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BIOMARKER:

EML4-ALK L1196M

i
Other names: NBLST3, CD246, Anaplastic Lymphoma Kinase, Anaplastic Lymphoma Kinase (Ki-1), CD246 Antigen, Mutant Anaplastic Lymphoma Kinase, ALK, ALK Receptor Tyrosine Kinase, Anaplastic Lymphoma Receptor Tyrosine Kinase, ALK Tyrosine Kinase Receptor, EML4, EMAP Like 4, Restrictedly Overexpressed Proliferation-Associated Protein, Echinoderm Microtubule-Associated Protein-Like 4, Echinoderm Microtubule Associated Protein Like 4, Ropp 120, C2orf2, EMAP-4, EMAPL4, ROPP120, ELP120
Entrez ID:
1m
Impact of tumor-intrinsic molecular features on survival and acquired tyrosine kinase inhibitor resistance in ALK-positive NSCLC. (PubMed, Cancer Res Commun)
V3 status is also associated with specific patterns of clinically important ALK resistance mutations. These tumor-intrinsic features may inform rational selection and optimization of first-line and consolidative therapy.
Journal
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ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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TP53 mutation • ALK positive • ALK fusion • ALK mutation • EML4-ALK variant 3 • ALK G1202R • ALK I1171N • EML4-ALK L1196M • ALK I1171 • ALK L1196M • EML4-ALK G1202R
8ms
Mechanisms of Acquired Resistance to ALK Inhibitors Using Plasma Sequencing - Preliminary Data from the ATORG004 Study (IASLC-WCLC 2023)
In Cohort 1 (n=21), 15 (71%) pts had progressed on alectinib, 5 (24%) on ceritinib and 1 (5%) on ensartinib. In Cohort 2 (n=18), pts had progressed on crizotinib followed by alectinib (n=9, 50%), ceritinib (n=4, 22%) or brigatinib (n=3, 17%); 2 (11%) pts progressed on crizotinib, then ceritinib followed by alectinib...Of 5 pts with ALK resistance mutations (I1171N, V1180L, L1196M, G1202R, and E1210K) who subsequently received lorlatinib, repeat ctDNA NGS after 2 months demonstrated clearance of ALK resistance mutation(s) in 4/5 (80%) pts (i.e. undetectable on repeat testing)... Resistance mechanisms to ALK inhibitors are heterogenous, including both ALK dependent and independent pathways. DDR and cell cycle gene alterations were commonly detected and may represent previously unreported acquired resistance alterations. Comprehensive ctDNA NGS analysis at progression may help detect novel resistance alterations in patients on ALK inhibitors.
Preclinical • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • KIF5B (Kinesin Family Member 5B) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK12 (Cyclin dependent kinase 12) • CDK6 (Cyclin-dependent kinase 6)
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TP53 mutation • HER-2 amplification • NRAS mutation • HER-2 mutation • MET amplification • ALK rearrangement • FGFR1 amplification • ALK fusion • CDK12 mutation • ALK G1202R • ALK I1171N • EML4-ALK L1196M • ALK I1171 • ALK L1196M • ALK amplification • ALK E1210K • ALK V1180L • EML4-ALK G1202R
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Guardant360® CDx
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Ensacove (ensartinib)
10ms
Discovery of imidazo[1,2-b]pyridazine macrocyclic derivatives as novel ALK inhibitors capable of combating multiple resistant mutants. (PubMed, Bioorg Med Chem Lett)
19 novel imidazo[1,2-b]pyridazine macrocyclic derivatives were designed, synthesized, and tested for their biological activities in an effort to develop ALK inhibitors that would overcome second-generation ALK-TKIs, particularly the G1202R mutation and the lorlatinib-resistant L1196M/G1202R double mutations...This was equally effective to the reference drug Repotrectinib (IC = 40, 164, and 208 nM). The kinase selectivity profile, liver microsome stability test and in vivo pharmacokinetic properties in SD rats of compound O-10 were further evaluated. O-10 was regarded as an effective ALK inhibitor for the treatment of mutations overall.
