PI3K inhibitors are finally coming of age.
PI3K inhibitors are finally coming of age.
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DOI：
10.1038/s41573-021-00209-1
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发表时间：
2021-10
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
作者：
癌症和免疫失调中过度活跃的 PI 3 激酶 (PI3K) 促使人们广泛致力于开发治疗性 PI3K 抑制剂。虽然进展受到耐药性差和耐药性等问题的阻碍，但几种 PI3K 抑制剂现已获得监管部门的批准——用于治疗乳腺癌的 PI3Kα 异构体选择性抑制剂 alpelisib，以及主要针对 B 细胞恶性肿瘤中富含白细胞的 PI3Kδ 的抑制剂。除了针对癌细胞内在 PI3K 活性之外，新出现的证据凸显了 PI3K 抑制剂在癌症免疫治疗中的潜力。本综述总结了有助于 PI3Kα 和 PI3Kδ 抑制剂临床转化的关键发现，强调了经验教训和未来机遇。 PI3K 信号传导是癌症中最常异常激活的途径之一。然而，治疗性PI3K通路抑制剂的开发面临着耐药性差和耐药性等挑战。在这里，Vanhaesebroeck 等人。回顾了理解和治疗性利用 PI3Kα 和 PI3Kδ 生物学的努力，PI3Kα 和 PI3Kδ 是目前批准的 PI3K 抑制剂的关键靶标，强调了经验教训和未来的机会。
Overactive PI 3-kinase (PI3K) in cancer and immune-dysregulation has spurred extensive efforts to develop therapeutic PI3K inhibitors. Although progress has been hampered by issues such as poor drug tolerance and drug resistance, several PI3K inhibitors have now received regulatory approval – the PI3Kα isoform-selective inhibitor alpelisib for the treatment of breast cancer, and inhibitors mainly aimed at the leukocyte-enriched PI3Kδ in B-cell malignancies. In addition to targeting cancer-cell intrinsic PI3K activity, emerging evidence highlights the potential of PI3K inhibitors in cancer immunotherapy. This review summarises key discoveries aiding the clinical translation of PI3Kα and PI3Kδ inhibitors, highlighting lessons learned and future opportunities. PI3K signalling is one of the most frequently aberrantly-activated pathways in cancer. However, the development of therapeutic PI3K pathway inhibitors has faced challenges including poor drug tolerance and drug resistance. Here, Vanhaesebroeck et al. review efforts to understand and therapeutically exploit the biology of PI3Kα and PI3Kδ — the key targets of currently approved PI3K inhibitors, highlighting lessons learned and future opportunities.
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肿瘤微环境中的磷酸肌醇3-激酶信号传导：在用PI3K抑制剂治疗慢性淋巴细胞性白血病时，我们需要考虑什么？
影响因子：
7.3
作者：
Aydin E;Faehling S;Saleh M;Llaó Cid L;Seiffert M;Roessner PM
通讯作者：
Roessner PM
DOI：
10.1084/jem.20180010
发表时间：
2018-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Avery DT;Kane A;Nguyen T;Lau A;Nguyen A;Lenthall H;Payne K;Shi W;Brigden H;French E;Bier J;Hermes JR;Zahra D;Sewell WA;Butt D;Elliott M;Boztug K;Meyts I;Choo S;Hsu P;Wong M;Berglund LJ;Gray P;O'Sullivan M;Cole T;Holland SM;Ma CS;Burkhart C;Corcoran LM;Phan TG;Brink R;Uzel G;Deenick EK;Tangye SG
通讯作者：
Tangye SG
DOI：
10.1126/science.1243292
发表时间：
2013-11-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Angulo I;Vadas O;Garçon F;Banham-Hall E;Plagnol V;Leahy TR;Baxendale H;Coulter T;Curtis J;Wu C;Blake-Palmer K;Perisic O;Smyth D;Maes M;Fiddler C;Juss J;Cilliers D;Markelj G;Chandra A;Farmer G;Kielkowska A;Clark J;Kracker S;Debré M;Picard C;Pellier I;Jabado N;Morris JA;Barcenas-Morales G;Fischer A;Stephens L;Hawkins P;Barrett JC;Abinun M;Clatworthy M;Durandy A;Doffinger R;Chilvers ER;Cant AJ;Kumararatne D;Okkenhaug K;Williams RL;Condliffe A;Nejentsev S
通讯作者：
Nejentsev S
影响因子：
11.2
作者：
Ahmad, Shamim;Abu-Eid, Rasha;Khleif, Samir N.
通讯作者：
Khleif, Samir N.
影响因子：
64.8
作者：
Ali, K;Bilancio, A;Vanhaesebroeck, B
通讯作者：
Vanhaesebroeck, B