Review ArticleReview

Targeting PP2A for cancer therapeutic modulation

Halle Ronk, Jared S. Rosenblum, Timothy Kung and Zhengping Zhuang
Cancer Biology & Medicine October 2022, 19 (10) 1428-1439; DOI: https://doi.org/10.20892/j.issn.2095-3941.2022.0330

References

  1. 1.↵
    2. Kinch MS.
    An analysis of FDA-approved drugs for oncology. Drug Discov Today. 2014; 19: 1831–5.
    OpenUrl
  2. 2.↵
    2. Schirracher V.
    From chemotherapy to biological therapy: a review of novel concepts to reduce the side effects of systemic cancer treatment. Int J Oncol. 2019; 54: 407–19.
    OpenUrlCrossRef
  3. 3.↵
    2. Sanchez-Vega F,
    3. Mina M,
    4. Armenia J,
    5. Chatila WK,
    6. Luna A,
    7. La KC, et al.
    Oncogenic signaling pathways in the cancer genome atlas. Cell. 2018; 173: 321–337.e10.
    OpenUrlCrossRefPubMed
  4. 4.↵
    2. Hong CS,
    3. Ho W,
    4. Zhang C,
    5. Yang C,
    6. Elder JB,
    7. Zhuang Z.
    LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential. Cancer Biol Ther. 2015; 16: 821–33.
    OpenUrlCrossRefPubMed
  5. 5.↵
    2. Ruediger R,
    3. Van Wart Hood JE,
    4. Walter G.
    Constant expression and activity of protein phosphatase 2A in synchronized cells. Mol Cell Biol. 1991; 11: 4282–5.
    OpenUrlAbstract/FREE Full Text
  6. 6.
    2. Seshacharyulu P,
    3. Pandey P,
    4. Datta K,
    5. Batra SK.
    Phosphatase: PP2A structural importance, regulation, and its aberrant expression in cancer. Cancer Lett. 2013; 335: 9–18.
    OpenUrlCrossRefPubMed
  7. 7.
    2. Reynhout S,
    3. Janssens V.
    Physiologic functions of PP2A: Lessons from genetically modified mice. Biochim Biophys Acta Mol Cell Res. 2019; 1866: 31–50.
    OpenUrlCrossRefPubMed
  8. 8.↵
    2. McCright B,
    3. Virshup DM.
    Identification of a new family of protein phosphatase 2A regulatory subunits. J Biol Chem. 1995; 270: 26123–8.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    2. Janssens V,
    3. Goris J,
    4. Van Hoof C.
    PP2A: the expected tumor suppressor. Curr Opin Genet. 2005; 15: 34–41.
    OpenUrlCrossRefPubMedWeb of Science
  10. 10.↵
    2. Guo F,
    3. Stanevich V,
    4. Wlodarchak N,
    5. Sengupta R,
    6. Jiang L,
    7. Satyshur KA, et al.
    Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone. Cell Res. 2014; 24: 190–203.
    OpenUrlCrossRefPubMedWeb of Science
  11. 11.↵
    2. D’Arcy BM,
    3. Swingle MR,
    4. Papke CM,
    5. Abney KA,
    6. Bouska ES,
    7. Prakash A, et al.
    The antitumor drug LB-100 is a catalytic inhibitor of protein phosphatase 2A (PPP2CA) and 5 (PPP5C) coordinating with the active-site catalytic metals in PPP5C. Mol Cancer Ther. 2019; 18: 555–6.
    OpenUrl
  12. 12.↵
    2. Chen X,
    3. Lu S,
    4. Zhang Y.
    Identification and biochemical characterization of protein phosphatase 5 from the cantharidin-producing blister beetle, Epicauta chinensis. Int J Mol Sci. 2013; 14: 24501–13.
    OpenUrl
  13. 13.↵
    2. Pan M,
    3. Cao J,
    4. Fan Y.
    Insight into norcantharidin, a small-molecule synthetic compound with potential multi-target anticancer activities. Chin Med. 2020; 15: 55.