Journal
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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ALK positive • ALK rearrangement • ALK G1202R • EML4-ALK L1196M • ALK L1196M • EML4-ALK G1202R
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Lorbrena (lorlatinib) • Augtyro (repotrectinib)
1year
Preclinical intracranial activity of NVL-655 in an alectinib-resistant patient-derived model harboring EML4-ALK fusion with G1202R mutation (AACR 2023)
Second- (ceritinib, alectinib, brigatinib, and ensartinib) and third-generation (lorlatinib) ALK TKIs have higher intracranial responses than crizotinib but are still limited by emergence of resistance mutations, most commonly G1202R-containing single and compound mutations. Patient-derived models are widely viewed as among the most disease-relevant models for evaluating new therapies and drug resistance. Using a xenograft model derived from an alectinib-relapsed patient, we showed that NVL-655 had high intracranial activity against brain tumors bearing the ALK G1202R mutation that confers resistance to multiple ALK TKIs. NVL-655 is being evaluated in a Phase 1/2 clinical trial for patients with advanced NSCLC and other solid tumors harboring ALK rearrangement or activating ALK mutation (ALKOVE-1): NCT05384626.
Preclinical
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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ALK positive • ALK rearrangement • EML4-ALK fusion • ALK fusion • ALK mutation • ALK G1202R • EML4-ALK L1196M • ALK L1196M • EML4-ALK G1202R
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Ensacove (ensartinib) • NVL-655
over1year
Lorlatinib and compound mutations in ALK+ large-cell neuroendocrine lung carcinoma: a case report. (PubMed, Cold Spring Harb Mol Case Stud)
Despite early progression within 3 mo under crizotinib, a durable response was achieved with alectinib...Another rebiopsy revealed ALK:p.L1196M, but the tumor did not respond to brigatinib or carboplatin/pemetrexed, before stabilization under lorlatinib...Lorlatinib retained efficacy in the heavily pretreated setting, while its upfront use could possibly have prevented the stepwise emergence of compound ALK mutations. Furthermore, the disease course was more aggressive and OS shorter compared to the V2/TP53wt ALK+ lung adenocarcinoma, while crizotinib, ceritinib and brigatinib did not confer the benefit expected according to NGS results, which also underline the need for more potent drugs against ALK in the high-risk setting of neuroendocrine histology.
Journal • Tumor Mutational Burden • IO biomarker
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ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • EML4 (EMAP Like 4) • RB1 (RB Transcriptional Corepressor 1)
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TP53 mutation • TP53 wild-type • TMB-L • ALK mutation • ALK G1202R • EML4-ALK L1196M • ALK L1196M • ALK V1180L • EML4-ALK G1202R • EML4-ALK variant 2 • ALK D1203N
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Xalkori (crizotinib) • carboplatin • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • pemetrexed • Alunbrig (brigatinib)
over1year
Preclinical activity of NVL-655 in patient-derived models of ALK cancers, including those with lorlatinib-resistant G1202R/L1196M compound mutation (AACR-NCI-EORTC 2022)
Five tyrosine kinase inhibitors (TKIs) have been approved for treatment of ALK-positive non-small cell lung cancer (NSCLC), including first- (crizotinib), second- (ceritinib, alectinib, and brigatinib), and third- (lorlatinib) generation therapies. NVL-655 showed activity in diverse patient-derived models of ALK-positive cancers, including ones that exhibited clinical resistance to prior-generation ALK TKIs. The broad preclinical activity of NVL-655 suggests potential utility as a best-in-class therapy for ALK-positive cancer patients.
Preclinical
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STRN (Striatin)
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ALK positive • EML4-ALK fusion • ALK fusion • ALK mutation • ALK G1202R • EML4-ALK L1196M • ALK L1196M • EML4-ALK G1202R • ALK T1151M
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • NVL-655
over1year
Integrated biomarker analysis of brigatinib efficacy in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) refractory to alectinib (ESMO 2022)
Results Of the 133 pts who progressed on alectinib, with or without prior crizotinib or chemotherapy, 131 had evaluable baseline plasma data. The presence of secondary ALK mutations at baseline was associated with a similar ORR (34.5%) and median DoR (5.6 months) and shorter median PFS (3.7 months), with response/clinical benefit observed in pts with G1202R, L1196M, and I1171N ALK secondary mutations. Table: 1009P Brigatinib efficacy parameters a according to baseline ALK mutation status conclusions Brigatinib showed clinically meaningful activity in pts with alectinib-resistant ALK+ NSCLC with or without a detectable ALK fusion and/or secondary mutations.
