, Murphy KC, Shu S, Harper NW, Del Alcazar CG, Alečković M, Ekram MB, Cohen O, Kwak M, Qin Y, Laszewski T, Luoma A, Marusyk A, Wucherpfennig KW, Wagle N, Fan R, Michor F, McAllister SS, Polyak K. Author Correction: Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments. Nat Cell Biol. 2024 May.26(5):841. Pubmedid: 38443568.
    • Miroshnychenko D, Miti T, Kumar P, Miller A, Laurie M, Giraldo N, Bui MM, Altrock PM, Basanta D, Marusyk A. Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles. Cancer Res. 2023 Nov.83(22):3681-3692. Pubmedid: 37791818. Pmcid: PMC10646478.
    • Capp JP, Thomas F, Marusyk A, M Dujon A, Tissot S, Gatenby R, Roche B, Ujvari B, DeGregori J, Brown JS, Nedelcu AM. The paradox of cooperation among selfish cancer cells. Evol Appl. 2023 Jul.16(7):1239-1256. Pubmedid: 37492150. Pmcid: PMC10363833.
    • Gatenbee CD, Baker AM, Prabhakaran S, Swinyard O, Slebos RJC, Mandal G, Mulholland E, Andor N, Marusyk A, Leedham S, Conejo-Garcia JR, Chung CH, Robertson-Tessi M, Graham TA, Anderson ARA. Virtual alignment of pathology image series for multi-gigapixel whole slide images. Nat Commun. 2023 Jul.14(1):4502. Pubmedid: 37495577. Pmcid: PMC10372014.
    • Miroshnychenko D, Miti T, Miller A, Kumar P, Laurie M, Bui MM, Altrock PM, Basanta D, Marusyk A. Paracrine enhancement of tumor cell proliferation provides indirect stroma-mediated chemoresistance via acceleration of tumor recovery between chemotherapy cycles. bioRxiv. 2023 Feb. Pubmedid: 36798328. Pmcid: PMC9934626.
    • Adhikari E, Liu Q, Johnson J, Stewart P, Marusyk V, Fang B, Izumi V, Bowers K, Guzman KM, Koomen JM, Marusyk A, Lau EK. Brain metastasis-associated fibroblasts secrete fucosylated PVR/CD155 that induces breast cancer invasion. Cell Rep. 2023 Dec.42(12):113463. Pubmedid: 37995180.
    • Vander Velde R, Shaffer S, Marusyk A. Integrating mutational and nonmutational mechanisms of acquired therapy resistance within the Darwinian paradigm. Trends Cancer. 2022 Jun.8(6):456-466. Pubmedid: 35307314.
    • Somarelli JA, DeGregori J, Gerlinger M, Heng HH, Marusyk A, Welch DR, Laukien FH. Questions to guide cancer evolution as a framework for furthering progress in cancer research and sustainable patient outcomes. Med Oncol. 2022 Jul.39(9):137. Pubmedid: 35781581. Pmcid: PMC9252949.
    • Farrokhian N, Maltas J, Dinh M, Durmaz A, Ellsworth P, Hitomi M, McClure E, Marusyk A, Kaznatcheev A, Scott JG. Measuring competitive exclusion in non-small cell lung cancer. Sci Adv. 2022 Jul.8(26):eabm7212. Pubmedid: 35776787.
    • Remsing Rix LL, Sumi NJ, Hu Q, Desai B, Bryant AT, Li X, Welsh EA, Fang B, Kinose F, Kuenzi BM, Chen YA, Antonia SJ, Lovly CM, Koomen JM, Haura EB, Marusyk A, Rix U. IGF-binding proteins secreted by cancer-associated fibroblasts induce context-dependent drug sensitization of lung cancer cells. Sci Signal. 2022 Aug.15(747):eabj5879. Pubmedid: 35973030. Pmcid: PMC9528501.