    OpenUrl
  14. 14.↵
    2. Wang G.
    Medical uses of mylabris in ancient China and recent studies. J Ethnopharmacol. 1989; 26: 147–62.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    2. Tu GG,
    3. Zhan JF,
    4. Lv QL,
    5. Wang JQ,
    6. Kuang BH,
    7. Li SH.
    Synthesis and antiproliferative assay of norcantharidin derivatives in cancer cells. Med Chem. 2014; 10: 376–81.
    OpenUrl
  16. 16.↵
    National Library of Medicine (U.S.). A phase Ib open-label study of LB-100 in combination with carboplatin/etoposide/atezolizumab in untreated extensive-stage small cell lung carcinoma. Identifier NCT04560972. 2021, May. https://clinicaltrials.gov/ct2/show/NCT04560972.
  17. 17.
    National Library of Medicine (U.S.). A phase 1b/2 study evaluating the safety and efficacy of intravenous LB-100 in patients with low or intermediate-1 risk myelodysplastic syndromes (MDS) who had disease progression or are intolerant to prior therapy. Identifier NCT03886662. 2019, April. https://clinicaltrials.gov/ct2/show/NCT03886662.
  18. 18.
    National Library of Medicine (U.S.). Phase II trial of LB100, a protein phosphatase 2A inhibitor, in recurrent glioblastoma. Identifier NCT03027388. 2019, January. https://clinicaltrials.gov/ct2/show/NCT03027388.
  19. 19.↵
    National Library of Medicine (U.S.). Safety, tolerability, and preliminary activity of LB-100, an inhibitor of protein phosphatase 2A, in patients with relapsed solid tumors: an open-label, dose escalation, first-in-human, phase I trial. Identifier NCT1837667. 2013, April-2017, January. https://clinicaltrials.gov/ct2/show/NCT01837667.
  20. 20.↵
    2. Bryant JP,
    3. Levy A,
    4. Heiss J,
    5. Banasavadi-Siddegowda YK.
    Review of PP2A tumor biology and antitumor effects of PP2A inhibitor LB100 in the nervous system. Cancers. 2021; 13: 3087.
    OpenUrl
  21. 21.↵
    2. Cui J,
    3. Wang H,
    4. Medina R,
    5. Zhang Q,
    6. Xu C,
    7. Indig IH, et al.
    Inhibition of PP2A with LB100 enhances efficacy of CAR-T cell therapy against glioblastoma. Cancers. 2020; 12: 139.
    OpenUrl
  22. 22.↵
    2. Maggio D,
    3. Ho WS,
    4. Breese R,
    5. Walbridge S,
    6. Wang H,
    7. Cui D, et al.
    Inhibition of protein phosphatase-2A with LB-100 enhances antitumor immunity against glioblastoma. J Neuro Oncol. 2020; 148: 231–44.
    OpenUrl
  23. 23.↵
    2. Mirzapoiazova T,
    3. Xiao G,
    4. Mambetsariev B,
    5. Nasser MW,
    6. Miaou E,
    7. Singhal SS, et al.
    Protein phosphatase 2A as a therapeutic target in small cell lung cancer. Mol Cancer Ther. 2021; 20: 1820–35.
    OpenUrlAbstract/FREE Full Text
  24. 24.↵
    2. Uddin MH,
    3. Pimentel JM,
    4. Chatterjee M,
    5. Allen JE,
    6. Zhuang Z,
    7. Wu GS.
    Targeting PP2A inhibits the growth of triple-negative breast cancer cells. Cell Cycle. 2020; 19: 592–600.
    OpenUrl
  25. 25.↵
    2. Yen Y,
    3. Chien M,
    4. Wu P,
    5. Ho C,
    6. Huang KC,
    7. Chiang S, et al.
    Protein phosphatase 2A inactivation induces microsatellite instability, neoantigen production, and immune response. Nature. 2021; 12: 7297.
  26. 26.↵
    2. Zhang C,
    3. Hong CS,
    4. Hu X,
    5. Yang C,
    6. Wang H,
    7. Zhu D, et al.
    Inhibition of protein phosphatase 2A with the small molecule LB100 overcomes cell cycle arrest in osteosarcoma after cisplatin treatment. Cell Cycle. 2015; 14: 2100–8.
