CRISPRi screening identifies PIKfyve as a co-therapeutic target for obinutuzumab

References

[1] Palmer AC, Sorger PK. combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy. Cell. 2017; 171(7): 1678-1691. e1613.

[2] Alduaij W, Ivanov A, Honeychurch J, et al. Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies. Blood. 2011; 117(17): 4519-4529.

[3] Herter S, Herting F, Muth G, et al. GA101 P329GLALA, a variant of obinutuzumab with abolished ADCC, ADCP and CDC function but retained cell death induction, is as efficient as rituximab in B-cell depletion and antitumor activity. Haematologica. 2018; 103(2): e78-e81.

[4] Horlbeck MA, Gilbert LA, Villalta JE, et al. Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. eLife. 2016; 5: e19760.

[5] Krishna S, Palm W, Lee Y, et al. PIKfyve regulates vacuole maturation and nutrient recovery following engulfment. Dev Cell. 2016; 38(5): 536-547.

[6] Radulovic M, Schink KO, Wenzel EM, et al. ESCRT-mediated lysosome repair precedes lysophagy and promotes cell survival. Embo j. 2018; 37(21).

[7] Bhagwat SV, Gokhale PC, Crew AP, et al. Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin. Molec Cancer Therapeut. 2011; 10(8): 1394-1406.

[8] Gayle S, Landrette S, Beeharry N, et al. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017; 129(13): 1768-1778.

[9] Ono Y, Matsuzawa K, Ikenouchi J. mTORC2 suppresses cell death induced by hypo-osmotic stress by promoting sphingomyelin transport. J Cell Biol. 2022; 221(4).

[10] Choy CH, Saffi G, Gray MA, et al. Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence. J Cell Sci. 2018; 131(10).

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