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Review Article

Targeted Inhibition of the PI3K/Akt/mTOR Signaling Axis: Potential for Sarcoma Therapy

Author(s): Atif Khurshid Wani, Reena Singh, Nahid Akhtar, Ajit Prakash, Eugenie Nepovimova, Patrik Oleksak, Zofia Chrienova, Suliman Alomar, Chirag Chopra* and Kamil Kuca*

Volume 24, Issue 16, 2024

Published on: 23 January, 2024

Page: [1496 - 1520] Pages: 25

DOI: 10.2174/0113895575270904231129062137

Price: $65

Open Access Journals Promotions 2
Abstract

Sarcoma is a heterogeneous group of malignancies often resistant to conventional chemotherapy and radiation therapy. The phosphatidylinositol-3-kinase/ protein kinase B /mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway has emerged as a critical cancer target due to its central role in regulating key cellular processes such as cell growth, proliferation, survival, and metabolism. Dysregulation of this pathway has been implicated in the development and progression of bone sarcomas (BS) and soft tissue sarcomas (STS). PI3K/Akt/mTOR inhibitors have shown promising preclinical and clinical activity in various cancers. These agents can inhibit the activation of PI3K, Akt, and mTOR, thereby reducing the downstream signaling events that promote tumor growth and survival. In addition, PI3K/Akt/mTOR inhibitors have been shown to enhance the efficacy of other anticancer therapies, such as chemotherapy and radiation therapy. The different types of PI3K/Akt/mTOR inhibitors vary in their specificity, potency, and side effect profiles and may be effective depending on the specific sarcoma type and stage. The molecular targeting of PI3K/Akt/mToR pathway using drugs, phytochemicals, nanomaterials (NMs), and microbe-derived molecules as Pan-PI3K inhibitors, selective PI3K inhibitors, and dual PI3K/mTOR inhibitors have been delineated. While there are still challenges to be addressed, the preclinical and clinical evidence suggests that these inhibitors may significantly improve patient outcomes. Further research is needed to understand the potential of these inhibitors as sarcoma therapeutics and to continue developing more selective and effective agents to meet the clinical needs of sarcoma patients.

Keywords: Sarcoma, biomarkers, FDA approved drugs, PI3K/Akt/mToR inhibitors, phytochemicals, nanomaterials.

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[1]
Sbaraglia, M.; Bellan, E.; Dei Tos, A.P. The 2020 WHO classification of soft tissue tumours: News and perspectives. Pathologica, 2020, 113(2), 70-84.
[http://dx.doi.org/10.32074/1591-951X-213] [PMID: 33179614]
[2]
Raza, S.H.A.; Pant, S.D.; Wani, A.K.; Mohamed, H.H.; Khalifa, N.E.; Almohaimeed, H.M.; Alshanwani, A.R.; Assiri, R.; Aggad, W.S.; Noreldin, A.E.; Abdelnour, S.A.; Wang, Z.; Zan, L. Krüppel-like factors family regulation of adipogenic markers genes in bovine cattle adipogenesis. Mol. Cell. Probes, 2022, 65, 101850.
[http://dx.doi.org/10.1016/j.mcp.2022.101850] [PMID: 35988893]
[3]
Lee, S.E.; Kim, Y.J.; Kwon, M.J.; Choi, D.I.; Lee, J.; Cho, J.; Seo, S.W.; Kim, S.J.; Shin, Y.K.; Choi, Y-L. High level of CDK4 amplification is a poor prognostic factor in well-differentiated and dedifferentiated liposarcoma. Histol. Histopathol., 2014, 29(1), 127-138.
[http://dx.doi.org/10.14670/HH-29.127] [PMID: 23852861]
[4]
Ricciotti, R.W.; Baraff, A.J.; Jour, G.; Kyriss, M.; Wu, Y.; Liu, Y.; Li, S.C.; Hoch, B.; Liu, Y.J. High amplification levels of MDM2 and CDK4 correlate with poor outcome in patients with dedifferentiated liposarcoma: A cytogenomic microarray analysis of 47 cases. Cancer Genet., 2017, 218-219, 69-80.
[http://dx.doi.org/10.1016/j.cancergen.2017.09.005] [PMID: 29153098]
[5]
Ravi, V.; Patel, S.; Benjamin, R.S. Chemotherapy for soft-tissue sarcomas. Oncology, 2015, 29(1), 43-50.
[PMID: 25592207]
[6]
Ye, F.; Dewanjee, S.; Li, Y.; Jha, N.K.; Chen, Z-S.; Kumar, A. Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer. Mol. Cancer, 2023, 22, 105.
[http://dx.doi.org/10.1186/s12943-023-01805-y] [PMID: 37415164]
[7]
Ayodele, O.; Razak, A.R.A. Immunotherapy in soft-tissue sarcoma. Curr. Oncol., 2020, 27(11), 17-23.
[http://dx.doi.org/10.3747/co.27.5407] [PMID: 32174754]
[8]
Peng, Y.; Wang, Y.; Zhou, C.; Mei, W.; Zeng, C. PI3K/Akt/MTOR pathway and its role in cancer therapeutics: Are we making headway? Front. Oncol., 2022, 12, 819128.
[http://dx.doi.org/10.3389/fonc.2022.819128] [PMID: 35402264]
[9]
Mir, T.G.; Wani, A.K.; Singh, J.; Shukla, S. Therapeutic application and toxicity associated with Crocus sativus (saffron) and its phytochemicals. Pharmacol. Res. -. Modern Chinese Med.,, 2022, 4, 100136.
[http://dx.doi.org/10.1016/j.prmcm.2022.100136]
[10]
Wani, A.K.; Akhtar, N.; Sharma, A.; El-Zahaby, S.A. fighting carcinogenesis with plant metabolites by weakening proliferative signaling and disabling replicative immortality networks of rapidly dividing and invading cancerous cells. Curr. Drug Deliv., 2022, 12, 122-139.
[PMID: 35422214]
[11]
Ortega, M.A.; Fraile-Martínez, O.; Asúnsolo, Á.; Buján, J.; García-Honduvilla, N.; Coca, S. Signal transduction pathways in breast cancer: The important role of PI3K/Akt/mTOR. J. Oncol., 2020, 2020, 1-11.
[http://dx.doi.org/10.1155/2020/9258396] [PMID: 32211045]
[12]
Wilker, E.; Lu, J.; Rho, O.; Carbajal, S.; Beltrán, L.; DiGiovanni, J. Role of PI3K/Akt signaling in insulin‐like growth factor‐1 (IGF‐1) skin tumor promotion. Mol. Carcinog., 2005, 44(2), 137-145.
[http://dx.doi.org/10.1002/mc.20132] [PMID: 16086373]
[13]
Song, J.H.; Padi, S.K.R.; Luevano, L.A.; Minden, M.D.; DeAngelo, D.J.; Hardiman, G.; Ball, L.E.; Warfel, N.A.; Kraft, A.S. Insulin receptor substrate 1 is a substrate of the Pim protein kinases. Oncotarget, 2016, 7(15), 20152-20165.
[http://dx.doi.org/10.18632/oncotarget.7918] [PMID: 26956053]
[14]
Aziz, A.; Farid, S.; Qin, K.; Wang, H.; Liu, B. PIM kinases and their relevance to the PI3K/AKT/mTOR pathway in the regulation of ovarian cancer. Biomolecules, 2018, 8(1), 7.
[http://dx.doi.org/10.3390/biom8010007] [PMID: 29401696]
[15]
Kyriazoglou, A.; Gkaralea, L.; Kotsantis, I.; Anastasiou, M.; Pantazopoulos, A.; Prevezanou, M.; Chatzidakis, I.; Kavourakis, G.; Economopoulou, P.; Nixon, I.; Psyrri, A. Tyrosine kinase inhibitors in sarcoma treatment (Review). Oncol. Lett., 2022, 23(6), 183.
[http://dx.doi.org/10.3892/ol.2022.13303] [PMID: 35527786]
[16]
Dibble, C.C.; Manning, B.D. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat. Cell Biol., 2013, 15(6), 555-564.
[http://dx.doi.org/10.1038/ncb2763] [PMID: 23728461]
[17]
Wani, A.K.; Akhtar, N.; Mir, T.G.; Singh, R.; Jha, P.K.; Mallik, S.K.; Sinha, S.; Tripathi, S.K.; Jain, A.; Jha, A.; Devkota, H.P.; Prakash, A. Targeting apoptotic pathway of cancer cells with phytochemicals and plant-based nanomaterials. Biomolecules, 2023, 13(2), 194.
[http://dx.doi.org/10.3390/biom13020194] [PMID: 36830564]
[18]
Fusco, N.; Sajjadi, E.; Venetis, K.; Gaudioso, G.; Lopez, G.; Corti, C.; Guerini Rocco, E.; Criscitiello, C.; Malapelle, U.; Invernizzi, M. PTEN alterations and their role in cancer management: Are we making headway on precision medicine? Genes, 2020, 11(7), 719.