    OpenUrl
  27. 27.↵
    2. Liu L,
    3. Wang H,
    4. Cui J,
    5. Zhang Q,
    6. Zhang W,
    7. Xu W, et al.
    Inhibition of protein phosphatase 2A sensitizes mucoepidermoid carcinoma to chemotherapy via the PI3K-AKT pathway in response to insulin stimulus. Cell Physiol Biochem. 2018; 50: 317–31.
    OpenUrl
  28. 28.↵
    2. Song Q,
    3. Wang H,
    4. Jiang D,
    5. Xu C,
    6. Cui J,
    7. Zhang Q, et al.
    Pharmacological inhibition of PP2A overcomes nab-paclitaxel resistance by downregulating MCL1 in esophageal squamous cell carcinoma (ESCC). Cancers (Basel). 2021; 13: 4766.
    OpenUrl
  29. 29.↵
    2. Hu C,
    3. Yu M,
    4. Ren Y,
    5. Li K,
    6. Maggio DM,
    7. Mei C, et al.
    PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation. Sci Rep. 2017; 7: 2894.
    OpenUrl
  30. 30.↵
    2. Lai D,
    3. Chen M,
    4. Su J,
    5. Liu X,
    6. Rothe K,
    7. Hu K, et al.
    PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL+ human leukemia. Sci Trans Med. 2018; 10: 8735.
    OpenUrl
  31. 31.↵
    2. Ho WS,
    3. Sizdahkhani S,
    4. Hao S,
    5. Song H,
    6. Seldomridge A,
    7. Tandle A, et al.
    LB-100, a novel protein phosphatase 2A (PP2A) inhibitor, sensitizes malignant meningioma cells to the therapeutic effects of radiation. Cancer Lett. 2018; 415: 217–26.
    OpenUrl
  32. 32.↵
    2. Hao S,
    3. Song H,
    4. Zhang W,
    5. Seldomridge A,
    6. Jung J,
    7. Giles AJ, et al.
    Protein phosphatase 2A inhibition enhances radiation sensitivity and reduces tumor growth in chordoma. Neuro Oncol. 2018; 20: 799–809.
    OpenUrl
  33. 33.↵
    2. Ostrom QT,
    3. Gittleman H,
    4. Xu J,
    5. Kromer C,
    6. Wolinsky Y,
    7. Kruchko C, et al.
    CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009-2013. Neuro Oncol. 2016; 18 (suppl 5): v1–75.
    OpenUrlCrossRefPubMed
  34. 34.↵
    2. Stupp R,
    3. Mason WP,
    4. van der Bent MJ,
    5. Weller M,
    6. Fisher B,
    7. Taphoorn MJB, et al.
    Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352: 987–96.
    OpenUrlCrossRefPubMedWeb of Science
  35. 35.↵
    2. Yu MW,
    3. Quail DF.
    Immunotherapy for glioblastoma: current progress and challenges. Front Immunol. 2021; 12: 676301.
  36. 36.↵
    2. Bagley SJ,
    3. Desai AS,
    4. Linette GP,
    5. June CH,
    6. O’Rourke DM.
    CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges. Neuro Oncol. 2018; 20: 1429–38.
    OpenUrlCrossRefPubMed
  37. 37.↵
    2. Shechter R,
    3. London A,
    4. Schwartz M.
    Orchestrated leukocyte recruitment to immune-privileged sites: absolute barriers versus educational gates. Nat Rev Immunol. 2013; 13: 206–18.
    OpenUrlCrossRefPubMed
  38. 38.
    2. Louveau A,
    3. Smirnov I,
    4. Keyes TJ,
    5. Eccles JD,
    6. Rouhani SJ,
    7. Peske JD, et al.
    Structural and functional features of central nervous system lymphatic vessels. Nature. 2015; 523: 337–41.
    OpenUrlCrossRefPubMed
  39. 39.
    2. Goldmann J,
    3. Kwidzinski E,
    4. Brandt C,
    5. Mahlo J,
    6. Richter D,
    7. Bechmann I.
    T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa. J Leukoc Biol. 2006; 80: 797–801.
