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    The UCI Anti-Cancer Challenge posted a video of David Fruman discussing the statin/venetoclax project that was supported by an ACC pilot award.

    https://www.linkedin.com/feed/update/urn:li:activity:7061755978253271040/

    We published a Perspective in Frontiers in Oncology on new therapeutic combinations in high-risk B-ALL

    Buono, R, Alhaddad, M, Fruman, DA. Novel pharmacological and dietary approaches to target mTOR in B-cell acute lymphoblastic leukemia. 2023; 14 April. Oncol., 13: 1162694. doi: 10.3389/fonc.2023.1162694

    We reported that chemical or genetic inhibition of the eIF4F translation initiation complex sensitizes acute lymphoblastic leukemia cells to tyrosine kinase inhibitors.

    Vo, TT, Herzog, L, Buono, R, Lee, JS, Mallya, S, Duong, MR, Thao, J, Gotesman, M, Fruman, DA. Targeting eIF4F translation complex sensitizes B-ALL cells to tyrosine kinase inhibition. 2021. Scientific Reports,11: 21689. doi.org/10.1038/s41598-021-00950-y

    In collaboration with Revolution Medicines, we showed that a novel bi-steric inhibitor of mTORC1 has potent anti-leukemia activity in models of Ph+ B-ALL. The compound, known as RMC-4627, selectively inhibits mTORC1 kinase activity and reactivates the intrinsic tumor suppressor function of 4E-BP1.

    Lee, BJ, Mallya, S, Dinglasan, N, Fung, A, Nguyen, T, Herzog, L, Thao, J, Lorenzana, EG, Wildes, D, Singh, M, Smith, JA, Fruman, DA. Efficacy of novel bi-steric mTORC1 inhibitor in models of B-cell acute lymphoblastic leukemia. 2021. Frontiers in Oncology, Epub Aug 2. doi.org/10.3389/fonc.2021.673213

    We reported a selective “addiction” to the translation initiation factor eIF4E in B-cell leukemia compared to normal B cells.

    Chiu, H, Buono, R, Jackson, LV, Herzog, L, Mallya, S, Conn, C, Ruggero, D, Fruman, DA. Reduced eIF4E function impairs B-cell leukemia without altering normal B-lymphocyte function. 2021. iScience, ePub June 16

    We published a review article in Trends in Cancer on statins and the mevalonate pathway in cancer.

    Juarez D, Fruman, DA. Targeting the mevalonate pathway in cancer. 2021. Trends in Cancer, 7: 525-540.

    We showed that the eIF4G-binding compound SBI-756 disrupts eIF4F formation in lymphoma cells and sensitizes to apoptosis by the BCL2 inhibitor venetoclax.

    Herzog, L, Walters, B, Lee, JS, Chiu, H, Mallya, S, Fung, A, Nguyen, N, Li, B, Pinkerton, AB, Jackson, MR, Schneider, RJ, Ronai, ZA, Fruman, DA. Targeting eIF4F Translation Initiation Complex with SBI-756 Sensitizes B Lymphoma Cells to Venetoclax. 2020. Br. J. Cancer, Epub Dec. 14

    We reported a novel role for the mTORC1/eIF4F axis in antibody class switching.

    Chiu, H, Jackson, LV, Oh, KI, Mai, A, Ronai, ZA, Ruggero, D, Fruman, DA. The mTORC1/4E-BP/eIF4E Axis Promotes Antibody Class Switching in B Lymphocytes. 2019. J. Immunol., 202: 579-590.

    We identified a novel drug combination (statin plus venetoclax) that is effective in various blood cancers. This was published in Science Translational Medicine in June 2018. The UCI School of Biological Sciences press release is here.

    Lee, JS, Roberts, A, Vo, TT, Juarez, D, Bhatt, S, Bellin, RJ, Agarwal, SK, Salem, AH, Xu, T, Jia, J, Li, L, Hanna, JR, Davids, MS, Fleischman, AG, O’Brien, S, Lam, LT, Leverson, JD, Letai, A, Schatz, J, Fruman, DA. Statins enhance efficacy of venetoclax in blood cancers. 2018. Sci. Transl. Med., Jun 13;10(445).