[http://dx.doi.org/10.3390/genes11070719] [PMID: 32605290]
[19]
Arcaro, A.; Guerreiro, A. The phosphoinositide 3-kinase pathway in human cancer: Genetic alterations and therapeutic implications. Curr. Genomics, 2007, 8(5), 271-306.
[http://dx.doi.org/10.2174/138920207782446160] [PMID: 19384426]
[20]
Perry, J.A.; Kiezun, A.; Tonzi, P.; Van Allen, E.M.; Carter, S.L.; Baca, S.C.; Cowley, G.S.; Bhatt, A.S.; Rheinbay, E.; Pedamallu, C.S.; Helman, E.; Taylor-Weiner, A.; McKenna, A.; DeLuca, D.S.; Lawrence, M.S.; Ambrogio, L.; Sougnez, C.; Sivachenko, A.; Walensky, L.D.; Wagle, N.; Mora, J.; de Torres, C.; Lavarino, C.; Dos Santos Aguiar, S.; Yunes, J.A.; Brandalise, S.R.; Mercado-Celis, G.E.; Melendez-Zajgla, J.; Cárdenas-Cardós, R.; Velasco-Hidalgo, L.; Roberts, C.W.M.; Garraway, L.A.; Rodriguez-Galindo, C.; Gabriel, S.B.; Lander, E.S.; Golub, T.R.; Orkin, S.H.; Getz, G.; Janeway, K.A. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc. Natl. Acad. Sci., 2014, 111(51), E5564-E5573.
[http://dx.doi.org/10.1073/pnas.1419260111] [PMID: 25512523]
[21]
Zając, A.; Król, S.K.; Rutkowski, P.; Czarnecka, A.M. Biological heterogeneity of chondrosarcoma: From (Epi) genetics through stemness and deregulated signaling to immunophenotype. Cancers, 2021, 13(6), 1317.
[http://dx.doi.org/10.3390/cancers13061317] [PMID: 33804155]
[22]
Jiang, Y.; Subbiah, V.; Janku, F.; Ludwig, J.A.; Naing, A.; Benjamin, R.S.; Brown, R.E.; Anderson, P.; Kurzrock, R. Novel secondary somatic mutations in Ewing’s sarcoma and desmoplastic small round cell tumors. PLoS One, 2014, 9(8), e93676.
[http://dx.doi.org/10.1371/journal.pone.0093676] [PMID: 25119929]
[23]
Huang, C.H.; Mandelker, D.; Schmidt-Kittler, O.; Samuels, Y.; Velculescu, V.E.; Kinzler, K.W.; Vogelstein, B.; Gabelli, S.B.; Amzel, L.M. The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science, 2007, 318(5857), 1744-1748.
[http://dx.doi.org/10.1126/science.1150799] [PMID: 18079394]
[24]
Ren, J.; Wang, X.; Zhou, Y.; Yue, X.; Chen, S.; Ding, X.; Zeng, S.; Jiang, X.; Liu, X.; Guo, Q. A novel SERPINE1‐FOSB fusion gene in pseudomyogenic hemangioendothelioma results in activation of intact FOSB and the PI3K‐AKT‐mTOR signaling pathway and responsiveness to sirolimus. J. Dermatol., 2021, 48(12), 1900-1906.
[http://dx.doi.org/10.1111/1346-8138.16158] [PMID: 34580903]
[25]
Wan, H.; Zhang, D.; Hu, W.; Xie, Z.; Du, Q.; Xia, Q.; Wen, T.; Jia, H. Aberrant PTEN, PIK3CA, pMAPK, and TP53 expression in human scalp and face angiosarcoma. Medicine, 2021, 100(30), e26779.
[http://dx.doi.org/10.1097/MD.0000000000026779] [PMID: 34397726]
[26]
Yoon, C.; Lu, J.; Yi, B.C.; Chang, K.K.; Simon, M.C.; Ryeom, S.; Yoon, S.S. PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas. Oncogenesis, 2021, 10(1), 12.
[http://dx.doi.org/10.1038/s41389-020-00300-z] [PMID: 33468992]
[27]
Jin, Z.; Tao, S.; Zhang, C.; Xu, D.; Zhu, Z. KIF20A promotes the development of fibrosarcoma via PI3K-Akt signaling pathway. Exp. Cell Res., 2022, 420(1), 113322.
[http://dx.doi.org/10.1016/j.yexcr.2022.113322] [PMID: 36037925]
[28]
Presneau, N.; Shalaby, A.; Idowu, B.; Gikas, P.; Cannon, S.R.; Gout, I.; Diss, T.; Tirabosco, R.; Flanagan, A.M. Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway. Br. J. Cancer, 2009, 100(9), 1406-1414.
[http://dx.doi.org/10.1038/sj.bjc.6605019] [PMID: 19401700]
[29]
Dewaele, B.; Maggiani, F.; Floris, G.; Ampe, M.; Vanspauwen, V.; Wozniak, A.; Debiec-Rychter, M.; Sciot, R. Frequent activation of EGFR in advanced chordomas. Clin. Sarcoma Res., 2011, 1(1), 4.
[http://dx.doi.org/10.1186/2045-3329-1-4] [PMID: 22613809]
[30]
Schuetz, A.N.; Rubin, B.P.; Goldblum, J.R.; Shehata, B.; Weiss, S.W.; Liu, W.; Wick, M.R.; Folpe, A.L. Intercellular junctions in Ewing sarcoma/primitive neuroectodermal tumor: Additional evidence of epithelial differentiation. Mod. Pathol., 2005, 18(11), 1403-1410.
[http://dx.doi.org/10.1038/modpathol.3800435] [PMID: 15920547]
[31]
Trautmann, M.; Cyra, M.; Isfort, I.; Jeiler, B.; Krüger, A.; Grünewald, I.; Steinestel, K.; Altvater, B.; Rossig, C.; Hafner, S.; Simmet, T.; Becker, J.; Åman, P.; Wardelmann, E.; Huss, S.; Hartmann, W. Phosphatidylinositol-3-kinase (PI3K)/Akt signaling is functionally essential in myxoid liposarcoma. Mol. Cancer Ther., 2019, 18(4), 834-844.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-0763] [PMID: 30787173]
[32]
Cuppens, T.; Annibali, D.; Coosemans, A.; Trovik, J.; ter Haar, N.; Colas, E.; Garcia-Jimenez, A.; Van de Vijver, K.; Kruitwagen, R.P.M.; Brinkhuis, M.; Zikan, M.; Dundr, P.; Huvila, J.; Carpén, O.; Haybaeck, J.; Moinfar, F.; Salvesen, H.B.; Stukan, M.; Mestdagh, C.; Zweemer, R.P.; Massuger, L.F.; Mallmann, M.R.; Wardelmann, E.; Mints, M.; Verbist, G.; Thomas, D.; Gommé, E.; Hermans, E.; Moerman, P.; Bosse, T.; Amant, F. Potential targets’ analysis reveals dual PI3K/mTOR pathway inhibition as a promising therapeutic strategy for uterine leiomyosarcomas-an ENITEC Group initiative. Clin. Cancer Res., 2017, 23(5), 1274-1285.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2149] [PMID: 28232476]
[33]
Zhu, B.; Davie, J.K. New insights into signalling-pathway alterations in rhabdomyosarcoma. Br. J. Cancer, 2015, 112(2), 227-231.
[http://dx.doi.org/10.1038/bjc.2014.471] [PMID: 25211658]
[34]
Kilic-Eren, M.; Boylu, T.; Tabor, V. Targeting PI3K/Akt represses hypoxia inducible factor-1α activation and sensitizes rhabdomyosarcoma and ewing’s sarcoma cells for apoptosis. Cancer Cell Int., 2013, 13(1), 36.
[http://dx.doi.org/10.1186/1475-2867-13-36] [PMID: 23590596]
[35]
Friedrichs, N.; Trautmann, M.; Endl, E.; Sievers, E.; Kindler, D.; Wurst, P.; Czerwitzki, J.; Steiner, S.; Renner, M.; Penzel, R.; Koch, A.; Larsson, O.; Tanaka, S.; Kawai, A.; Schirmacher, P.; Mechtersheimer, G.; Wardelmann, E.; Buettner, R.; Hartmann, W. Phosphatidylinositol‐3′‐kinase/AKT signaling is essential in synovial sarcoma. Int. J. Cancer, 2011, 129(7), 1564-1575.
[http://dx.doi.org/10.1002/ijc.25829] [PMID: 21128248]
[36]
Bourcier, K.; Le Cesne, A.; Tselikas, L.; Adam, J.; Mir, O.; Honore, C.; de Baere, T. Basic knowledge in soft tissue sarcoma. Cardiovasc. Intervent. Radiol., 2019, 42(9), 1255-1261.