    OpenUrlCrossRefPubMedWeb of Science
  40. 40.↵
    2. Karmur BS,
    3. Philteos J,
    4. Abbasian A,
    5. Zacharia BE,
    6. Lipsman N,
    7. Levin V, et al.
    Blood-brain barrier disruption in neuro-oncology: strategies, failures, and challenges to overcome. Front Oncol. 2020; 10: 563840.
  41. 41.↵
    2. Newick K,
    3. Moon E,
    4. Albelda SM.
    Chimeric antigen receptor T-cell therapy for solid tumors. Mol Ther Oncolytics. 2016; 3: 16006.
    OpenUrl
  42. 42.↵
    2. Taffs RE,
    3. Redegeld FA,
    4. Sitkovsky MV.
    Modulation of cytolytic T lymphocyte functions by an inhibitor of serine/threonine phosphatase, okadaic acid. Enhancement of cytolytic T lymphocyte-mediated cytotoxicity. J Immunol. 1991; 147: 722–8.
    OpenUrlAbstract
  43. 43.↵
    2. Sun J,
    3. Zhang D,
    4. Wu S,
    5. Xu M,
    6. Zhou X,
    7. Lu X, et al.
    Resistance to PD-1/PD-L1 blockade cancer immunotherapy: mechanisms, predictive factors, and future perspectives. Biomark Res. 2020; 8: 35.
    OpenUrl
  44. 44.↵
    2. Yang T,
    3. Kong Z,
    4. Ma W.
    PD-1/PD-L1 immune checkpoint inhibitors in glioblastoma: clinical studies, challenges, and potential. Hum Vaccin Imunother. 2021; 17: 546–53.
    OpenUrl
  45. 45.↵
    2. Nduom EK,
    3. Wei J,
    4. Yaghi NK,
    5. Huang N,
    6. Kong L,
    7. Gabrusiewicz K, et al.
    PD-L1 expression and prognostic impact in glioblastoma. Neuro Oncol. 2016; 18: 195–205.
    OpenUrlCrossRefPubMed
  46. 46.↵
    2. Rudin CM,
    3. Brambilla E,
    4. Faivre-Finn C,
    5. Sage J.
    Small-cell lung cancer. Nat Rev Dis Primers. 2021; 7: 3.
    OpenUrl
  47. 47.↵
    2. Perez EA,
    3. Moreno-Aspitia A,
    4. Thompson EA,
    5. Andorfer CA.
    Adjuvant therapy of triple negative breast cancer. Breast Cancer Res Treat. 2010; 120: 285–91.
    OpenUrlCrossRefPubMedWeb of Science
  48. 48.↵
    2. Rahman M,
    3. Davis SR,
    4. Pumphrey JG,
    5. Bao J,
    6. Nau MM,
    7. Meltzer PS, et al.
    TRAIL induces apoptosis in triple-negative breast cancer cells with a mesenchymal phenotype. Breast Cancer Res Treat. 2009; 113: 217–30.
    OpenUrlCrossRefPubMed
  49. 49.↵
    2. Yuan X,
    3. Gajan A,
    4. Chu Q,
    5. Xiong H,
    6. Wu K,
    7. Wu GS.
    Developing TRAIL/TRAIL-death receptor-based cancer therapies. Cancer Metastasis Rev. 2018; 37: 733–48.
    OpenUrlCrossRefPubMed
  50. 50.↵
    2. Xu J,
    3. Xu Z,
    4. Zhou J,
    5. Zhuang Z,
    6. Wang E,
    7. Boerner, et al.
    Regulation of the Src-PP2A interaction in tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. J Biol Chem. 2013; 288: 33263–71.
    OpenUrlAbstract/FREE Full Text
  51. 51.↵
    2. Rawla P,
    3. Sunkara T,
    4. Barsouk A.
    Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019; 14: 89–103.
    OpenUrlCrossRefPubMed
  52. 52.↵
    2. Sinicrope FA,
    3. Mahoney MR,
    4. Smyrk TC,
    5. Thibodeau SN,
    6. Warren RS,
    7. Bertagnolli MM, et al.
    Prognostic impact of deficient DNA mismatch repair in patients with stage III colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy. J Clin Oncol. 2013; 31: 3664–72.