    • Foo J, Basanta D, Rockne RC, Strelez C, Shah C, Ghaffarian K, Mumenthaler SM, Mitchell K, Lathia JD, Frankhouser D, Branciamore S, Kuo YH, Marcucci G, Vander Velde R, Marusyk A, Hang S, Hari K, Jolly MK, Hatzikirou H, Poels K, Spilker M, Shtylla B, Robertson-Tessi M, Anderson ARA. Roadmap on plasticity and epigenetics in cancer. Phys Biol. 2022 Apr.19(3). Pubmedid: 35078159. Pmcid: PMC9190291.
    • Miroshnychenko D, Baratchart E, Ferrall-Fairbanks MC, Velde RV, Laurie MA, Bui MM, Tan AC, Altrock PM, Basanta D, Marusyk A. Spontaneous cell fusions as a mechanism of parasexual recombination in tumour cell populations. Nat Ecol Evol. 2021 Mar.5(3):379-391. Pubmedid: 33462489.
    • Capp JP, DeGregori J, Nedelcu AM, Dujon AM, Boutry J, Pujol P, Alix-Panabières C, Hamede R, Roche B, Ujvari B, Marusyk A, Gatenby R, Thomas F. Group phenotypic composition in cancer. Elife. 2021 Mar.10. Pubmedid: 33784238. Pmcid: PMC8009660.
    • Edwards J, Marusyk A, Basanta D. Selection-driven tumor evolution with public goods leads to patterns of clonal expansion consistent with neutral growth. iScience. 2021 Jan.24(1):101901. Pubmedid: 33364589. Pmcid: PMC7753957.
    • Dujon AM, Aktipis A, Alix-Panabières C, Amend SR, Boddy AM, Brown JS, Capp JP, DeGregori J, Ewald P, Gatenby R, Gerlinger M, Giraudeau M, Hamede RK, Hansen E, Kareva I, Maley CC, Marusyk A, McGranahan N, Metzger MJ, Nedelcu AM, Noble R, Nunney L, Pienta KJ, Polyak K, Pujol P, Read AF, Roche B, Sebens S, Solary E, Staňková K, Swain Ewald H, Thomas F, Ujvari B. Identifying key questions in the ecology and evolution of cancer. Evol Appl. 2021 Apr.14(4):877-892. Pubmedid: 33897809. Pmcid: PMC8061275.
    • Vander Velde R, Yoon N, Marusyk V, Durmaz A, Dhawan A, Miroshnychenko D, Lozano-Peral D, Desai B, Balynska O, Poleszhuk J, Kenian L, Teng M, Abazeed M, Mian O, Tan AC, Haura E, Scott J, Marusyk A. Resistance to targeted therapies as a multifactorial, gradual adaptation to inhibitor specific selective pressures. Nat Commun. 2020 May.11(1):2393. Pubmedid: 32409712. Pmcid: PMC7224215.
    • Enderling H, Altrock PM, Andor N, Basanta D, Brown JS, Gatenby RA, Marusyk A, Rejniak KA, Silva A, Anderson ARA. High School Internship Program in Integrated Mathematical Oncology (HIP IMO): Five-Year Experience at Moffitt Cancer Center. Bull Math Biol. 2020 Jul.82(7):91. Pubmedid: 32648152.
    • Damaghi M, Mori H, Byrne S, Xu L, Chen T, Johnson J, Gallant ND, Marusyk A, Borowsky AD, Gillies RJ. Collagen production and niche engineering: A novel strategy for cancer cells to survive acidosis in DCIS and evolve. Evol Appl. 2020 Dec.13(10):2689-2703. Pubmedid: 33294017. Pmcid: PMC7691473.
    • Marusyk A, Janiszewska M, Polyak K. Intratumor Heterogeneity: The Rosetta Stone of Therapy Resistance. Cancer Cell. 2020 Apr.37(4):471-484. Pubmedid: 32289271. Pmcid: PMC7181408.