[http://dx.doi.org/10.1007/s00270-019-02259-w] [PMID: 31236647]
[37]
Criscitiello, C. viale, G.; Curigliano, G.; Goldhirsch, A. Profile of buparlisib and its potential in the treatment of breast cancer: Evidence to date. Breast Cancer, 2018, 10, 23-29.
[http://dx.doi.org/10.2147/BCTT.S134641] [PMID: 29430197]
[38]
Bhat, A.A.; Singh, I.; Tandon, N.; Tandon, R. Structure activity relationship (SAR) and anticancer activity of pyrrolidine derivatives: Recent developments and future prospects (A review). Eur. J. Med. Chem., 2023, 246, 114954.
[http://dx.doi.org/10.1016/j.ejmech.2022.114954] [PMID: 36481599]
[39]
Bhat, A.A.; Wani, A.K.; Mir, T. Introduction to ivermectin; Chem. Biol. Act. Ivermectin, 2023, pp. 1-21.
[40]
Harrison, D.; Gill, J.; Roth, M.; Hingorani, P.; Zhang, W.; Teicher, B.; Earley, E.; Erickson, S.; Gatto, G.; Kurmasheva, R.; Houghton, P.; Smith, M.; Anders Kolb, E.; Gorlick, R. Evaluation of the pan‐class I phosphoinositide 3‐kinase (PI3K) inhibitor copanlisib in the pediatric preclinical testing consortium in vivo models of osteosarcoma. Pediatr. Blood Cancer, 2023, 70(1), e30017.
[http://dx.doi.org/10.1002/pbc.30017] [PMID: 36250964]
[41]
Antonescu, C.R.; Owosho, A.A.; Zhang, L.; Chen, S.; Deniz, K.; Huryn, J.M.; Kao, Y.C.; Huang, S.C.; Singer, S.; Tap, W.; Schaefer, I.M.; Fletcher, C.D. Sarcomas with CIC-rearrangements are a distinct pathologic entity with aggressive outcome. Am. J. Surg. Pathol., 2017, 41(7), 941-949.
[http://dx.doi.org/10.1097/PAS.0000000000000846] [PMID: 28346326]
[42]
Carrabotta, M.; Laginestra, M.A.; Durante, G.; Mancarella, C.; Landuzzi, L.; Parra, A.; Ruzzi, F.; Toracchio, L.; De Feo, A.; Giusti, V.; Pasello, M.; Righi, A.; Lollini, P.L.; Palmerini, E.; Donati, D.M.; Manara, M.C.; Scotlandi, K. Integrated molecular characterization of patient-derived models reveals therapeutic strategies for treating CIC-DUX4 sarcoma. Cancer Res., 2022, 82(4), 708-720.
[http://dx.doi.org/10.1158/0008-5472.CAN-21-1222] [PMID: 34903601]
[43]
Grignani, G.; Le Cesne, A.; Martín-Broto, J. Trabectedin as second-line treatment in advanced soft tissue sarcoma: Quality of life and safety outcomes. Future Oncol., 2022, 18(30s), 13-22.
[http://dx.doi.org/10.2217/fon-2022-0518] [PMID: 36200954]
[44]
Dolly, S.O.; Wagner, A.J.; Bendell, J.C.; Kindler, H.L.; Krug, L.M.; Seiwert, T.Y.; Zauderer, M.G.; Lolkema, M.P.; Apt, D.; Yeh, R.F.; Fredrickson, J.O.; Spoerke, J.M.; Koeppen, H.; Ware, J.A.; Lauchle, J.O.; Burris, H.A., III; de Bono, J.S. Phase I study of apitolisib (GDC-0980), dual phosphatidylinositol-3-kinase and mammalian target of rapamycin kinase inhibitor, in patients with advanced solid tumors. Clin. Cancer Res., 2016, 22(12), 2874-2884.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-2225] [PMID: 26787751]
[45]
Choo, F.; Odintsov, I.; Nusser, K.; Nicholson, K.S.; Davis, L.; Corless, C.L.; Stork, L.; Somwar, R.; Ladanyi, M.; Davis, J.L.; Davare, M.A. Functional impact and targetability of PI3KCA, GNAS, and PTEN mutations in a spindle cell rhabdomyosarcoma with MYOD1 L122R mutation. Molecular Case Studies, 2022, 8(1), a006140.
[http://dx.doi.org/10.1101/mcs.a006140] [PMID: 35012940]
[46]
Piazzi, M.; Bavelloni, A.; Cenni, V.; Salucci, S.; Bartoletti Stella, A.; Tomassini, E.; Scotlandi, K.; Blalock, W.L.; Faenza, I. Combined treatment with PI3K inhibitors BYL-719 and CAL-101 is a promising antiproliferative strategy in human rhabdomyosarcoma cells. Molecules, 2022, 27(9), 2742.
[http://dx.doi.org/10.3390/molecules27092742] [PMID: 35566091]
[47]
Roeker, L.E.; Feldman, T.A.; Soumerai, J.D.; Falco, V.; Panton, G.; Dorsey, C.; Zelenetz, A.D.; Falchi, L.; Park, J.H.; Straus, D.J.; Pena Velasquez, C.; Lebowitz, S.; Fox, Y.; Battiato, K.; Laudati, C.; Thompson, M.C.; McCarthy, E.; Kdiry, S.; Martignetti, R.; Turpuseema, T.; Purdom, M.; Paskalis, D.; Miskin, H.P.; Sportelli, P.; Leslie, L.A.; Mato, A.R. Adding umbralisib and ublituximab (U2) to ibrutinib in patients with CLL: A phase II study of an MRD-driven approach. Clin. Cancer Res., 2022, 28(18), 3958-3964.
[http://dx.doi.org/10.1158/1078-0432.CCR-22-0964] [PMID: 35852793]
[48]
Munoz, J.; Follows, G.A.; Nastoupil, L.J. Copanlisib for the treatment of malignant lymphoma: Clinical experience and future perspectives. Target. Oncol., 2021, 16(3), 295-308.
[http://dx.doi.org/10.1007/s11523-021-00802-9] [PMID: 33687623]
[49]
Horwitz, S.M.; Koch, R.; Porcu, P.; Oki, Y.; Moskowitz, A.; Perez, M.; Myskowski, P.; Officer, A.; Jaffe, J.D.; Morrow, S.N.; Allen, K.; Douglas, M.; Stern, H.; Sweeney, J.; Kelly, P.; Kelly, V.; Aster, J.C.; Weaver, D.; Foss, F.M.; Weinstock, D.M. Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma. Blood, 2018, 131(8), 888-898.
[http://dx.doi.org/10.1182/blood-2017-08-802470] [PMID: 29233821]
[50]
Markham, A. Idelalisib: First global approval. Drugs, 2014, 74(14), 1701-1707.
[http://dx.doi.org/10.1007/s40265-014-0285-6] [PMID: 25187123]
[51]
Liu, M.; Zhang, W.E.; Xing, K.; Zhou, P.; Li, J. Inhibitory effect of PD-1/PD-L1 and blockade immunotherapy in leukemia. Comb. Chem. High Throughput Screen., 2022, 25(9), 1399-1410.
[http://dx.doi.org/10.2174/1574893616666210707101516] [PMID: 34238150]
[52]
Anderson, J.L.; Park, A.; Akiyama, R.; Tap, W.D.; Denny, C.T.; Federman, N. Evaluation of in vitro activity of the class I PI3K inhibitor buparlisib (BKM120) in pediatric bone and soft tissue sarcomas. PLoS One, 2015, 10(9), e0133610.
[http://dx.doi.org/10.1371/journal.pone.0133610] [PMID: 26402468]
[53]
Liu, T-J.; Koul, D.; LaFortune, T.; Tiao, N.; Shen, R.J.; Maira, S-M.; Garcia-Echevrria, C.; Alfred Yung, W.K. NVP-BEZ235, A novel dual PI3K/MTOR inhibitor, elicits multifaceted antitumor activities in human gliomas. Mol. Cancer Ther., 2009, 8, 2204-2210.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0160] [PMID: 19671762]
[54]
Rao, V.K.; Webster, S.; Šedivá, A.; Plebani, A.; Schuetz, C.; Shcherbina, A.; Conlon, N.; Coulter, T.I.; Dalm, V.A.; Trizzino, A. Randomized, placebo-controlled, phase 3 trial of PI3Kδ inhibitor leniolisib for activated PI3Kδ syndrome. Blood, 2022, 2022, 018546.