    OpenUrlAbstract/FREE Full Text
  53. 53.↵
    2. Piñol V,
    3. Castells A,
    4. Andreu M,
    5. Castellví-Bel S,
    6. Alenda C,
    7. Llor X, et al.
    Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA. 2005; 293: 1986–94.
    OpenUrlCrossRefPubMedWeb of Science
  54. 54.↵
    2. Poynter JN,
    3. Siegmund KD,
    4. Weisenberger DJ,
    5. Long TI,
    6. Thibodeau SN,
    7. Lindor N, et al.
    Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screening. Cancer Epidemiol Biomarkers Prev. 2008; 17: 3208–15.
    OpenUrlAbstract/FREE Full Text
  55. 55.↵
    2. Wert-Carvajal C,
    3. Sánchez-García R,
    4. Macías JR,
    5. Sanz-Pamplona R,
    6. Pérez AM,
    7. Alemany R, et al.
    Predicting MHC I restricted T cell epitopes in mice with NAP-CNB, a novel online tool. Sci Rep. 2021; 11: 10780.
    OpenUrl
  56. 56.↵
    National Library of Medicine (U.S.). Study of Induction of PD-1 Blockade in Subjects with Locally Advanced Mismatch Repair Deficient Solid Tumors. Identifier NCT04165772. 2019, November. https://clinicaltrials.gov/ct2/show/NCT04165772.
  57. 57.↵
    2. Cercek A,
    3. Lumish M,
    4. Sinopoli J,
    5. Weiss J,
    6. Shia J,
    7. Lamendola-Essel M, et al.
    PD-1 blockade in mismatch repair-deficient, locally-advanced rectal cancer. N Engl J Med. 2022; 386: 2363–76.
    OpenUrlCrossRefPubMed
  58. 58.↵
    2. Misaghi A,
    3. Goldin A,
    4. Awad M,
    5. Kulidjian AA.
    Osteosarcoma: a comprehensive review. SICOT J. 2018; 4: 12.
    OpenUrl
  59. 59.↵
    2. Bruland OS,
    3. Høifødt H,
    4. Saeter G,
    5. Smeland S,
    6. Fodstad O.
    Hematogenous micrometastases in osteosarcoma patients. Clin Cancer Res. 2005; 11: 4666–73.
    OpenUrlAbstract/FREE Full Text
  60. 60.↵
    2. Bai X,
    3. Zhi X,
    4. Zhang Q,
    5. Liang F,
    6. Chen W,
    7. Liang C, et al.
    Inhibition of protein phosphatase 2A sensitizes pancreatic cancer to chemotherapy by increasing drug perfusion via HIF-1α-VEGF mediated angiogenesis. Cancer Lett. 2014; 55: 281–7.
    OpenUrl
  61. 61.↵
    2. Rosenblum JS,
    3. Pant H.
    CDK5 acts as a surveillance system in the nervous system. New Developments on Signal Transduction Research. UK: Nova Science Pub Inc. 2013:1–47.
  62. 62.↵
    2. Chen J,
    3. Kwong DL,
    4. Cao T,
    5. Hu Q,
    6. Zang L,
    7. Ming X, et al.
    Esophageal squamous cell carcinoma (ESCC): advance in genomics and molecular genetics. Dis Esophagus. 2015; 28: 84–9.
    OpenUrl
  63. 63.↵
    2. Hirano H,
    3. Kato K.
    Systemic treatment of advanced esophageal squamous cell carcinoma: chemotherapy, molecular-targeting therapy, and immunotherapy. Jpn J Clin Oncol. 2019; 49: 412–20.
    OpenUrlPubMed
  64. 64.↵
    2. Kamath K,
    3. Wilson L,
    4. Cabral F,
    5. Jordan MA.
    βIII-tubulin induces paclitaxel resistance in association with reduced effects on microtubule dynamic instability. J Biol Chem. 2005; 280: 12902–7.
    OpenUrlAbstract/FREE Full Text
  65. 65.↵
    2. Davis AS,
    3. Viera AJ,
    4. Mead MD.
    Leukemia: an overview for primary care. Am Fam Physician. 2014; 89: 731–8.
