PIK3CA mutations in advanced cancers: characteristics and outcomes.
PIK3CA mutations in advanced cancers: characteristics and outcomes.
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DOI：
10.18632/oncotarget.716
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Kurzrock R
中科院分区：
文献类型：
--
作者：
Janku F;Wheler JJ;Naing A;Stepanek VM;Falchook GS;Fu S;Garrido-Laguna I;Tsimberidou AM;Piha-Paul SA;Moulder SL;Lee JJ;Luthra R;Hong DS;Kurzrock R
PIK3CA突变在多种癌症中经常被检测到，并且可能预测对PI3K/AKT/mTOR抑制剂的反应。它们是否与其他特征相关仍不清楚。我们分析了90例连续的患有不同晚期肿瘤且具有PIK3CA突变的患者以及180例按肿瘤类型、性别和年龄匹配的野生型PIK3CA对照者的特征和预后，这些患者和对照者均转诊至靶向治疗临床中心。使用基于聚合酶链反应的DNA测序分析PIK3CA和MAPK突变（KRAS、NRAS和BRAF）。最常见的PIK3CA突变是外显子9中的E545K（31/90，34%）、E542K（16/90，18%）以及外显子20中的H1047R（20/90，22%）。与野生型PIK3CA相比，PIK3CA突变与同时存在的KRAS（p = 0.047）和MAPK突变（p = 0.03）相关，但在多变量分析中只有MAPK突变被证实具有独立相关性。PIK3CA突变型和野生型患者的肺、骨、肝和脑转移率相似。在PI3K/AKT/mTOR抑制剂试验中接受治疗的PIK3CA突变患者比接受最佳I期治疗的野生型PIK3CA患者具有更高的部分/完全缓解（PR/CR）率（10/56，18%对12/152，8%；p = 0.045），但无更长的无进展生存期。与接受最佳I期治疗的野生型PIK3CA患者相比，具有H1047R PIK3CA突变的患者使用PI3K/AKT/mTOR抑制剂具有更高的PR/CR率（6/16，38%对12/152，8%；p = 0.003）。总之，多种癌症中的PIK3CA突变与临床特征无关，但与MAPK突变相关。PIK3CA突变，尤其是H1047R，与对PI3K/AKT/mTOR通路抑制剂达到PR/CR相关。
PIK3CA mutations are frequently diagnosed in diverse cancers and may predict response to PI3K/AKT/mTOR inhibitors. It remains unclear whether they are associated with other characteristics. We analyzed characteristics and outcome of 90 consecutive patients with diverse advanced tumors and PIK3CA mutations and 180 wild-type PIK3CA controls matched by tumor type, gender, and age referred to the Clinical Center for Targeted Therapy. PIK3CA and MAPK mutations (KRAS, NRAS, and BRAF) were analyzed using polymerase chain reaction-based DNA sequencing. The most frequent PIK3CA mutations were E545K (31/90, 34%), E542K (16/90, 18%) in exon 9, and H1047R (20/90, 22%) in exon 20. PIK3CA mutations compared to wild-type PIK3CA were associated with simultaneous KRAS (p=0.047) and MAPK mutations (p=0.03), but only MAPK mutations were confirmed as having an independent association in multivariate analysis. Rates of lung, bone, liver and brain metastases were similar in PIK3CA-mutant and wild-type patients. Patients with PIK3CA mutations treated on trials with PI3K/AKT/mTOR inhibitors had a higher partial/complete response (PR/CR) rate than wild-type PIK3CA patients treated with their best phase I therapy (10/56, 18% vs. 12/152, 8%; p=0.045), but not a prolonged progression-free survival. Patients with H1047R PIK3CA mutations had a higher PR/CR rate with PI3K/AKT/mTOR inhibitors compared to wild-type PIK3CA patients treated with their best phase I therapy (6/16, 38% vs. 12/152, 8%; p=0.003). In conclusion, PIK3CA mutations in diverse cancers were not associated with clinical characteristics, but were correlated with MAPK mutations. PIK3CA mutations, especially, H1047R, were associated with attaining a PR/CR to PI3K/AKT/mTOR pathway inhibitors.
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有效使用 PI3K 和 MEK 抑制剂治疗突变型 Kras G12D 和 PIK3CA H1047R 小鼠肺癌。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
20.4
作者：
Ludovini, Vienna;Bianconi, Fortunato;Crino, Lucio
通讯作者：
Crino, Lucio
用PI3K/AKT/MTOR轴抑制剂治疗的晚期癌症患者的PIK3CA突变。
影响因子：
5.7
作者：
Janku F;Tsimberidou AM;Garrido-Laguna I;Wang X;Luthra R;Hong DS;Naing A;Falchook GS;Moroney JW;Piha-Paul SA;Wheler JJ;Moulder SL;Fu S;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
5.7
作者：
Chaft JE;Arcila ME;Paik PK;Lau C;Riely GJ;Pietanza MC;Zakowski MF;Rusch V;Sima CS;Ladanyi M;Kris MG
通讯作者：
Kris MG
DOI：
10.1200/jco.2008.18.6544
发表时间：
2009-03-20
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Ogino S;Nosho K;Kirkner GJ;Shima K;Irahara N;Kure S;Chan AT;Engelman JA;Kraft P;Cantley LC;Giovannucci EL;Fuchs CS
通讯作者：
Fuchs CS