[http://dx.doi.org/10.1182/blood.2022018546]
[55]
Fukuhara, N.; Suehiro, Y.; Kato, H.; Kusumoto, S.; Coronado, C.; Rappold, E.; Zhao, W.; Li, J.; Gilmartin, A.; Izutsu, K. Parsaclisib in Japanese patients with relapsed or refractory B‐cell lymphoma (CITADEL‐111): A phase Ib study. Cancer Sci., 2022, 113(5), 1702-1711.
[http://dx.doi.org/10.1111/cas.15308] [PMID: 35201656]
[56]
Hanan, E.J.; Braun, M.G.; Heald, R.A.; MacLeod, C.; Chan, C.; Clausen, S.; Edgar, K.A.; Eigenbrot, C.; Elliott, R.; Endres, N.; Friedman, L.S.; Gogol, E.; Gu, X.H.; Thibodeau, R.H.; Jackson, P.S.; Kiefer, J.R.; Knight, J.D.; Nannini, M.; Narukulla, R.; Pace, A.; Pang, J.; Purkey, H.E.; Salphati, L.; Sampath, D.; Schmidt, S.; Sideris, S.; Song, K.; Sujatha-Bhaskar, S.; Ultsch, M.; Wallweber, H.; Xin, J.; Yeap, S.; Young, A.; Zhong, Y.; Staben, S.T. Discovery of GDC-0077 (Inavolisib), a highly selective inhibitor and degrader of mutant PI3Kα. J. Med. Chem., 2022, 65(24), 16589-16621.
[http://dx.doi.org/10.1021/acs.jmedchem.2c01422] [PMID: 36455032]
[57]
Goto, H.; Izutsu, K.; Ennishi, D.; Mishima, Y.; Makita, S.; Kato, K.; Hanaya, M.; Hirano, S.; Narushima, K.; Teshima, T.; Nagai, H.; Ishizawa, K. Zandelisib (ME-401) in Japanese patients with relapsed or refractory indolent non-Hodgkin’s lymphoma: An open-label, multicenter, dose-escalation phase 1 study. Int. J. Hematol., 2022, 116(6), 911-921.
[http://dx.doi.org/10.1007/s12185-022-03450-5] [PMID: 36107394]
[58]
Omeljaniuk, W.J.; Krętowski, R.; Ratajczak-Wrona, W.; Jabłońska, E.; Cechowska-Pasko, M. Novel dual PI3K/mTOR inhibitor, apitolisib (GDC-0980), inhibits growth and induces apoptosis in human glioblastoma cells. Int. J. Mol. Sci., 2021, 22(21), 11511.
[http://dx.doi.org/10.3390/ijms222111511] [PMID: 34768941]
[59]
Hsin, I.L.; Shen, H.P.; Chang, H.Y.; Ko, J.L.; Wang, P.H. Suppression of PI3K/Akt/mTOR/c-Myc/mtp53 positive feedback loop induces cell cycle arrest by dual PI3K/mTOR inhibitor PQR309 in endometrial cancer cell lines. Cells, 2021, 10(11), 2916.
[http://dx.doi.org/10.3390/cells10112916] [PMID: 34831139]
[60]
Xu, Y.; Afify, S.M.; Du, J.; Liu, B.; Hassan, G.; Wang, Q.; Li, H.; Liu, Y.; Fu, X.; Zhu, Z.; Chen, L.; Seno, M. The efficacy of PI3Kγ and EGFR inhibitors on the suppression of the characteristics of cancer stem cells. Sci. Rep., 2022, 12(1), 347.
[http://dx.doi.org/10.1038/s41598-021-04265-w] [PMID: 35013447]
[61]
Liu, C.; Xing, W.; Yu, H.; Zhang, W.; Si, T. ABCB1 and ABCG2 restricts the efficacy of gedatolisib (PF-05212384), a PI3K inhibitor in colorectal cancer cells. Cancer Cell Int., 2021, 21(1), 108.
[http://dx.doi.org/10.1186/s12935-021-01800-7] [PMID: 33593355]
[62]
Liang, C.; Yu, X.; Xiong, N.; Zhang, Z.; Sun, Z.; Dong, Y. Pictilisib enhances the antitumor effect of doxorubicin and prevents tumor-mediated bone destruction by blockade of PI3K/AKT pathway. Front. Oncol., 2021, 10, 615146.
[http://dx.doi.org/10.3389/fonc.2020.615146] [PMID: 33659212]
[63]
Zhu, D.; Dong, J.; Xu, Y.; Zhang, X.; Fu, S.; Liu, W. Omipalisib inhibits esophageal squamous cell carcinoma growth through inactivation of phosphoinositide 3-kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) and ERK signaling. Med. Sci. Monit., 2020, 26, e927106.
[http://dx.doi.org/10.12659/MSM.927106] [PMID: 32804918]
[64]
Zhou, S.; Ma, Y.; Xu, R.; Tang, X. Nanoparticles loaded with gsk1059615 combined with sorafenib inhibited programmed cell death 1 ligand 1 expression by negatively regulating the PI3K/Akt/NF- κ B Pathway, thereby reversing the drug resistance of hepatocellular carcinoma to sorafenib. J. Biomed. Nanotechnol., 2022, 18(3), 693-704.
[http://dx.doi.org/10.1166/jbn.2022.3279] [PMID: 35715918]
[65]
Kater, A.P.; Tonino, S.H.; Spiering, M.; Chamuleau, M.E.D.; Liu, R.; Adewoye, A.H.; Gao, J.; Dreiling, L.; Xin, Y.; Doorduijn, J.K.; Kersten, M.J. Final results of a phase 1b study of the safety and efficacy of the PI3Kδ inhibitor acalisib (GS-9820) in relapsed/refractory lymphoid malignancies. Blood Cancer J., 2018, 8(2), 16.
[http://dx.doi.org/10.1038/s41408-018-0055-x] [PMID: 29434192]
[66]
Ceccarelli, M.; D’Andrea, G.; Micheli, L.; Gentile, G.; Cavallaro, S.; Merlino, G.; Papoff, G.; Tirone, F. Tumor growth in the high frequency medulloblastoma mouse model Ptch1+/−/Tis21KO has a specific activation signature of the PI3K/AKT/mTOR pathway and is counteracted by the pi3k inhibitor MEN1611. Front. Oncol., 2021, 11, 692053.
[http://dx.doi.org/10.3389/fonc.2021.692053] [PMID: 34395258]
[67]
Akhtar, N.; Wani, A.K.; Mir, T-U.G.; Kumar, N.; Mannan, M.A-U. Sapindus mukorossi: Ethnomedicinal uses, phytochemistry, and pharmacological activities. Plant Cell Biotechnol. Mol. Biol., 2021, 300-319.
[68]
Selwal, N.; Rahayu, F.; Herwati, A.; Latifah, E.; Suhara, C.; Suastika, I.B.K.; Mahayu, W.M.; Wani, A.K. Enhancing secondary metabolite production in plants: Exploring traditional and modern strategies. J. Agric. Food Res., 2023, 100702.
[69]
Jang, J.Y. Mechanism of resveratrol-induced programmed cell death and new drug discovery against cancer: A review. Int. J. Mol. Sci., 2022, 23.
[http://dx.doi.org/10.3390/ijms232213689]
[70]
Tong, X.; Pelling, J. Targeting the PI3K/Akt/mTOR axis by apigenin for cancer prevention. Anticancer. Agents Med. Chem., 2013, 13(7), 971-978.
[http://dx.doi.org/10.2174/18715206113139990119] [PMID: 23272913]
[71]
Kiptiyah, K.; Widodo, W.; Ciptadi, G.; Aulanni’am, A.; Widodo, M.A.; Sumitro, S.B. 10-Gingerol as an inducer of apoptosis through HTR1A in cumulus cells: In-vitro and in-silico studies. J. Taibah Univ. Med. Sci., 2017, 12(5), 397-406.
[http://dx.doi.org/10.1016/j.jtumed.2017.05.012] [PMID: 31435270]
[72]
Chen, B.H.; Hsieh, C.H.; Tsai, S.Y.; Wang, C.Y.; Wang, C.C. Anticancer effects of epigallocatechin-3-gallate nanoemulsion on lung cancer cells through the activation of AMP-activated protein kinase signaling pathway. Sci. Rep., 2020, 10(1), 5163.
[http://dx.doi.org/10.1038/s41598-020-62136-2] [PMID: 32198390]
[73]
Paulraj, F.; Abas, F.H.; Lajis, N.; Othman, I.; Naidu, R. Molecular pathways modulated by curcumin analogue, diarylpentanoids in cancer. Biomolecules, 2019, 9(7), 270.
[http://dx.doi.org/10.3390/biom9070270] [PMID: 31295798]
[74]
Gan, L.; Leng, Y.; Min, J.; Luo, X.M.; Wang, F.; Zhao, J. Kaempferol promotes the osteogenesis in rBMSCs via mediation of SOX2/miR-124-3p/PI3K/Akt/mTOR axis. Eur. J. Pharmacol., 2022, 927, 174954.