    OpenUrlPubMed
  66. 66.↵
    2. Roboz GJ.
    Current treatment of acute myeloid leukemia. Curr Opin Oncol. 2012; 24: 711–9.
    OpenUrlCrossRefPubMed
  67. 67.↵
    2. Zhou H,
    3. Mak PY,
    4. Mu H,
    5. Ma DH,
    6. Zeng Z,
    7. Cortes J, et al.
    Combined inhibition of β-catenin and Bcr–Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo. Leukemia. 2017; 31: 2065–74.
    OpenUrlCrossRef
  68. 68.↵
    2. Jamieson CHM,
    3. Ailles LE,
    4. Dylla SJ,
    5. Muijtjens M,
    6. Jones C,
    7. Zehnder JL, et al.
    Granulocyte-macrophage progenitors in blast-crisis CML. N Engl J Med. 2004; 351: 657–67.
    OpenUrlCrossRefPubMedWeb of Science
  69. 69.↵
    2. Okano A,
    3. Miyawaki S,
    4. Hongo H,
    5. Dofuku S,
    6. Teranishi Y,
    7. Mitsui J, et al.
    Associations of pathological diagnosis and genetic abnormalities in meningiomas with the embryological origins of the meninges. Sci Rep. 2021; 11: 6987.
    OpenUrl
  70. 70.↵
    2. Buerki RA,
    3. Horbinski CM,
    4. Kruser T,
    5. Horowitz PM,
    6. James CD,
    7. Lukas RV.
    An overview of meningiomas. Future Oncol. 2018; 14: 2161–77.
    OpenUrlPubMed
  71. 71.↵
    2. Walcott BP,
    3. Nahed BV,
    4. Mohyeldin A,
    5. Coumans JV,
    6. Kahle KT,
    7. Ferreira MJ.
    Chordoma: current concepts, management, and future directions. Lancet Oncol. 2012; 13: e69–76.
    OpenUrlCrossRefPubMedWeb of Science
  72. 72.↵
    2. Krause DS,
    3. Van Etten RA.
    Tyrosine kinases as targets for cancer therapy. N Engl J Med. 2005; 353: 172–87.
    OpenUrlCrossRefPubMedWeb of Science
  73. 73.↵
    2. Shah DR,
    3. Shah RR,
    4. Morganroth J.
    Tyrosine kinase inhibitors: their on-target toxicities as potential indicators of efficacy. Drug Saf. 2013; 36: 413–26.
    OpenUrlCrossRefPubMed
  74. 74.↵
    2. Valdiglesias V,
    3. Prego-Faraldo MV,
    4. Pásaro E,
    5. Méndez J,
    6. Laffon B.
    Okadaic acid: more than a diarrheic toxin. Mar Drugs. 2013; 11: 4328–49.
    OpenUrlCrossRef
  75. 75.↵
    2. Hoffman A,
    3. Taleski G,
    4. Sontag E.
    The protein serine/threonine phosphatases PP2A, PP1, and calcineurin: a triple threat in the regulation of the neuronal cytoskeleton. Mol and Cel Neurosci. 2017; 84: 119–31.
    OpenUrl
  76. 76.↵
    2. Ajay AK,
    3. Upadhyay AK,
    4. Singh S,
    5. Vijayakumar MV,
    6. Kumari R,
    7. Pandey V, et al.
    Cdk5 phosphorylates non-genotoxically overexpressed p53 following inhibition of PP2A to induce cell cycle arrest/apoptosis and inhibits tumor progression. Mol Cancer. 2010; 9: 204.
    OpenUrlCrossRefPubMed
  77. 77.↵
    2. Chung V,
    3. Mansfield AS,
    4. Braiteh F,
    5. Richards D,
    6. Durivage H,
    7. Ungerleider RS, et al.
    Safety, tolerability, and preliminatry activity of LB-100, an inhibitor of protein phosphatase 2A, in patients with relapsed solid tumors: an open-label, dose escalation, first-in-human, phase I trial. Clin Cancer Res. 2017; 23: 3277–84.
    OpenUrlAbstract/FREE Full Text
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