    • Taylor-King JP, Baratchart E, Dhawan A, Coker EA, Rye IH, Russnes H, Chapman SJ, Basanta D, Marusyk A. Simulated ablation for detection of cells impacting paracrine signalling in histology analysis. Math Med Biol. 2019 Mar.36(1):93-112. Pubmedid: 29452382. Pmcid: PMC7197102.
    • Kaznatcheev A, Peacock J, Basanta D, Marusyk A, Scott JG. Fibroblasts and alectinib switch the evolutionary games played by non-small cell lung cancer. Nat Ecol Evol. 2019 Mar.3(3):450-456. Pubmedid: 30778184. Pmcid: PMC6467526.
    • Rockne RC, Hawkins-Daarud A, Swanson KR, Sluka JP, Glazier JA, Macklin P, Hormuth D, Jarrett AM, Lima EABDF, Oden J, Biros G, Yankeelov TE, Curtius K, Bakir IA, Wodarz D, Komarova N, Aparicio L, Bordyuh M, Rabadan R, Finley S, Enderling H, Caudell JJ, Moros EG, Anderson ARA, Gatenby R, Kaznatcheev A, Jeavons P, Krishnan N, Pelesko J, Wadhwa RR, Yoon N, Nichol D, Marusyk A, Hinczewski M, Scott JG. The 2019 mathematical oncology roadmap. Phys Biol. 2019 Jun.16(4):041005. Pubmedid: 30991381. Pmcid: PMC6655440.
    • Janiszewska M, Tabassum DP, Castaño Z, Cristea S, Yamamoto KN, Kingston NL, Murphy KC, Shu S, Harper NW, Del Alcazar CG, Alečković M, Ekram MB, Cohen O, Kwak M, Qin Y, Laszewski T, Luoma A, Marusyk A, Wucherpfennig KW, Wagle N, Fan R, Michor F, McAllister SS, Polyak K. Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments. Nat Cell Biol. 2019 Jul.21(7):879-888. Pubmedid: 31263265. Pmcid: PMC6609451.
    • Peluffo G, Subedee A, Harper NW, Kingston N, Jovanović B, Flores F, Stevens LE, Beca F, Trinh A, Reddy Chilamakuri CS, Papachristou EK, Murphy K, Su Y, Marusyk A, D'Santos CS, Rueda OM, Beck AH, Caldas C, Carroll JS, Polyak K. EN1 Is a Transcriptional Dependency in Triple-Negative Breast Cancer Associated with Brain Metastasis. Cancer Res. 2019 Aug.79(16):4173-4183. Pubmedid: 31239270. Pmcid: PMC6698222.
    • Yoon N, Vander Velde R, Marusyk A, Scott JG. Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs. Bull Math Biol. 2018 Jul.80(7):1776-1809. Pubmedid: 29736596.
    • Tavera-Mendoza LE, Westerling T, Libby E, Marusyk A, Cato L, Cassani R, Cameron LA, Ficarro SB, Marto JA, Klawitter J, Brown M. Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells. Proc Natl Acad Sci U S A. 2017 Mar.114(11):E2186-E2194. Pubmedid: 28242709. Pmcid: PMC5358377.
    • Dhawan A, Nichol D, Kinose F, Abazeed ME, Marusyk A, Haura EB, Scott JG. Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer. Sci Rep. 2017 Apr.7(1):1232. Pubmedid: 28450729. Pmcid: PMC5430816.
    • Scott J, Marusyk A. Somatic clonal evolution: A selection-centric perspective. BBA. Reviews on cancer. 2017 Apr.1867(2):139-150. Pubmedid: 28161395.
    • Marusyk A, Tabassum D, Janiszewska M, Place A, Trinh A, Rozhok AI, Pyne S, Guerriero J, Shu S, Ekram M, Ishkin A, Cahill DP, Nikolsky Y, Chan TA, Rimawi MF, Hilsenbeck SG, Schiff R, Osborne CK, Letai A, Polyak K. Spatial Proximity to Fibroblasts Impacts Molecular Features and Therapeutic Sensitivity of Breast Cancer Cells Influencing Clinical Outcomes. Cancer Res. 2016 Nov.76(22):6495-6506. Pubmedid: 27671678. Pmcid: PMC5344673.