[http://dx.doi.org/10.1016/j.ejphar.2022.174954] [PMID: 35421359]
[75]
Lewandowski, D.; Szewczyk, A.; Radzka, J.; Dubińska-Magiera, M.; Kazimierczak, W.; Daczewska, M.; Migocka-Patrzałek, M. The natural origins of cytostatic compounds used in rhabdomyosarcoma therapy. Adv. Clin. Exp. Med., 2023, 32(10), 1179-1191.
[http://dx.doi.org/10.17219/acem/161165]
[76]
Zhai, Y.; Jiang, S.; Li, B.; Miao, L.; Wang, J.; Li, S. Potential mechanisms of yanghe decoction in the treatment of soft tissue sarcoma and arteriosclerosis obliterans based on network pharmacology. Chinese Med. Nat. Prod., 2022, 2(2), e77-e88.
[http://dx.doi.org/10.1055/s-0042-1755401]
[77]
Khiewkamrop, P.; Surangkul, D.; Srikummool, M.; Richert, L.; Pekthong, D.; Parhira, S.; Somran, J.; Srisawang, P. Epigallocatechin gallate triggers apoptosis by suppressing de novo lipogenesis in colorectal carcinoma cells. FEBS Open Bio, 2022, 12(5), 937-958.
[http://dx.doi.org/10.1002/2211-5463.13391] [PMID: 35243817]
[78]
Kondo, A.; Takeda, T.; Li, B.; Tsuiji, K.; Kitamura, M.; Wong, T.F.; Yaegashi, N. Epigallocatechin-3-gallate potentiates curcumin’s ability to suppress uterine leiomyosarcoma cell growth and induce apoptosis. Int. J. Clin. Oncol., 2013, 18(3), 380-388.
[http://dx.doi.org/10.1007/s10147-012-0387-7] [PMID: 22350026]
[79]
Guo, L.; Qu, B.; Song, C.; Zhu, S.; Gong, N.; Sun, J. Celastrol attenuates 6-hydroxydopamine-induced neurotoxicity by regulating the miR-146a/PI3K/Akt/mTOR signaling pathways in differentiated rat pheochromocytoma cells. J. Affect. Disord., 2022, 316, 233-242.
[http://dx.doi.org/10.1016/j.jad.2022.08.026] [PMID: 35981627]
[80]
Farhan, M.; Silva, M.; Xingan, X.; Zhou, Z.; Zheng, W. Artemisinin inhibits the migration and invasion in uveal melanoma via inhibition of the PI3K/AKT/mTOR signaling pathway. Oxid. Med. Cell. Longev., 2021, 2021, 1-16.
[http://dx.doi.org/10.1155/2021/9911537] [PMID: 34931134]
[81]
Wang, Z.; Li, Y.; Zhou, F.; Piao, Z.; Hao, J. β elemene enhances anticancer bone neoplasms efficacy of paclitaxel through regulation of GPR124 in bone neoplasms cells. Oncol. Lett., 2018, 16(2), 2143-2150.
[http://dx.doi.org/10.3892/ol.2018.8909] [PMID: 30008912]
[82]
Chan, W.K.; Tan, L.; Chan, K.G.; Lee, L.H.; Goh, B.H. Nerolidol: A sesquiterpene alcohol with multi-faceted pharmacological and biological activities. Molecules, 2016, 21(5), 529.
[http://dx.doi.org/10.3390/molecules21050529] [PMID: 27136520]
[83]
Yu, Y.; Velu, P.; Ma, Y.; Vijayalakshmi, A. Nerolidol induced apoptosis via PI3K/JNK regulation through cell cycle arrest in MG ‐63 osteosarcoma cells. Environ. Toxicol., 2022, 37(7), 1750-1758.
[http://dx.doi.org/10.1002/tox.23522] [PMID: 35357761]
[84]
Fang, Y.; Li, H.; Ji, B.; Cheng, K.; Wu, B.; Li, Z.; Zheng, C.; Hua, H.; Li, D. Renieramycin-type alkaloids from marine-derived organisms: Synthetic chemistry, biological activity and structural modification. Eur. J. Med. Chem., 2021, 210, 113092.
[http://dx.doi.org/10.1016/j.ejmech.2020.113092] [PMID: 33333398]
[85]
Chen, S.; Jin, Z.; Dai, L.; Wu, H.; Wang, J.; Wang, L.; Zhou, Z.; Yang, L.; Gao, W. Aloperine induces apoptosis and inhibits invasion in MG-63 and U2OS human osteosarcoma cells. Biomed. Pharmacother., 2018, 97, 45-52.
[http://dx.doi.org/10.1016/j.biopha.2017.09.066] [PMID: 29080457]
[86]
Shinji, S.; Nakamura, S.; Nihashi, Y.; Umezawa, K.; Takaya, T. Berberine and palmatine inhibit the growth of human rhabdomyosarcoma cells. Biosci. Biotechnol. Biochem., 2020, 84(1), 63-75.
[http://dx.doi.org/10.1080/09168451.2019.1659714] [PMID: 31462179]
[87]
Grohar, P.J.; Helman, L.J. Prospects and challenges for the development of new therapies for Ewing sarcoma. Pharmacol. Ther., 2013, 137(2), 216-224.
[http://dx.doi.org/10.1016/j.pharmthera.2012.10.004] [PMID: 23085431]
[88]
Zhou, J.; Huang, Z.; Ni, X.; Lv, C. Piperlongumine induces apoptosis and G2/M phase arrest in human osteosarcoma cells by regulating ROS/PI3K/Akt pathway. Toxicol. In Vitro, 2020, 65, 104775.
[http://dx.doi.org/10.1016/j.tiv.2020.104775] [PMID: 31987842]
[89]
Zhang, Y.; Sun, S.; Chen, J.; Ren, P.; Hu, Y.; Cao, Z.; Sun, H.; Ding, Y. Oxymatrine induces mitochondria dependent apoptosis in human osteosarcoma MNNG/HOS cells through inhibition of PI3K/Akt pathway. Tumour Biol., 2014, 35(2), 1619-1625.
[http://dx.doi.org/10.1007/s13277-013-1223-z] [PMID: 24078465]
[90]
Li, X.; Yang, Z.; Han, W.; Lu, X.; Jin, S.; Yang, W.; Li, J.; He, W.; Qian, Y. Fangchinoline suppresses the proliferation, invasion and tumorigenesis of human osteosarcoma cells through the inhibition of PI3K and downstream signaling pathways. Int. J. Mol. Med., 2017, 40(2), 311-318.
[http://dx.doi.org/10.3892/ijmm.2017.3013] [PMID: 28586029]
[91]
Zhang, Y.; Li, M.; Zhang, Q.; Wang, Z.; Li, X.; Bao, J.; Zhang, H. Arthpyrone L, a new pyridone alkaloid from a deep‐sea arthrinium sp., inhibits proliferation of MG63 osteosarcoma cells by inducing G0/G1 arrest and apoptosis. Chem. Biodivers., 2021, 18(2), e2000639.
[http://dx.doi.org/10.1002/cbdv.202000639] [PMID: 33427403]
[92]
Frasinariu, O.; Serban, R.; Trandafir, L.M.; Miron, I.; Starcea, M.; Vasiliu, I.; Alisi, A.; Temneanu, O.R. The role of phytosterols in nonalcoholic fatty liver disease. Nutrients, 2022, 14(11), 2187.
[http://dx.doi.org/10.3390/nu14112187] [PMID: 35683987]
[93]
Han, B.; Jiang, L.; Jiang, P.; Zhou, D.; Jia, X.; Li, X.; Ye, X. Daucosterol linolenate from sweet potato suppresses MCF7-Xenograft-tumor growth through regulating PI3K/AKT pathway. Planta Med., 2020, 86(11), 767-775.
[http://dx.doi.org/10.1055/a-1176-1884] [PMID: 32512614]
[94]
Zhang, H.; Song, Y.; Feng, C. Improvement of cerebral ischemia/reperfusion injury by daucosterol palmitate-induced neuronal apoptosis inhibition via PI3K/Akt/mTOR signaling pathway. Metab. Brain Dis., 2020, 35(6), 1035-1044.
[http://dx.doi.org/10.1007/s11011-020-00575-6] [PMID: 32363473]
[95]
Moon, D.O.; Lee, K.J.; Choi, Y.H.; Kim, G.Y. β-Sitosterol-induced-apoptosis is mediated by the activation of ERK and the downregulation of Akt in MCA-102 murine fibrosarcoma cells. Int. Immunopharmacol., 2007, 7(8), 1044-1053.