Clinical
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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ALK positive • EML4-ALK fusion • ALK fusion • ALK mutation • ALK G1202R • ALK I1171N • EML4-ALK L1196M • ALK I1171 • ALK L1196M • EML4-ALK G1202R
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Xalkori (crizotinib) • Alecensa (alectinib) • Alunbrig (brigatinib)
almost2years
Preclinical Activity of NVL-655 in a Patient-Derived NSCLC Model with Lorlatinib-Resistant ALK G1202R/T1151M Mutation (IASLC-WCLC 2022)
Crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib are approved tyrosine kinase inhibitors (TKIs) for ALK-positive NSCLC, but durability of response is partly limited by ALK resistance mutations...Ascites mononuclear cells were isolated by Ficoll centrifugation and cultured in media (DMEM F12 Glutamax, 10% antibiotics/antimycotics, 10% FBS, hydrocortisone, adenine, RockInhibitor, and 1/10 cholera toxin)... NVL-655 has demonstrated activity in many preclinical models bearing ALK compound mutations, including the MR448re (EML4-ALK v3 G1202R/T1151M) model. The potent preclinical activity of NVL-655 suggests potential clinical utility for ALK-positive patients, including those with resistant compound mutations. The MR448re PDC and xenograft are valuable additions to the ALK therapeutic research landscape where there is limited availability of patient-derived models with lorlatinib-resistant ALK compound mutations.
Preclinical
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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ALK positive • ALK rearrangement • EML4-ALK fusion • ALK fusion • ALK mutation • ALK G1202R • ALK G1269A • ALK fusion + ALK G1202R • EML4-ALK L1196M • ALK L1196M • EML4-ALK G1202R • EML4-ALK G1269A • ALK T1151M
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • NVL-655
2years
Real-world circulating tumor DNA analysis depicts resistance mechanism and clonal evolution in ALK inhibitor-treated lung adenocarcinoma patients. (PubMed, ESMO Open)
Sequential postprogression plasma profiling revealed that increased lines of ALK inhibitors can accelerate the accumulation of ALK resistance mutations and may lead to treatment-refractory compound ALK mutations. The selection for optimal first-line TKI is very important to achieve a more efficacious long-term strategy and prevent the emergence of on-target resistance, which may provide guidance for clinical decision making.
Journal • Real-world evidence • Circulating tumor DNA
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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TP53 mutation • ALK positive • ALK fusion • ALK mutation • ALK G1202R • EML4-ALK L1196M • ALK F1174C • ALK L1196M • EML4-ALK G1202R • ALK D1203N • EML4-ALK F1174C
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib)
2years
Acquired TPM3-NTRK1 fusion resistant to larotrectinib in a non-small cell lung cancer with EML4-ALK fusion progressed on lorlatinib (AACR 2022)
Herein, we present an acquired TPM3-NTRK1 fusion resistant to larotrectinib in lung adenocarcinoma with EML4-ALK fusion progressed on lorlatinib.Case Presentation: A 48-year-old male with stage IV adenocarcinoma of lung with metastatic disease of bone was initially treated with carboplatin, pemetrexed, and pembrolizumab...Upon progression of disease (PD), systemic therapy regimen was switched to combination of carboplatin, paclitaxel, and bevacizumab...Subsequently, he was started on alectinib 600 mg twice a day given EML 4-ALK fusion mutation [4.8% of variant allele frequency (VAF)] in circulating tumor DNA (ctDNA) NGS assay...We report the case of acquired TPM3-NTRK1 fusion resistant to larotrectinib and acquired ALK L1196M in lung adenocarcinoma with EML4-ALK fusion progressed on lorlatinib. Further investigations are warranted to explore the mechanism of resistance to ALK TKIs.
