Effect of excessive activation of PI3K signaling pathway on the prognosis of patients with non-Hodgkin lymphoma and the efficacy of targeted drugs

doi:10.3760/cma.j.cn371439-20200615-00024

Abstract

Abstract:

The over-activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamcyin (mTOR) pathway is closely related to the occurrence, development and clinical prognosis of malignant tumors. Taking this signal pathway as a target can effectively inhibit tumor progression. At present, the Food and Drug Administration of the United States has approved three drugs (CAL-101, BAY80-6946, IPI-145) for the treatment of recurrent and refractory indolent non-Hodgkin lymphoma, which demonstrates significant efficacy and a manageable safety profile.

Key words: Lymphoma, Phosphatidylinositols, Molecular targeted therapy

Qiao Wei, Song Teng, Chen Xinrui, Wang Huaqing. Effect of excessive activation of PI3K signaling pathway on the prognosis of patients with non-Hodgkin lymphoma and the efficacy of targeted drugs[J]. Journal of International Oncology, 2021, 48(2): 121-124.

References 27

[1]	Jain T, Sauter CS, Shah GL, et al. Safety and feasibility of chimeric antigen receptor T cell therapy after allogeneic hematopoietic cell transplantation in relapsed/refractory B cell non-Hodgkin lymphoma[J]. Leukemia, 2019,33(10):2540-2544. DOI: 10.1038/s41375-019-0476-y. doi: 10.1038/s41375-019-0476-y pmid: 31114023
[2]	Yuan T, Yang Y, Chen J, et al. Regulation of PI3K signaling in T-cell acute lymphoblastic leukemia: a novel PTEN/Ikaros/miR-26b mechanism reveals a critical targetable role for PIK3CD[J]. Leukemia, 2017,31(11):2355-2364. DOI: 10.1038/leu.2017.80. doi: 10.1038/leu.2017.80 pmid: 28280276
[3]	Yang J, Nie J, Ma X, et al. Targeting PI3K in cancer: mechanisms and advances in clinical trials[J]. Mol Cancer, 2019,18(1):26. DOI: 10.1186/s12943-019-0954-x. doi: 10.1186/s12943-019-0954-x pmid: 30782187
[4]	Sapon-Cousineau V, Sapon-Cousineau S, Assouline S. PI3K inhibitors and their role as novel agents for targeted therapy in lymphoma[J]. Curr Treat Options Oncol, 2020,21(6):51. DOI: 10.1007/s11864-020-00746-8. doi: 10.1007/s11864-020-00746-8 pmid: 32356174
[5]	Manning BD, Toker A. AKT/PKB signaling: navigating the network[J]. Cell, 2017,169(3):381-405. DOI: 10.1016/j.cell.2017.04.001. doi: 10.1016/j.cell.2017.04.001 pmid: 28431241
[6]	Luongo F, Colonna F, Calapà F, et al. PTEN tumor-suppressor: the dam of stemness in cancer[J]. Cancers (Basel), 2019,11(8):1076. DOI: 10.3390/cancers11081076. doi: 10.3390/cancers11081076
[7]	Papa A, Wan L, Bonora M, et al. Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function[J]. Cell, 2014,157(3):595-610. DOI: 10.1016/j.cell.2014.03.027. doi: 10.1016/j.cell.2014.03.027
[8]	Li C, Xu Y, Xin P, et al. Role and mechanism of PTEN in Burkitt's lymphoma[J]. Oncol Rep, 2020,43(2):481-490. DOI: 10.3892/or.2020.7457. doi: 10.3892/or.2020.7457 pmid: 31922234
[9]	Wang X, Cao X, Sun R, et al. Clinical significance of PTEN deletion, mutation, and loss of PTEN expression in de novo diffuse large B-cell lymphoma[J]. Neoplasia, 2018,20(6):574-593. DOI: 10.1016/j.neo.2018.03.002. doi: 10.1016/j.neo.2018.03.002 pmid: 29734016
[10]	Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation[J]. Nat Rev Immunol, 2003,3(4):317-330. DOI: 10.1038/nri1056. doi: 10.1038/nri1056 pmid: 12669022
[11]	Cui W, Cai Y, Wang W, et al. Frequent copy number variations of PI3K/AKT pathway and aberrant protein expressions of PI3K subunits are associated with inferior survival in diffuse large B cell lymphoma[J]. J Transl Med, 2014,12:10. DOI: 10.1186/1479-5876-12-10. doi: 10.1186/1479-5876-12-10 pmid: 24418330