[http://dx.doi.org/10.1016/j.intimp.2007.03.010] [PMID: 17570321]
[96]
Tsuchiya, H.; Sugimoto, N.; Shirai, T.; Hayashi, K.; Nishida, H.; Ohnari, I.; Takeuchi, A.; Yachie, A.; Tsuchiya, H. Caffeine activates tumor suppressor PTEN in sarcoma cells. Int. J. Oncol., 2011, 39(2), 465-472.
[http://dx.doi.org/10.3892/ijo.2011.1051] [PMID: 21617855]
[97]
Eo, S.H.; Kim, J.H.; Kim, S.J. Induction of G 2/M arrest by berberine via activation of PI3K/Akt and p38 in human chondrosarcoma cell line. Oncol. Res., 2015, 22(3), 147-157.
[http://dx.doi.org/10.3727/096504015X14298122915583] [PMID: 26168133]
[98]
Chetty, C.; Lakka, S.S.; Bhoopathi, P.; Rao, J.S. MMP‐2 alters VEGF expression via αVβ3 integrin‐mediated PI3K/AKT signaling in A549 lung cancer cells. Int. J. Cancer, 2010, 127(5), 1081-1095.
[http://dx.doi.org/10.1002/ijc.25134] [PMID: 20027628]
[99]
Chen, J.; Liu, C.; Yang, Q.Q.; Ma, R.B.; Ke, Y.; Dong, F.; Wu, X.E. Isoliquiritigenin suppresses osteosarcoma U2OS cell proliferation and invasion by regulating the PI3K/Akt signalling pathway. Chemotherapy, 2018, 63(3), 155-161.
[http://dx.doi.org/10.1159/000490151] [PMID: 29936511]
[100]
Gao, K.; Su, Z.; Liu, H.; Liu, Y. RETRACTED: Anti-proliferation and anti-metastatic effects of sevoflurane on human osteosarcoma U2OS and Saos-2 cells. Exp. Mol. Pathol., 2019, 108, 121-130.
[http://dx.doi.org/10.1016/j.yexmp.2019.04.005] [PMID: 30974101]
[101]
Ma, K.; Zhang, C.; Li, W. Gamabufotalin suppressed osteosarcoma stem cells through the TGF-β/periostin/PI3K/AKT pathway. Chem. Biol. Interact., 2020, 331, 109275.
[http://dx.doi.org/10.1016/j.cbi.2020.109275] [PMID: 33010222]
[102]
Meng, Z.J.; Wu, N.; Liu, Y.; Shu, K.J.; Zou, X.; Zhang, R.X.; Pi, C.J.; He, B.C.; Ke, Z.Y.; Chen, L.; Deng, Z.L.; Yin, L.J. Evodiamine inhibits the proliferation of human osteosarcoma cells by blocking PI3K/Akt signaling. Oncol. Rep., 2015, 34(3), 1388-1396.
[http://dx.doi.org/10.3892/or.2015.4084] [PMID: 26135006]
[103]
Yang, J.; Zou, Y.; Jiang, D. Honokiol suppresses proliferation and induces apoptosis via regulation of the miR 21/PTEN/PI3K/AKT signaling pathway in human osteosarcoma cells. Int. J. Mol. Med., 2018, 41(4), 1845-1854.
[http://dx.doi.org/10.3892/ijmm.2018.3433] [PMID: 29393336]
[104]
Krajarng, A.; Nakamura, Y.; Suksamrarn, S.; Watanapokasin, R. α-Mangostin induces apoptosis in human chondrosarcoma cells through downregulation of ERK/JNK and Akt signaling pathway. J. Agric. Food Chem., 2011, 59(10), 5746-5754.
[http://dx.doi.org/10.1021/jf200620n] [PMID: 21446759]
[105]
Zheng, M.; Wu, Y. Piceatannol suppresses proliferation and induces apoptosis by regulation of the microRNA 21/phosphatase and tensin homolog/protein kinase B signaling pathway in osteosarcoma cells. Mol. Med. Rep., 2020, 22(5), 3985-3993.
[http://dx.doi.org/10.3892/mmr.2020.11484] [PMID: 32901863]
[106]
Hwang, Y.P.; Yun, H.J.; Choi, J.H.; Han, E.H.; Kim, H.G.; Song, G.Y.; Kwon, K.; Jeong, T.C.; Jeong, H.G. Suppression of EGF‐induced tumor cell migration and matrix metalloproteinase‐9 expression by capsaicin via the inhibition of EGFR‐mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP‐1 signaling. Mol. Nutr. Food Res., 2011, 55(4), 594-605.
[http://dx.doi.org/10.1002/mnfr.201000292] [PMID: 21462327]
[107]
Miyata, Y.; Sato, T.; Ito, A. Triptolide, a diterpenoid triepoxide, induces antitumor proliferation via activation of c-Jun NH2-terminal kinase 1 by decreasing phosphatidylinositol 3-kinase activity in human tumor cells. Biochem. Biophys. Res. Commun., 2005, 336(4), 1081-1086.
[http://dx.doi.org/10.1016/j.bbrc.2005.08.247] [PMID: 16176806]
[108]
Huang, Y.; Chen, J.; Yang, S.; Tan, T.; Wang, N.; Wang, Y.; Zhang, L.; Yang, C.; Huang, H.; Luo, J.; Luo, X. Cinnamaldehyde inhibits the function of osteosarcoma by suppressing the Wnt/β-Catenin and PI3K/Akt signaling pathways. Drug Des. Devel. Ther., 2020, 14, 4625-4637.
[http://dx.doi.org/10.2147/DDDT.S277160] [PMID: 33154629]
[109]
Wang, Y.; Chen, J.; Huang, Y.; Yang, S.; Tan, T.; Wang, N.; Zhang, J.; Ye, C.; Wei, M.; Luo, J.; Luo, X. Schisandrin B suppresses osteosarcoma lung metastasis in vivo by inhibiting the activation of the Wnt/β catenin and PI3K/Akt signaling pathways. Oncol. Rep., 2022, 47(3), 50.
[http://dx.doi.org/10.3892/or.2022.8261] [PMID: 35029287]
[110]
Zhang, R.X.; Li, Y.; Tian, D.D.; Liu, Y.; Nian, W.; Zou, X.; Chen, Q.Z.; Zhou, L.Y.; Deng, Z.L.; He, B.C. Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/β-catenin signaling in human osteosarcoma cells. Int. J. Oncol., 2016, 49(5), 1973-1982.
[http://dx.doi.org/10.3892/ijo.2016.3701] [PMID: 27665868]
[111]
Zhu, J.; Sun, Y.; Lu, Y.; Jiang, X.; Ma, B.; Yu, L.; Zhang, J.; Dong, X.; Zhang, Q.; Glaucocalyxin, A. Glaucocalyxin A exerts anticancer effect on osteosarcoma by inhibiting GLI1 nuclear translocation via regulating PI3K/Akt pathway. Cell Death Dis., 2018, 9(6), 708.
[http://dx.doi.org/10.1038/s41419-018-0684-9] [PMID: 29899333]
[112]
Gweon, E.J.; Kim, S.J. Resveratrol attenuates matrix metalloproteinase-9 and -2- regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways. Oncol. Rep., 2014, 32(1), 71-78.
[http://dx.doi.org/10.3892/or.2014.3192] [PMID: 24841706]
[113]
Zhang, Y.; Weng, Q.; Han, J.; Chen, J. Alantolactone suppresses human osteosarcoma through the PI3K/AKT signaling pathway. Mol. Med. Rep., 2019, 21(2), 675-684.
[http://dx.doi.org/10.3892/mmr.2019.10882] [PMID: 31974628]
[114]
Huang, H.; Lu, Q.; Yuan, X.; Zhang, P.; Ye, C.; Wei, M.; Yang, C.; Zhang, L.; Huang, Y.; Luo, X.; Luo, J. Andrographolide inhibits the growth of human osteosarcoma cells by suppressing Wnt/β-catenin, PI3K/AKT and NF-κB signaling pathways. Chem. Biol. Interact., 2022, 365, 110068.
[http://dx.doi.org/10.1016/j.cbi.2022.110068] [PMID: 35917943]
[115]
Liu, M.Y.; Liu, F.; Li, Y.J.; Yin, J.N.; Gao, Y.L.; Wang, X.Y.; Yang, C.; Liu, J.G.; Li, H.J. Ginsenoside Rg5 inhibits human osteosarcoma cell proliferation and induces cell apoptosis through PI3K/Akt/mTORC1-Related LC3 autophagy pathway. Oxid. Med. Cell. Longev., 2021, 2021, 1-12.
[http://dx.doi.org/10.1155/2021/5040326] [PMID: 34257801]
[116]
Mickymaray, S.; Alfaiz, F.A.; Paramasivam, A.; Veeraraghavan, V.P.; Periadurai, N.D.; Surapaneni, K.M.; Niu, G. Rhaponticin suppresses osteosarcoma through the inhibition of PI3K-Akt-mTOR pathway. Saudi J. Biol. Sci., 2021, 28(7), 3641-3649.
