Mutations of the catalytic subunit a of PI3K (PIK3CA) in erlotinib-treated non-small cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) mutations.

Carcereny, Enric; Molina, Matias; Sánchez, José Javier; Bertrán-Alamillo, Jordi; Mayo, Carlos A.; Aldeguer, Erika; Capitan, Ana Gimenez; Yeste, Zaira; Costa, Carlota; Benlloch, Susana; Martinez, Andrés; Bugés, Cristina; Bosch, Joaquim; Isla, D.; Dómine, Manuel; Provencio, Mariano; Sanchez, J. M.; Camps, Carlos; Tarón, Miquel; Rosell, R.

doi:10.1200/jco.2011.29.15_suppl.7588

Cited by 7 publications

(7 citation statements)

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“…These frequencies are very close to those previously reported in white patients. 6,7,[15][16][17][18][23][24][25] The relationship between the clinical characteristics of patients and their tumor mutational status also corresponds to previously published results. [12][13][14][15]17,18,38 In our study, EGFR mutations were more frequently found in adenocarcinoma samples, women, and nonsmokers.…”

Section: Discussionsupporting

confidence: 80%

“…28 Mutations in PIK3CA are reported in 4% to 5% of NSCLC patients. 15,16,25 Recently, it was shown that the occurrence of PIK3CA mutations in EGFR mutation-positive tumors increases acquired resistance to EGFR-TKIs. 29 However, further research is required to determine the extent to which these mutations may affect treatment.…”

mentioning

confidence: 99%

“…[12][13][14] Mutations in KRAS and other downstream effectors of the EGFR-pathway, such as BRAF and PIK3CA, have also been identified in NSCLC patients. 15,16 KRAS gene mutations are associated with resistance to EGFR-TKIs and occur in 8% to 16% of NSCLCs, which are increased in patients with adenocarcinomas, men, and smokers. 15,[17][18][19][20][21][22] Mutations in BRAF, which are reported in 0% to 3% of NSCLC patients, 15,[23][24][25] predict a clinical response to EGFR-TKIs.…”

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confidence: 99%

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Sensitive Genotyping of Somatic Mutations in the EGFR, KRAS, PIK3CA, BRAF Genes from NSCLC Patients Using Hydrogel Biochips

Emelyanova

Arkhipova

Мазуренко

et al. 2015

Applied Immunohistochemistry &Amp; Molecular Morphology

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Targeted inhibitors of the epidermal growth factor receptor (EGFR) are used for the treatment of non-small cell lung cancer (NSCLC). Somatic mutations in the EGFR gene and key effectors of the EGFR-signaling pathway (KRAS, BRAF, PIK3CA) are associated with sensitivity to these drugs. We developed a highly sensitive LUNG CANCER (LC)-biochip approach for the detection of the most common EGFR, KRAS, PIK3CA, and BRAF gene mutations. The locked nucleic acid clamp PCR technique was used to increase the sensitivity of the assay, then allele-specific hybridization of a fluorescently labeled target on a biochip was performed. To prove the feasibility of the approach, clinical samples from 112 patients with NSCLC were analyzed. A total of 14 EGFR (12.5%) mutations, 21 (18.8%) KRAS mutations, 12 (10.7%) PIK3CA mutations, and 1 BRAF mutation (0.9%) were found. We compared the results with those from direct sequencing. We detected 50 different mutations by the LC-biochip assay and only 33 of them were found by direct sequencing. To demonstrate that the LC-biochip assay did not give false-positive results, the 17 specimens with discordant results were subjected to locked nucleic acid clamp PCR followed by sequencing. The results of this analysis were identical to the results obtained by the LC-biochip assay indicating that the biochip-based assay was both accurate and reliable. This approach was able to detect approximately 0.5% of mutated alleles in wild-type DNA background. The biochip-based assay is a reliable and inexpensive method for the identification of NSCLC patients, who may respond to a specific targeted therapy.

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Section: Discussionsupporting

confidence: 80%

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confidence: 99%

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confidence: 99%

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Sensitive Genotyping of Somatic Mutations in the EGFR, KRAS, PIK3CA, BRAF Genes from NSCLC Patients Using Hydrogel Biochips

Emelyanova

Arkhipova

Мазуренко

et al. 2015

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…1) also drives EGFR TKI resistance. PIK3CA mutations can co-occur with EGFR mutations and may portend a poorer response to EGFR TKIs (58-60). In addition, acquired PIK3CA mutations have been detected in a small percentage (∼5%) of EGFR mutant lung cancers with AR to EGFR TKIs (6).…”

Section: Therapeutic Strategies Targeting Alternate Pathwaysmentioning

confidence: 99%

Therapeutic Strategies Utilized in the Setting of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors

Riely

Lovly

2014

Clinical Cancer Research

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Patients with EGFR mutant lung cancer derive significant therapeutic benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs). Unfortunately, acquired resistance is an inevitable consequence of this treatment strategy, with a broad variety of resistance mechanisms including acquired EGFR mutations (e.g., T790M) and activation of bypass signaling pathways, such as MET and HER2. Several therapeutic strategies hypothesized to delay or overcome resistance have been tested in clinical trials, including ‘next-generation’ EGFR TKIs and rational combinations of targeted agents. However, to date, there are no FDA approved therapies for patients with acquired resistance to first-line EGFR TKI therapy. There remains a critical need for more effective and better tailored treatments in this setting in order to match treatments to the individual patient and specific resistance mechanism at hand. In this review, we will discuss known mechanisms of resistance to first-line EGFR TKI therapy and describe previous and ongoing strategies to overcome resistance.

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“…At the CIO Cologne Bonn, these analyses are routinely used as part of extended predictive diagnostics. They are all performed on formalin-fixedparaffin-embeddedtissues(FFPE)andrequire pathwayandleadtothedevelopmentoflungcarcinomaswith predominantlypapillaryorbronchioloalveolargrowthpattern [30].MutationsinPIK3CAoccurinlessthan5%ofpatients withlungcancers [31]butmayalsoleadtolowerresponseto EGFR tyrosine kinase inhibitors [32]. Although less commonly, other EGFR pathway genes, including HER2 and HER4,mayalsobeaffectedbysomaticmutations [33].…”

Section: Current Analyses and Potential Problemsmentioning

confidence: 99%

The Role of Molecular Diagnostics in Cancer Diagnosis and Treatment

Ozretić¹,

Heukamp²,

Odenthal³

et al. 2012

Onkologie

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Mutations of the catalytic subunit a of PI3K (PIK3CA) in erlotinib-treated non-small cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) mutations.

Cited by 7 publications

References 0 publications

Sensitive Genotyping of Somatic Mutations in the EGFR, KRAS, PIK3CA, BRAF Genes from NSCLC Patients Using Hydrogel Biochips

Sensitive Genotyping of Somatic Mutations in the EGFR, KRAS, PIK3CA, BRAF Genes from NSCLC Patients Using Hydrogel Biochips

Therapeutic Strategies Utilized in the Setting of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors

The Role of Molecular Diagnostics in Cancer Diagnosis and Treatment

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