    • Su Y, Subedee A, Bloushtain-Qimron N, Savova V, Krzystanek M, Li L, Marusyk A, Tabassum DP, Zak A, Flacker MJ, Li M, Lin JJ, Sukumar S, Suzuki H, Long H, Szallasi Z, Gimelbrant A, Maruyama R, Polyak K. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer. Cell Rep. 2015 Jun.11(10):1549-1563. Pubmedid: 26051943.
    • Marusyk A, Tabassum DP, Altrock PM, Almendro V, Michor F, Polyak K. Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity. Nature. 2014 Oct.514(7520):54-58. Pubmedid: 25079331. Pmcid: PMC4184961.
    • Chin YR, Yoshida T, Marusyk A, Beck AH, Polyak K, Toker A. Targeting Akt3 signaling in triple-negative breast cancer. Cancer Res. 2014 Feb.74(3):964-973. Pubmedid: 24335962. Pmcid: PMC3946502.
    • Almendro V, Cheng YK, Randles A, Itzkovitz S, Marusyk A, Ametller E, Gonzalez-Farre X, Muñoz M, Russnes HG, Helland A, Rye IH, Borresen-Dale AL, Maruyama R, van Oudenaarden A, Dowsett M, Jones RL, Reis-Filho J, Gascon P, Gönen M, Michor F, Polyak K. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep. 2014 Feb.6(3):514-527. Pubmedid: 24462293. Pmcid: PMC3928845.
    • Cuiffo BG, Campagne A, Bell GW, Lembo A, Orso F, Lien EC, Bhasin MK, Raimo M, Hanson SE, Marusyk A, El-Ashry D, Hematti P, Polyak K, Mechta-Grigoriou F, Mariani O, Volinia S, Vincent-Salomon A, Taverna D, Karnoub AE. MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis. Cell Stem Cell. 2014 Dec.15(6):762-774. Pubmedid: 25515522.
    • Polyak K, Marusyk A. Cancer: Clonal cooperation. Nature. 2014 Apr.508(7494):52-53. Pubmedid: 24695309.
    • Almendro V, Marusyk A, Polyak K. Cellular heterogeneity and molecular evolution in cancer. Annu Rev Pathol. 2013 Jan.8:277-302. Pubmedid: 23092187.
    • Marusyk A, Almendro V, Polyak K. Intra-tumour heterogeneity: a looking glass for cancer?. Nat Rev Cancer. 2012 Apr.12(5):323-334. Pubmedid: 22513401.
    • Henry CJ, Marusyk A, DeGregori J. Aging-associated changes in hematopoiesis and leukemogenesis: what's the connection?. Aging (Albany NY). 2011 Jun.3(6):643-656. Pubmedid: 21765201. Pmcid: PMC3164372.
    • Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, Bloushtain-Qimron N, Kim JJ, Choudhury SA, Maruyama R, Wu Z, Gönen M, Mulvey LA, Bessarabova MO, Huh SJ, Silver SJ, Kim SY, Park SY, Lee HE, Anderson KS, Richardson AL, Nikolskaya T, Nikolsky Y, Liu XS, Root DE, Hahn WC, Frank DA, Polyak K. The JAK2/STAT3 signaling pathway is required for growth of CD44⁺CD24⁻ stem cell-like breast cancer cells in human tumors. J Clin Invest. 2011 Jul.121(7):2723-2735. Pubmedid: 21633165. Pmcid: PMC3223826.
    • Lyons TR, O'Brien J, Borges VF, Conklin MW, Keely PJ, Eliceiri KW, Marusyk A, Tan AC, Schedin P. Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2. Nat Med. 2011 Aug.17(9):1109-1115. Pubmedid: 21822285. Pmcid: PMC3888478.