[http://dx.doi.org/10.1016/j.sjbs.2021.05.006] [PMID: 34220214]
[117]
Bhat, A.A.; Thoker, B.A.; Wani, A.K.; Sheergojri, G.A.; Kaloo, M.A.; Bhat, B.A.; Ahmad Rizvi, S.M.; Rizvi, M. Synthesis and characterization of copper oxide nanoparticles by coprecipitation method: Electronic and antimicrobial properties. Chem. Sci. Eng. Res., 2021, 3(6), 25-29.
[http://dx.doi.org/10.36686/Ariviyal.CSER.2021.03.06.031]
[118]
Bilal Ahmad, T.; Asif, A.B. Atif Khurshid; Masood, A.K.; Gulzar Ahmad, S. Preparation and characterization of SnO2 nanoparticles for antibacterial properties. Nanomat. Chem. Technol., 2020, 1–5, 1-5.
[http://dx.doi.org/10.33805/2690-2575.109]
[119]
Xue, X.; Wang, F.; Liu, X. Emerging functional nanomaterials for therapeutics. J. Mater. Chem., 2011, 21(35), 13107-13127.
[http://dx.doi.org/10.1039/c1jm11401h]
[120]
Benton, J.Z.; Williams, R.J.; Patel, A.; Meichner, K.; Tarigo, J.; Nagata, K.; Pethel, T.D.; Gogal, R.M., Jr Gold nanoparticles enhance radiation sensitization and suppress colony formation in a feline injection site sarcoma cell line, in vitro. Res. Vet. Sci., 2018, 117, 104-110.
[http://dx.doi.org/10.1016/j.rvsc.2017.11.018] [PMID: 29220723]
[121]
Naumann, J.A.; Widen, J.C.; Jonart, L.A.; Ebadi, M.; Tang, J.; Gordon, D.J.; Harki, D.A.; Gordon, P.M. SN-38 conjugated gold nanoparticles activated by ewing sarcoma specific mRNAs exhibit in vitro and in vivo efficacy. Bioconjug. Chem., 2018, 29(4), 1111-1118.
[http://dx.doi.org/10.1021/acs.bioconjchem.7b00774] [PMID: 29412642]
[122]
Chakraborty, B.; Pal, R.; Ali, M.; Singh, L.M.; Shahidur Rahman, D.; Kumar Ghosh, S.; Sengupta, M. Immunomodulatory properties of silver nanoparticles contribute to anticancer strategy for murine fibrosarcoma. Cell. Mol. Immunol., 2016, 13(2), 191-205.
[http://dx.doi.org/10.1038/cmi.2015.05] [PMID: 25938978]
[123]
Sanaei, M.J.; Razi, S.; Pourbagheri-Sigaroodi, A.; Bashash, D. The PI3K/Akt/mTOR pathway in lung cancer; oncogenic alterations, therapeutic opportunities, challenges, and a glance at the application of nanoparticles. Transl. Oncol., 2022, 18, 101364.
[http://dx.doi.org/10.1016/j.tranon.2022.101364] [PMID: 35168143]
[124]
Fu, Y.; He, G.; Liu, Z.; Wang, J.; Li, M.; Zhang, Z.; Bao, Q.; Wen, J.; Zhu, X.; Zhang, C.; Zhang, W. DNA base pairing‐inspired supramolecular nanodrug camouflaged by cancer‐cell membrane for osteosarcoma treatment. Small, 2022, 18(30), 2202337.
[http://dx.doi.org/10.1002/smll.202202337] [PMID: 35780479]
[125]
Demirbolat, G.M.; Altintas, L.; Yilmaz, S.; Degim, I.T. Development of orally applicable, combinatorial drug-loaded nanoparticles for the treatment of fibrosarcoma. J. Pharm. Sci., 2018, 107(5), 1398-1407.
[http://dx.doi.org/10.1016/j.xphs.2018.01.006] [PMID: 29339136]
[126]
Tian, Z.; Dong, S.; Yang, Y.; Gao, S.; Yang, Y.; Yang, J.; Zhang, P.; Wang, X.; Yao, W. Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: A retrospective study. BMC Cancer, 2022, 22(1), 56.
[http://dx.doi.org/10.1186/s12885-022-09176-1] [PMID: 35022029]
[127]
Dodd, R.D.; Scherer, A.; Huang, W.; McGivney, G.R.; Gutierrez, W.R.; Laverty, E.A.; Ashcraft, K.A.; Stephens, V.R.; Yousefpour, P.; Saha, S.; Knepper-Adrian, V.; Floyd, W.; Chen, M.; Ma, Y.; Mastria, E.M.; Cardona, D.M.; Eward, W.C.; Chilkoti, A.; Kirsch, D.G. Tumor subtype determines therapeutic response to chimeric polypeptide nanoparticle-based chemotherapy in Pten -deleted mouse models of sarcoma. Clin. Cancer Res., 2020, 26(18), 5036-5047.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-2597] [PMID: 32718998]
[128]
Wani, A.K.; Akhtar, N.; Sher, F.; Navarrete, A.A.; Américo-Pinheiro, J.H.P. Microbial adaptation to different environmental conditions: Molecular perspective of evolved genetic and cellular systems. Arch. Microbiol., 2022, 204(2), 144.
[http://dx.doi.org/10.1007/s00203-022-02757-5] [PMID: 35044532]
[129]
Wani, A.K.; Chopra, C.; Singh, R.; Ahmad, S.; Américo-Pinheiro, J.H.P. Mining microbial tapestry using high-throughput sequencing and in silico analysis of Trehalose synthase (TreS) derived from hot spring metagenome. Biocatal. Agric. Biotechnol., 2023, 52, 102829.
[http://dx.doi.org/10.1016/j.bcab.2023.102829]
[130]
Dhanjal, D.S.; Singh, S.; Kumar, V.; Ramamurthy, P.C.; Chopra, C.; Wani, A.K.; Singh, R.; Singh, J. Isolation and characterization of cellulase-producing myxobacterial strain from the unique niche of mirgund wetland from the north-western himalayas. J. Appl. Biol. Biotechnol., 2023, 11, 119-125.
[http://dx.doi.org/10.7324/JABB.2023.11514-1]
[131]
Wani, A.K.; Akhtar, N.; Datta, B.; Pandey, J.; Mannan, M.A. Cyanobacteria-derived small molecules: A new class of drugs.In: Volatiles and metabolites of microbes; Elsevier, 2021, pp. 283-303.
[http://dx.doi.org/10.1016/B978-0-12-824523-1.00003-1]
[132]
Bhat, A.A.; Tandon, N.; Singh, I.; Tandon, R. Structure-activity relationship (SAR) and antibacterial activity of pyrrolidine based hybrids: A review. J. Mol. Struct., 2023, 1283, 135175.
[http://dx.doi.org/10.1016/j.molstruc.2023.135175]
[133]
Diwan, D.; Cheng, L.; Usmani, Z.; Sharma, M.; Holden, N.; Willoughby, N.; Sangwan, N.; Baadhe, R.R.; Liu, C.; Gupta, V.K. Microbial Cancer Therapeutics: A Promising Approach; Elsevier, 2021.
[134]
Agrawal, S.; Acharya, D.; Adholeya, A.; Barrow, C.J.; Deshmukh, S.K. Nonribosomal peptides from marine microbes and their antimicrobial and anticancer potential. Front. Pharmacol., 2017, 8, 828.
[http://dx.doi.org/10.3389/fphar.2017.00828] [PMID: 29209209]
[135]
Franco, Y.L.; Vaidya, T.R.; Ait-Oudhia, S. Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer. Breast Cancer, 2018, 10, 131-141.
[136]
Taymaz-Nikerel, H.; Karabekmez, M.E.; Eraslan, S.; Kırdar, B. Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells. Sci. Rep., 2018, 8(1), 13672.
[http://dx.doi.org/10.1038/s41598-018-31939-9] [PMID: 30209405]
[137]
Liu, Y.; Zhou, H.; Ma, X.; Lin, C.; Lu, L.; Liu, D.; Ma, D.; Gao, X.; Qian, X.Y. Prodigiosin inhibits proliferation, migration, and invasion of nasopharyngeal cancer cells. Cell. Physiol. Biochem., 2018, 48(4), 1556-1562.
[http://dx.doi.org/10.1159/000492278] [PMID: 30071520]
[138]
Cassier, P.A.; Dufresne, A.; Blay, J-Y.; Fayette, J. Trabectedin and its potential in the treatment of soft tissue sarcoma. Ther. Clin. Risk Manag., 2008, 4(1), 109-116.
[PMID: 18728699]
[139]
Mogi, T.; Kita, K. Gramicidin S and polymyxins: The revival of cationic cyclic peptide antibiotics. Cell. Mol. Life Sci., 2009, 66(23), 3821-3826.
