Genetic heterogeneity of <i>KRAS</i>-mutated NSCLC: Co-occurrence of potentially targetable aberrations and evolutionary background.

Scheffler, Matthias; Ihle, Michaela A.; Hein, Rebecca; Merkelbach‐Bruse, Sabine; Braegelmann, Johannes; Scheel, Andreas H.; Michels, Sebastian; Ueckeroth, Frank; Eisert, Anna; Gogl, Leonie; Frank, Rieke; Fischer, Rieke; Koleczko, Sophia; Schaepers, Carsten; Kostenko, Anna; Kron, Florian; Hellmich, Martin; Sos, Martin L.; Buettner, Reinhard; Wolf, Juergen

doi:10.1200/jco.2016.34.15_suppl.9018

Cited by 8 publications

(8 citation statements)

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“…This model may, however, change as technology evolves, as newer ultrasensitive methods have shown co-occurrence of driver oncogenes, including KRAS, in subpopulations within tumors that previously had not been detected by less sensitive methods. 105,106 7. Expert Consensus Opinion.-MET molecular testing is not indicated as a routine stand-alone assay outside the context of a clinical trial.…”

Section: Expert Consensusmentioning

confidence: 99%

Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology

Lindeman

Cagle²,

Aisner³

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

852

1,131

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- The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes ( ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to "rule in" targetable mutations when tissue is limited or hard to obtain.

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Section: Expert Consensusmentioning

confidence: 99%

Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology

Lindeman

Cagle²,

Aisner³

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

852

1,131

View full text Add to dashboard Cite

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“…Concomitant mutations in KRAS and either STK11 or KEAP1 were associated with shorter survival [35]. Additional coexisting mutations were identified in a similar study of 4,507 patients, including genomic alterations in MET, FGFR1, HER2, PIK3CA, DDR2, PTEN, CTNNB1, BRAF, and EGFR [36].…”

Section: Implications Of Concurrent Mutationsmentioning

confidence: 78%

Targeting the KRAS Pathway in Non-Small Cell Lung Cancer

et al. 2016

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Lung cancer remains the leading cause of cancer‐related deaths worldwide. However, significant progress has been made individualizing therapy based on molecular aberrations (e.g., EGFR, ALK) and pathologic subtype. KRAS is one of the most frequently mutated genes in non‐small cell lung cancer (NSCLC), found in approximately 30% of lung adenocarcinomas, and is thus an appealing target for new therapies. Although no targeted therapy has yet been approved for the treatment of KRAS‐mutant NSCLC, there are multiple potential therapeutic approaches. These may include direct inhibition of KRAS protein, inhibition of KRAS regulators, alteration of KRAS membrane localization, and inhibition of effector molecules downstream of mutant KRAS. This article provides an overview of the KRAS pathway in lung cancer and related therapeutic strategies under investigation. Implications for Practice: The identification of oncogene‐addicted cancers and specific inhibitors has revolutionized non‐small cell lung cancer (NSCLC) treatment and outcomes. One of the most commonly mutated genes in adenocarcinoma is KRAS, found in approximately 30% of lung adenocarcinomas, and thus it is an appealing target for new therapies. This review provides an overview of the KRAS pathway and related targeted therapies under investigation in NSCLC. Some of these agents may play a key role in KRAS‐mutant NSCLC treatment in the future.

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“…A critical next step in the study of patients with advanced KRAS mutant NSCLC will be to validate the current observations in additional data sets and explore KRAS molecular contextual signatures, seeking to align them with the kind of specific clinical syndromes we have begun to describe here 13,14 . Such an approach will then lead to additional research attempting to understand why these contexts and behaviors are linked.…”

Section: Discussionmentioning

confidence: 99%

“…Both KRAS-signaling independence and variable dependence on downstream MEK/ERK, PI3K, and RAL signaling have been identified in vitro in KRAS mutant cell lines 11,12 . Recently, with the introduction of routine genomic profiling platforms into the clinic, the broad range of coincident mutations in patients with KRAS mutant NSCLC has been described that may have prognostic significance 13,14 .…”

Section: Introductionmentioning

confidence: 99%

First-line Chemotherapy Responsiveness and Patterns of Metastatic Spread Identify Clinical Syndromes Present Within Advanced KRAS Mutant Non–Small-cell Lung Cancer With Different Prognostic Significance

Iams

Shyr

et al. 2018

Clinical Lung Cancer

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Genetic heterogeneity of KRAS-mutated NSCLC: Co-occurrence of potentially targetable aberrations and evolutionary background.

Cited by 8 publications

References 0 publications

Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology

Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology

Targeting the KRAS Pathway in Non-Small Cell Lung Cancer

First-line Chemotherapy Responsiveness and Patterns of Metastatic Spread Identify Clinical Syndromes Present Within Advanced KRAS Mutant Non–Small-cell Lung Cancer With Different Prognostic Significance

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