8 Matching Annotations
  1. Last 7 days
  2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Untitled document
    8
    1. karim2001khoury 19 Feb 2026
      Osimertinib and selpercatinib efficacy, safety, and resistance in a multicenter, prospectively treated cohort of EGFR-mutant and RET fusion-positive lung cancers

      [Paper-level Aggregated] PMCID: PMC10524391

      Evidence Type(s): Oncogenic, Predictive, Functional, Prognostic

      Justification: Oncogenic: The presence of mutations such as EGFR T790M, L858R, and RET G810S is associated with resistance to targeted therapies, indicating their role in tumor progression and oncogenic potential. Predictive: The identification of specific mutations like EGFR T790M and RET G810S can predict resistance to therapies such as osimertinib, guiding treatment decisions. Functional: The text discusses resistance mutations that affect the function of EGFR and RET kinases, indicating their functional impact on therapeutic engagement and resistance mechanisms. Prognostic: The presence of mutations such as BRAF V600E and KRAS G12S, along with the response rates to treatment, suggests that these mutations may have prognostic implications for patient outcomes.

      Gene→Variant (gene-first): EGFR(1956):C797S KRAS(3845):G12S RET(5979):G810S EGFR(1956):T790M BRAF(673):V600E RET(5979):V804E RET(5979):V804M RET(5979):V804M/E EGFR(1956):L747S EGFR(1956):L858R

      Genes: EGFR(1956) KRAS(3845) RET(5979) BRAF(673)

      Variants: C797S G12S G810S T790M V600E V804E V804M V804M/E L747S L858R

      CIViC paper-level aggregated PMC10524391
    2. karim2001khoury 19 Feb 2026
      Fourteen patients with EGFR-mutant and RET fusion-positive lung cancers who experienced prior progression on osimertinib received osimertinib and selpercatinib. EGFR exon 19 deletions (+-T790M, 86%) and non-KIF5B fusions

      [Paragraph-level] PMCID: PMC10524391 Section: ABSTRACT PassageIndex: 6

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response rate and disease control rate of patients treated with osimertinib and selpercatinib, indicating that the variants mentioned (C797S, G12S, G810S, V600E) are associated with treatment response and resistance mechanisms. Oncogenic: The variants C797S, G12S, G810S, and V600E are described in the context of resistance mechanisms, suggesting their role in tumor development or progression in the setting of lung cancers.

      Gene→Variant (gene-first): 1956:C797S 3845:G12S 5979:G810S 1956:T790M 673:V600E

      Genes: 1956 3845 5979 673

      Variants: C797S G12S G810S T790M V600E

      CIViC paragraph-level PMC10524391 Predictive Oncogenic
    3. karim2001khoury 19 Feb 2026
      Finally, these individual resistance mechanisms commonly co-occurred (Figure 3). In a third of evaluable paired cases, on-target and off-target resistance coexisted: RET V804E + EML4-ALK + STRN-ALK (n=1) and RET V804M +

      [Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 26

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses resistance mechanisms related to specific variants, indicating their correlation with treatment response, particularly in the context of on-target and off-target resistance. Oncogenic: The variants mentioned are associated with resistance mechanisms that contribute to tumor development or progression, as they are involved in co-occurring resistance mechanisms in cancer cases.

      Gene→Variant (gene-first): 1956:C797S 3845:G12S 5979:G810S 673:V600E 5979:V804E 5979:V804M

      Genes: 1956 3845 5979 673

      Variants: C797S G12S G810S V600E V804E V804M

      CIViC paragraph-level PMC10524391 Predictive Oncogenic
    4. karim2001khoury 19 Feb 2026
      Off-target resistance involving receptor tyrosine kinase or MAPK pathway activation was observed in three of six cases (50%). Hotspot mutations were found in two of these cases: BRAF V600E (n=1) and KRAS G12S (n=1). Acqu

      [Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 25

      Evidence Type(s): Oncogenic

      Justification: Oncogenic: The passage discusses hotspot mutations BRAF V600E and KRAS G12S being found in cases of off-target resistance, indicating that these somatic variants contribute to tumor development or progression.

      Gene→Variant (gene-first): 3845:G12S 673:V600E

      Genes: 3845 673

      Variants: G12S V600E

      CIViC paragraph-level PMC10524391 Oncogenic
    5. karim2001khoury 19 Feb 2026
      Presumed loss of the enrolling RET fusion in one or more post-combination therapy progression samples was noted in four of six cases (67%, Figure 2A). In three of these cases, post-progression genomics were limited to a

      [Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 24

      Evidence Type(s): Oncogenic

      Justification: Oncogenic: The passage discusses an acquired RET G810S mutation in the context of tumor progression, indicating that this somatic variant may contribute to tumor development or progression.

      Gene→Variant (gene-first): 5979:G810S

      Genes: 5979

      Variants: G810S

      CIViC paragraph-level PMC10524391 Oncogenic
    6. karim2001khoury 19 Feb 2026
      Resistance mutations that impart steric hindrance to therapeutic EGFR or RET kinase engagement were observed in four of six cases (67%). For EGFR on-target resistance, EGFR C797S was acquired in one patient, and EGFR T79

      [Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 23

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses resistance mutations that affect the engagement of therapeutic EGFR or RET kinases, indicating a correlation with resistance to specific therapies. Oncogenic: The variants mentioned (C797S, T790M, V804M/E, G810S) are described as resistance mutations that contribute to tumor progression by impacting kinase engagement, suggesting their role in oncogenesis.

      Gene→Variant (gene-first): 1956:C797S 5979:G810S 1956:T790M 5979:V804M/E

      Genes: 1956 5979

      Variants: C797S G810S T790M V804M/E

      CIViC paragraph-level PMC10524391 Predictive Oncogenic
    7. karim2001khoury 19 Feb 2026
      All patients were on osimertinib when the acquired RET fusion was identified; 64% (9 patients) were known to have received additional EGFR-directed therapy prior to osimertinib with an earlier generation EGFR TKI (e.g. e

      [Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Predictive, Diagnostic

      Justification: Predictive: The passage discusses the presence of the EGFR T790M mutation in patients who had received prior EGFR-directed therapy, indicating a correlation with treatment response or resistance to osimertinib. Diagnostic: The mention of the EGFR T790M mutation being detectable at the time of study enrollment suggests its role in classifying or confirming the disease status in patients undergoing treatment.

      Gene→Variant (gene-first): 1956:T790M

      Genes: 1956

      Variants: T790M

      CIViC paragraph-level PMC10524391 Predictive Diagnostic
    8. karim2001khoury 19 Feb 2026
      Most tumors (86%, n=12) harbored an EGFR exon 19 deletion (4 of which harbored a concurrent EGFR T790M mutation); the remaining cancers (n=2) both harbored EGFR L858R and EGFR T790M mutations, one of which harbored a con

      [Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Oncogenic, Diagnostic

      Justification: Oncogenic: The passage indicates that the variants L747S, L858R, and T790M are present in tumors, suggesting their role in tumor development or progression. Diagnostic: The presence of specific EGFR mutations, including L747S, L858R, and T790M, is used to classify the tumors, indicating their association with the disease.

      Gene→Variant (gene-first): 1956:L747S 1956:L858R 1956:T790M

      Genes: 1956

      Variants: L747S L858R T790M

      CIViC paragraph-level PMC10524391 Oncogenic Diagnostic
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC10524391/pdf/nihms-1889723.pdf