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Scientific References

Recently published articles supporting Lixte’s clinical development plan.

Safety

  1. Chung V et. al. 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. Clin Cancer Res. 2017;23(13):3277-84.

Immunotherapy combinations

  1. Ho WS et. al. Pharmacologic inhibition of protein phosphatase-2A achieves durable immune-mediated antitumor activity when combined with PD-1 blockade. Nat Commun. 2018;9(1):2126.
  2. Yen YT et. al. Protein phosphatase 2A inactivation induces microsatellite instability, neoantigen production and immune response. Nat Commun. 2021;12(1):7297.
  3. Ho WS et. al. PP2Ac/STRN4 negatively regulates STING-type I IFN signaling in tumor-associated macrophages. The Journal of Clinical Investigation. 2023;133(6).
  4. Maggio D et. al. Inhibition of protein phosphatase-2A with LB-100 enhances antitumor immunity against glioblastoma. J Neurooncol. 2020;148(2):231-44.
  5. Samstein RM et. al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51(2):202-6.
  6. Mirzapoiazova T et al. Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer. Mol Cancer Ther. 2021 Oct;20(10):1820-1835. doi: 10.1158/1535-7163.MCT-21-0013. Epub 2021 Jul 12.PMID: 34253596
  7. Hinchcliff E et al. Loss-of-function mutations in PPP2R1A Correlate with Exceptional Survival in Ovarian Clear Cell Carcinomas Treated with Immune Checkpoint Inhibitors. Gynecologic Oncology Volume 166, Supplement 1, August 2022, Page S66. doi: 10.1016/S0090-8258(22)01325-7

Chemotherapy combinations

  1. Song Q et. al. Pharmacological Inhibition of PP2A Overcomes Nab-Paclitaxel Resistance by Downregulating MCL1 in Esophageal Squamous Cell Carcinoma (ESCC). Cancers (Basel). 2021;13(19).
  2. Chang KE et. al. The protein phosphatase 2A inhibitor LB100 sensitizes ovarian carcinoma cells to cisplatin-mediated cytotoxicity. Mol Cancer Ther. 2015;14(1):90-100.
  3. Hong CS et. al. LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential. Cancer Biol Ther. 2015;16(6):821-33.

Future clinical development

  1. Dias MH et. al. Paradoxical activation of oncogenic signaling as a cancer treatment strategy. bioRxiv. 2023:2023.02.06.527335.