    David Fruman was elected as a AAAS Fellow in 2016. The UCI press release is here.

    Our study of rapamycin mechanism in lymphocytes was published in Science Signaling in May 2016:

    So, L, Lee, J, Palafox, M, Mallya, S, Woxland, C, Arguello, M, Truitt, M, Sonenberg, N, Ruggero, D, Fruman, DA. The 4E-BP/eIF4E axis promotes rapamycin-sensitive growth and proliferation in lymphocytes. 2016. Science Signaling, 9: ra57.

    Check out additional recent reviews and research papers in Cell, Molecular Cancer Therapeutics, Frontiers in Immunology, Journal of Immunology, New England Journal of Medicine, Nature Reviews Drug Discovery, Cancer Discovery, PNAS, and Oncotarget:

    Fruman, DA, Chiu, H, Hopkins, BD, Bagrodia, S, Cantley, LC, Abraham, RT. The PI3K pathway in human disease. 2017. Cell, 170: 605-635. Vo, TT, Lee, JS, Nguyen, D, Lui, B, Pandori, W, Khaw, A, Mallya, S, Lu, M, Müschen, M, Konopleva, M, Fruman, DA. mTORC1 inhibition induces resistance to methotrexate and 6-mercaptopurine in Ph+ and Ph-like B-ALL. 2017. Mol. Cancer Therap., Epub May 31. Chiu, H, Mallya, S, Nguyen, P, Mai, A, Winkler, DG, McGovern, K, Kutok, JL, Fruman, DA. The selective PI3K p110d inhibitor IPI-3063 potently suppresses B cell survival, proliferation and differentiation. 2017. Front. Immunol., 8: 747. Pai, C, Walsh, CM, Fruman, DA. Context-specific function of S6K2 in helper T cell differentiation. 2016. J. Immunol., 197: 3049-58. Lee, JS, Vo, TT, Fruman, DA. Targeting mTOR for the treatment of B cell malignancies. Br. J. Clin. Pharmacol., Epub Jan. 25. Vo, TT, Fruman, DA. INPP4B is a tumor suppressor in the context of PTEN deficiency. 2015. Cancer Discov. 5: 697-700. Lee, JS, Tang, SS, Ortiz, V, Vo, TT, Fruman, DA. MCL-1-independent mechanisms of synergy between dual PI3K/mTOR and BCL-2 inhibition in diffuse large B cell lymphoma. 2015. Oncotarget, 6: 35202-17. Fruman, DA, Cantley, LC. Idelalisib: a PI3K delta inhibitor for B cell malignancies. 2014. New Engl. J. Med., 370: 1061-2. Fruman, DA, Rommel, C. PI3K and cancer: lessons, challenges, and opportunities. 2014. Nat. Rev. Drug Discov., 13:140-56. Beagle, BR, Nguyen, D, Mallya, S, Tang, SS, Lu, M, Zeng, A, Konopleva, M, Vo, TT, Fruman, DA. mTOR inhibitors synergize with histone deacetylase inhibitors to kill B-cell acute lymphoblastic leukemia cells. 2015. Oncotarget, 6: 2088-100. Limon, JJ, So, L, Jellbauer, S, Chiu, H, Corado, J, Sykes, S, Raffatellu, M, Fruman, DA. mTOR kinase inhibitors promote antibody class switching via mTORC2 inhibition. 2014. PNAS, 111:E5076-85.

    David Fruman obtained a NIH-BEST award for professional development of UCI graduate students and postdocs:

    http://sites.bio.uci.edu/2014/10/uci-receives-nih-grant-improve-options-doctoral-graduates-across-science-related-careers/

    Trang Vo, postdoctoral fellow, was awarded a NIH F32 fellowship starting in July 2014.

    David Fruman is quoted in a HealthDay news article about the PI3K delta inhibitor results reported in New England Journal:

    http://health.usnews.com/health-news/articles/2014/03/12/experimental-drug-may-boost-leukemia-survival-without-chemo