Gene mutations in small-cell lung cancer (SCLC): Results of a panel of 6 genes in a cohort of Italian patients

Bordi, Paola; Tiseo, Marcello; Barbieri, Fausto; Bavieri, Mario; Sartori, Giuliana; Marchetti, Antonio; Buttitta, Fiamma; Bortesi, Beatrice; Ambrosini-Spaltro, Andrea; Gnetti, Letizia; Silini, Enrico Maria; Ardizzoni, Andrea; Rossi, Giulio

doi:10.1016/j.lungcan.2014.10.002

Cited by 30 publications

(31 citation statements)

References 29 publications

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“…While activating mutations in oncogenes signaling through the RAS-RAF-MEK-ERK pathway are rare in SCLC tumors, these mutations have been identified 13–15, 30, 31 . For example, activating mutations in the c-KIT receptor are present in a small percent of human SCLC tumors 15, 32 (Figure 2), and activation of this receptor by its ligand SCF can promote ERK1/2 activity in SCLC cells 33–36 , though in certain contexts SCLC cells respond to SCF binding independently of ERK1/2 37 .…”

Section: Main Textmentioning

confidence: 99%

Is the Canonical RAF/MEK/ERK Signaling Pathway a Therapeutic Target in SCLC?

Cristea

Sage

2016

Journal of Thoracic Oncology

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The activity of the RAF-MEK-ERK signaling pathway is critical for the proliferation of normal and cancerous cells. Oncogenic mutations driving the development of lung adenocarcinoma often activate this signaling pathway. In contrast, pathway activity levels and their biological roles are not well established in small cell lung cancer (SCLC), a fast-growing neuroendocrine lung cancer subtype. Here we discuss the function of the RAF-MEK-ERK kinase pathway and the mechanisms leading to its activation in SCLC cells. In particular, we argue that activation of this pathway may be beneficial to the survival, proliferation and spread of SCLC cells in response to multiple stimuli. We also consider evidence that high levels of RAF-MEK-ERK pathway activity may be detrimental to SCLC tumors, including in part by interfering with their neuroendocrine fate. Based on these observations, we examine when small molecules targeting kinases in the RAF-MEK-ERK pathway may be useful therapeutically in SCLC patients, including in combination with other therapeutic agents.

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Section: Main Textmentioning

confidence: 99%

Is the Canonical RAF/MEK/ERK Signaling Pathway a Therapeutic Target in SCLC?

Cristea

Sage

2016

Journal of Thoracic Oncology

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“…Panel testing on a cohort of Italian patients with SCLC found two patients out of 113 with an EGFR mutation; both were women and never‐smokers. Of the two tumours, one contained an exon 19 deletion and the other harboured an L858R mutation in exon 21 . Other cases reported in the literature have also identified a G719A mutation …”

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confidence: 76%

“…In addition, there are very few reported cases of de novo EGFR mutations occurring in SCLC without mixed SCLC and NSCLC histology or TKI exposure. [6][7][8] We report two cases of SCLC in patients of Asian ethnicity and no smoking history that harbour de novo EGFR mutations detected in tissue biopsies and subsequently assessed in plasma cell-free DNA (cfDNA).…”

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confidence: 99%

“…In these cases, the tumour will often still harbour the original EGFR mutation. In addition, there are very few reported cases of de novo EGFR mutations occurring in SCLC without mixed SCLC and NSCLC histology or TKI exposure …”

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confidence: 99%

“…SCLC is commonly viewed as a smoker's disease but never smokers account for 2–3% of SCLC cases . Two case series reported an incidence of de novo EGFR mutations in SCLC of 1–1.18%, rising to 14% in never smokers . Another case series found that the accumulated smoking dose in patients with an activating mutation was much lower compared to patients with no activating mutation (median pack‐years 30 versus 54 pack years ( P = 0.020)) .…”

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confidence: 99%

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De novo activating epidermal growth factor mutations (EGFR) in small‐cell lung cancer

Thai

Chia

Russell

et al. 2017

Internal Medicine Journal

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In Australia, mutations in epidermal growth factor mutations (EGFR) occur in 15% of patients diagnosed with non-small-cell lung cancer and are found with higher frequency in female, non-smokers of Asian ethnicity. Activating mutations in the EGFR gene are rarely described in SCLC. We present two cases of de novo EGFR mutations in patients with SCLC detected in tissue and in plasma cell free DNA, both of whom were of Asian ethnicity and never-smokers. These two cases add to the growing body of evidence suggesting that screening for EGFR mutations in SCLC should be considered in patients with specific clinical features.

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Characteristics and prognosis of EGFR mutations in small cell lung cancer patients in the NGS era

Xie,

Qiu,

Chen

et al. 2023

Clin Transl Oncol

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Purpose Targeted therapy has not been effective for small cell lung cancer (SCLC) patients. Although some studies have reported on EGFR mutations in SCLC, a systematic investigation into the clinical, immunohistochemical, and molecular characteristics and prognosis of EGFR-mutated SCLCs is lacking. Methods Fifty-seven SCLC patients underwent next-generation sequencing technology, with 11 in having EGFR mutations (group A) and 46 without (group B). Immunohistochemistry markers were assessed, and the clinical features and first-line treatment outcomes of both groups were analyzed. Results Group A consisted primarily of non-smokers (63.6%), females (54.5%), and peripheral-type tumors (54.5%), while group B mainly comprised heavy smokers (71.7%), males (84.8%), and central-type tumors (67.4%). Both groups showed similar immunohistochemistry results and had RB1 and TP53 mutations. When treated with tyrosine kinase inhibitors (TKIs) plus chemotherapy, group A had a higher treatment response rate with overall response and disease control rates of 80% and 100%, respectively, compared to 57.1% and 100% in group B. Group A also had a significantly longer median progression-free survival (8.20 months, 95% CI 6.91–9.49 months) than group B (2.97 months, 95% CI 2.79–3.15), with a significant difference (P = 0.043). Additionally, the median overall survival was significantly longer in group A (16.70 months, 95% CI 1.20–32.21) than in group B (7.37 months, 95% CI 3.85–10.89) (P = 0.016). Conclusion EGFR-mutated SCLCs occurred more frequently in non-smoking females and were linked to prolonged survival, implying a positive prognostic impact. These SCLCs shared immunohistochemical similarities with conventional SCLCs, and both types had prevalent RB1 and TP53 mutations.

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Gene mutations in small-cell lung cancer (SCLC): Results of a panel of 6 genes in a cohort of Italian patients

Cited by 30 publications

References 29 publications

Is the Canonical RAF/MEK/ERK Signaling Pathway a Therapeutic Target in SCLC?

Is the Canonical RAF/MEK/ERK Signaling Pathway a Therapeutic Target in SCLC?

De novo activating epidermal growth factor mutations (EGFR) in small‐cell lung cancer

Characteristics and prognosis of EGFR mutations in small cell lung cancer patients in the NGS era

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