[http://dx.doi.org/10.1007/s00018-009-0129-9] [PMID: 19701717]
[140]
Liu, S.; Cao, C.; Zhang, Y.; Liu, G.; Ren, W.; Ye, Y.; Sun, T. PI3K/Akt inhibitor partly decreases TNF-α-induced activation of fibroblast-like synoviocytes in osteoarthritis. J. Orthop. Surg. Res., 2019, 14(1), 425.
[http://dx.doi.org/10.1186/s13018-019-1394-4] [PMID: 31829201]
[141]
Hideshima, T.; Catley, L.; Yasui, H.; Ishitsuka, K.; Raje, N.; Mitsiades, C.; Podar, K.; Munshi, N.C.; Chauhan, D.; Richardson, P.G.; Anderson, K.C. Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells. Blood, 2006, 107(10), 4053-4062.
[http://dx.doi.org/10.1182/blood-2005-08-3434] [PMID: 16418332]
[142]
Juricic, P.; Lu, Y.X.; Leech, T.; Drews, L.F.; Paulitz, J.; Lu, J.; Nespital, T.; Azami, S.; Regan, J.C.; Funk, E.; Fröhlich, J.; Grönke, S.; Partridge, L. Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy. Nature Aging, 2022, 2(9), 824-836.
[http://dx.doi.org/10.1038/s43587-022-00278-w] [PMID: 37118497]
[143]
Zhang, C.; Wan, J.; Liu, Q.; Long, F.; Wen, Z.; Liu, Y. METTL3 upregulates COPS5 expression in osteosarcoma in an m6A-related manner to promote osteosarcoma progression. Exp. Cell Res., 2022, 420(2), 113353.
[http://dx.doi.org/10.1016/j.yexcr.2022.113353] [PMID: 36100071]
[144]
Althobaiti, N.A.; Raza, S.H.A. The potential therapeutic role of camel milk exosomes. Ann. Anim. Sci., 2022, 10, 67-91.
[145]
Babichev, Y.; Kabaroff, L.; Datti, A.; Uehling, D.; Isaac, M.; Al-awar, R.; Prakesch, M.; Sun, R.X.; Boutros, P.C.; Venier, R.; Dickson, B.C.; Gladdy, R.A. PI3K/AKT/mTOR inhibition in combination with doxorubicin is an effective therapy for leiomyosarcoma. J. Transl. Med., 2016, 14(1), 67.
[http://dx.doi.org/10.1186/s12967-016-0814-z] [PMID: 26952093]
[146]
Rossetti, A.; Petragnano, F.; Milazzo, L.; Vulcano, F.; Macioce, G.; Codenotti, S.; Cassandri, M.; Pomella, S.; Cicchetti, F.; Fasciani, I.; Antinozzi, C.; Di Luigi, L.; Festuccia, C.; De Felice, F.; Vergine, M.; Fanzani, A.; Rota, R.; Maggio, R.; Polimeni, A.; Tombolini, V.; Gravina, G.L.; Marampon, F. Romidepsin (FK228) fails in counteracting the transformed phenotype of rhabdomyosarcoma cells but efficiently radiosensitizes, in vitro and in vivo, the alveolar phenotype subtype. Int. J. Radiat. Biol., 2021, 97(7), 943-957.
[http://dx.doi.org/10.1080/09553002.2021.1928786] [PMID: 33979259]
[147]
Lien, W.C.; Chen, T.Y.; Sheu, S.Y.; Lin, T.C.; Kang, F.C.; Yu, C.H.; Kuan, T.S.; Huang, B.M.; Wang, C.Y. 7‐hydroxy‐staurosporine, UCN‐01, induces DNA damage response, and autophagy in human osteosarcoma U2‐OS cells. J. Cell. Biochem., 2018, 119(6), 4729-4741.
[http://dx.doi.org/10.1002/jcb.26652] [PMID: 29280173]
[148]
Nesic, K.; Ivanovic, S.; Nesic, V. Fusarial toxins: Secondary metabolites of Fusarium fungi. Rev. Environ. Contam. Toxicol., 2014, 228, 101-120.
[http://dx.doi.org/10.1007/978-3-319-01619-1_5] [PMID: 24162094]
[149]
Yao, P.; Yang, D.; Hu, D. Role of PI3K/AKT pathways in mitomycin-mediated apoptosis of WB-F344 cells. Zhonghua Gan Zang Bing Za Zhi, 2015, 23(3), 200-203.
[http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2015.03.009] [PMID: 25938833]
[150]
Heinilä, L.M.P.; Jokela, J.; Ahmed, M.N.; Wahlsten, M.; Kumar, S.; Hrouzek, P.; Permi, P.; Koistinen, H.; Fewer, D.P.; Sivonen, K. Discovery of varlaxins, new aeruginosin-type inhibitors of human trypsins. Org. Biomol. Chem., 2022, 20(13), 2681-2692.
[http://dx.doi.org/10.1039/D1OB02454J] [PMID: 35293909]
[151]
Thomas, S.; Quinn, B.A.; Das, S.K.; Dash, R.; Emdad, L.; Dasgupta, S.; Wang, X.Y.; Dent, P.; Reed, J.C.; Pellecchia, M.; Sarkar, D.; Fisher, P.B. Targeting the Bcl-2 family for cancer therapy. Expert Opin. Ther. Targets, 2013, 17(1), 61-75.
[http://dx.doi.org/10.1517/14728222.2013.733001] [PMID: 23173842]
[152]
Araki, Y.; Hanaki, Y.; Kita, M.; Hayakawa, K.; Irie, K.; Nokura, Y.; Nakazaki, A.; Nishikawa, T. Total synthesis and biological evaluation of oscillatoxins D, E, and F. Biosci. Biotechnol. Biochem., 2021, 85(6), 1371-1382.
[http://dx.doi.org/10.1093/bbb/zbab042] [PMID: 33851985]
[153]
Chilczuk, T.; Steinborn, C.; Breinlinger, S.; Zimmermann-Klemd, A.M.; Huber, R.; Enke, H.; Enke, D.; Niedermeyer, T.H.J.; Gründemann, C. Hapalindoles from the cyanobacterium hapalosiphon sp. inhibit T cell proliferation. Planta Med., 2020, 86(2), 96-103.
[http://dx.doi.org/10.1055/a-1045-5178] [PMID: 31777053]
[154]
Nakano, K.; Takahashi, S. Current molecular targeted therapies for bone and soft tissue sarcomas. Int. J. Mol. Sci., 2018, 19(3), 739.
[http://dx.doi.org/10.3390/ijms19030739] [PMID: 29510588]
[155]
Liu, Q.; Li, J.; Zheng, H.; Yang, S.; Hua, Y.; Huang, N.; Kleeff, J.; Liao, Q.; Wu, W. Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T. Mol. Cancer, 2023, 22(1), 28.
[http://dx.doi.org/10.1186/s12943-023-01735-9] [PMID: 36750830]
[156]
Paskeh, M.D.A.; Ghadyani, F.; Hashemi, M.; Abbaspour, A.; Zabolian, A.; Javanshir, S.; Razzazan, M.; Mirzaei, S.; Entezari, M.; Goharrizi, M.A.S.B.; Salimimoghadam, S.; Aref, A.R.; Kalbasi, A.; Rajabi, R.; Rashidi, M.; Taheriazam, A.; Sethi, G. Biological impact and therapeutic perspective of targeting PI3K/Akt signaling in hepatocellular carcinoma: Promises and Challenges. Pharmacol. Res., 2023, 187, 106553.
[http://dx.doi.org/10.1016/j.phrs.2022.106553] [PMID: 36400343]
[157]
Hopkins, B.D.; Pauli, C.; Du, X.; Wang, D.G.; Li, X.; Wu, D.; Amadiume, S.C.; Goncalves, M.D.; Hodakoski, C.; Lundquist, M.R.; Bareja, R.; Ma, Y.; Harris, E.M.; Sboner, A.; Beltran, H.; Rubin, M.A.; Mukherjee, S.; Cantley, L.C. Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature, 2018, 560(7719), 499-503.
[http://dx.doi.org/10.1038/s41586-018-0343-4] [PMID: 30051890]
[158]
Fakih, M.G.; Kopetz, S.; Kuboki, Y.; Kim, T.W.; Munster, P.N.; Krauss, J.C.; Falchook, G.S.; Han, S.W.; Heinemann, V.; Muro, K.; Strickler, J.H.; Hong, D.S.; Denlinger, C.S.; Girotto, G.; Lee, M.A.; Henary, H.; Tran, Q.; Park, J.K.; Ngarmchamnanrith, G.; Prenen, H.; Price, T.J. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): A prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol., 2022, 23(1), 115-124.
[http://dx.doi.org/10.1016/S1470-2045(21)00605-7] [PMID: 34919824]

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