[12]	满杰, 陈莲, 翟晓文, 等. p-AKT/p-mTOR蛋白在儿童Burkitt淋巴瘤中的表达及其与预后的关系[J]. 中华病理学杂志, 2020,49(2):156-161. DOI: 10.3760/cma.j.issn.0529-5807.2020.02.010.
[13]	Hong JY, Hong ME, Choi MK, et al. The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: a clinicopathological study of 262 cases[J]. Ann Oncol, 2014,25(1):182-188. DOI: 10.1093/annonc/mdt530. doi: 10.1093/annonc/mdt530 pmid: 24356628
[14]	Markham A. Idelalisib: first global approval[J]. Drugs, 2014,74(14):1701-1707. DOI: 10.1007/s40265-014-0285-6. doi: 10.1007/s40265-014-0285-6
[15]	Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma[J]. N Engl J Med, 2014,370(11):1008-1018. DOI: 10.1056/NEJMoa1314583. doi: 10.1056/NEJMoa1314583 pmid: 24450858
[16]	Eyre TA, Osborne WL, Gallop-Evans E, et al. Results of a multicentre UK-wide compassionate use programme evaluating the efficacy of idelalisib monotherapy in relapsed, refractory follicular lymphoma[J]. Br J Haematol, 2018,181(4):555-559. DOI: 10.1111/bjh.14665. doi: 10.1111/bjh.14665 pmid: 28342183
[17]	O'Brien SM, Lamanna N, Kipps TJ, et al. A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia[J]. Blood, 2015,126(25):2686-2694. DOI: 10.1182/blood-2015-03-630947. doi: 10.1182/blood-2015-03-630947 pmid: 26472751
[18]	Jones JA, Robak T, Brown JR, et al. Efficacy and safety of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukaemia: an open-label, randomised phase 3 trial[J]. Lancet Haematol, 2017,4(3):e114-e126. DOI: 10.1016/s2352-3026(17)30019-4. doi: 10.1016/S2352-3026(17)30019-4 pmid: 28257752
[19]	Gopal AK, Fanale MA, Moskowitz CH, et al. Phase Ⅱ study of idelalisib, a selective inhibitor of PI3Kδ, for relapsed/refractory classical Hodgkin lymphoma[J]. Ann Oncol, 2017,28(5):1057-1063. DOI: 10.1093/annonc/mdx028. doi: 10.1093/annonc/mdx028 pmid: 28327905
[20]	Dreyling M, Morschhauser F, Bouabdallah K, et al. Phase Ⅱ study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma[J]. Ann Oncol, 2017,28(9):2169-2178. DOI: 10.1093/annonc/mdx289. doi: 10.1093/annonc/mdx289 pmid: 28633365
[21]	Dreyling M, Santoro A, Mollica L, et al. Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma[J]. J Clin Oncol, 2017,35(35):3898-3905. DOI: 10.1200/jco.2017.75.4648. doi: 10.1200/JCO.2017.75.4648 pmid: 28976790
[22]	Markham A. Copanlisib: first global approval[J]. Drugs, 2017,77(18):2057-2062. DOI: 10.1007/s40265-017-0838-6. doi: 10.1007/s40265-017-0838-6 pmid: 29127587
[23]	Dong S, Guinn D, Dubovsky JA, et al. IPI-145 antagonizes intrinsic and extrinsic survival signals in chronic lymphocytic leukemia cells[J]. Blood, 2014,124(24):3583-3586. DOI: 10.1182/blood-2014-07-587279. doi: 10.1182/blood-2014-07-587279
[24]	Flinn IW, Miller CB, Ardeshna KM, et al. DYNAMO: a phase Ⅱ study of duvelisib (IPI-145) in patients with refractory indolent non-Hodgkin lymphoma[J]. J Clin Oncol, 2019,37(11):912-922. DOI: 10.1200/jco.18.00915. doi: 10.1200/JCO.18.00915 pmid: 30742566
[25]	Flinn IW, Hillmen P, Montillo M, et al. The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL[J]. Blood, 2018,132(23):2446-2455. DOI: 10.1182/blood-2018-05-850461. doi: 10.1182/blood-2018-05-850461 pmid: 30287523
[26]	Horwitz SM, Koch R, Porcu P, et al. Activity of the PI3K-δ, γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma[J]. Blood, 2018,131(8):888-898. DOI: 10.1182/blood-2017-08-802470. doi: 10.1182/blood-2017-08-802470 pmid: 29233821
[27]	Wang HQ, Jiang WQ, Li S, et al. Safety and efficacy of TQ-B3525, a novel and selective oral PI3Kα/δ inhibitor, in Chinese patients with advanced malignancies: a phase Ⅰ dose-escalation and expansion trial [C/OL]//AACR Annual Meeting 2020: Session VCTPL04-Immunotherapy clinical trials 2. America, 2020[2020-06-15]. https://asco.confex.com/asco/2020/sci/papers/viewonly.cgi?password=862463&username=309305.