    • Marusyk A, Porter CC, Zaberezhnyy V, DeGregori J. Irradiation selects for p53-deficient hematopoietic progenitors. PLoS Biol. 2010 Mar.8(3):e1000324. Pubmedid: 20208998. Pmcid: PMC2830447.
    • Henry CJ, Marusyk A, Zaberezhnyy V, Adane B, DeGregori J. Declining lymphoid progenitor fitness promotes aging-associated leukemogenesis. Proc Natl Acad Sci U S A. 2010 Dec.107(50):21713-21718. Pubmedid: 21098275. Pmcid: PMC3003039.
    • Fleenor CJ, Marusyk A, DeGregori J. Ionizing radiation and hematopoietic malignancies: altering the adaptive landscape. Cell Cycle. 2010 Aug.9(15):3005-3011. Pubmedid: 20676038. Pmcid: PMC3040925.
    • Marusyk A, Casás-Selves M, Henry CJ, Zaberezhnyy V, Klawitter J, Christians U, DeGregori J. Irradiation alters selection for oncogenic mutations in hematopoietic progenitors. Cancer Res. 2009 Sep.69(18):7262-7269. Pubmedid: 19738065. Pmcid: PMC2745506.
    • Marusyk A, DeGregori J. Declining cellular fitness with age promotes cancer initiation by selecting for adaptive oncogenic mutations. Biochim Biophys Acta. 2008 Jan.1785(1):1-11. Pubmedid: 17980163. Pmcid: PMC2234267.
    • Marusyk A, DeGregori J. Replicational stress selects for p53 mutation. Cell Cycle. 2007 Sep.6(17):2148-2151. Pubmedid: 17786047. Pmcid: PMC2394679.
    • Marusyk A, Wheeler LJ, Mathews CK, DeGregori J. p53 mediates senescence-like arrest induced by chronic replicational stress. Mol Cell Biol. 2007 Aug.27(15):5336-5351. Pubmedid: 17515610. Pmcid: PMC1952086.
    • Marusyk A, DeGregori J. Building a better model of cancer. Cell Div. 2006 Oct.1:24. Pubmedid: 17049090. Pmcid: PMC1622745.
    • Bilousova G, Marusyk A, Porter CC, Cardiff RD, DeGregori J. Impaired DNA replication within progenitor cell pools promotes leukemogenesis. PLoS Biol. 2005 Dec.3(12):e401. Pubmedid: 16277552. Pmcid: PMC1283331.
    • Jiang X, Huang F, Marusyk A, Sorkin A. Grb2 regulates internalization of EGF receptors through clathrin-coated pits. Mol Biol Cell. 2003 Mar.14(3):858-870. Pubmedid: 12631709. Pmcid: PMC151565.
  • Grants

    • Title: STEER: Strategy for Therapeutic Extinction of Evolving Resistance in lung cancer
      Sponsor: Moffitt Cancer Center
      PI (Contact): Robertson-Tessi, M., CO-PI: Marusyk, A.
    • Title: The Delta Ecology of NSCLC Treatment
      Sponsor: Nat Institutes of Health
      PI (Contact): Anderson, A., PI (MPI): Gatenby, R., Project PI: Marusyk, A., Core PI/Director: Brown, J.
    • Title: Extending experimental evolutionary game theory in cancer in vivo to enable clinical translation: integrating spatio-temporal dynamics using mathematical modeling
      Sponsor: Nat Institutes of Health
      PI: Marusyk, A.
    • Title: Feasibility of Generating Novel Translational and Therapeutic Strategies based on a Multicenter, Pediatric and AYA Evolutionary Tumor Board; pedsETB
      Sponsor: Florida Biomedical Research Program (FBRP)
      PI: Metts, J., CO-PI: Robertson-Tessi, M., CO-PI: Anderson, A., CO-PI: Brown, J., CO-PI: Marusyk, A.
    • Title: Exploiting Ecology and Evolution to Prevent Therapy Resistance in EGFR-Driven Lung Cancer
      Sponsor: Nat Institutes of Health
      PI: Marusyk, A.

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