PD(L)-1 Biomarker
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ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • EML4 (EMAP Like 4) • TPM3 (Tropomyosin 3) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • ALK positive • EML4-ALK fusion • ALK fusion • ALK mutation • TPM3-NTRK1 fusion • EML4-ALK L1196M • ALK L1196M
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Keytruda (pembrolizumab) • Avastin (bevacizumab) • carboplatin • Vitrakvi (larotrectinib) • paclitaxel • Alecensa (alectinib) • Lorbrena (lorlatinib) • pemetrexed
2years
Longitudinal minimally invasive monitoring of resistance mutations in ALK rearranged lung cancer patients (AACR 2022)
ALK rearrangements are detected in approximately 4% of patients with advanced non-small cell lung cancer (NSCLC), and the tyrosine kinase inhibitors (TKIs) crizotinib, alectinib, brigatinib, ceritinib, and lorlatinib have been approved by the FDA for the treatment of ALK-positive NSCLC. The dPCR method was highly sensitive in detecting gene mutations with low allele frequency. It was also found to be able to monitor variable resistance mutations over time during ALK-TKI treatment. In addition, we found that the appearance of G1202R did not always indicate clinical acquisition of resistance that required drug modification.
Clinical
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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ALK positive • ALK rearrangement • ALK mutation • ALK G1202R • ALK C1156Y • ALK G1269A • ALK I1171T • EML4-ALK L1196M • ALK I1171 • ALK L1196M • ALK L1152R • ALK S1206Y • ALK V1180L • EML4-ALK G1202R • EML4-ALK G1269A • ALK L1196M + ALK C1156Y • EML4-ALK I1171T • EML4-ALK S1206Y
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)
over2years
A new ALK inhibitor overcomes resistance to first- and second-generation inhibitors in NSCLC. (PubMed, EMBO Mol Med)
More than 60% of nonsmall cell lung cancer (NSCLC) patients show a positive response to the first ALK inhibitor, crizotinib, which has been used as the standard treatment for newly diagnosed patients with ALK rearrangement...These preclinical data support XMU-MP-5 as a novel selective ALK inhibitor with high potency and selectivity. XMU-MP-5 holds great promise as a new therapeutic against clinically relevant secondary ALK mutations.
Journal
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EML4 (EMAP Like 4)
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ALK positive • ALK rearrangement • ALK G1202R • EML4-ALK L1196M • ALK L1196M • EML4-ALK G1202R
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Xalkori (crizotinib)
over2years
Clinicopathological features and resistance mechanism in HIP1-ALK-rearranged lung cancer: A multicenter study. (PubMed, Genes Chromosomes Cancer)
One patient who received first-line lorlatinib treatment achieved partial response for >26.5 months...Brigatinib treatment appeared to be effective for a patient who failed crizotinib treatment because of the L1152V/Q1146K mutations, which might be related to increased binding affinity to these mutants...Although HIP1-ALK-rearranged NSCLC appears to initially respond well to ALK-TKIs, crizotinib resistance may be correlated with the AKAP9-BRAF fusion, ALK compound mutations (L1152V/Q1146K), and the ALK L1196M mutation. Larger studies are needed to evaluate the significance of HIP1-ALK-rearranged NSCLC.
Clinical • Journal
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BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4) • HIP1 (Huntingtin Interacting Protein 1)
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BRAF mutation • ALK rearrangement • ALK fusion • ALK mutation • BRAF fusion • EML4-ALK L1196M • ALK L1196M • ALK L1152V
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Xalkori (crizotinib) • Lorbrena (lorlatinib) • Alunbrig (brigatinib)
over2years
A Novel Sequentially Evolved EML4-ALK Variant 3 G1202R/S1206Y Double Mutation In Cis Confers Resistance to Lorlatinib: A Brief Report and Literature Review. (PubMed, JTO Clin Res Rep)
Here, we report, for the first time, a novel, sequentially-evolved EML4-ALK variant 3 G1202R/S1206Y double mutation in cis detected in a patient with ALK-positive NSCLC after disease progression on sequential crizotinib, alectinib, and then lorlatinib. Three-dimensional computer modeling of this double mutation and other G1202R-based double mutations with lorlatinib (ALK G1202R/L1196M, ALK G1202R/F1174C, ALK G1202R/l1198F, ALK G1202R/G1269A) were provided to reveal how these double mutations may confer resistance to lorlatinib through diverse steric hindrances in the ALK kinase domain. In addition, we performed a comprehensive literature review on published acquired double or triple ALK mutations that are resistant to lorlatinib from both patient samples and in vitro mutagenesis experiments.
Review • Journal
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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ALK positive • ALK mutation • EML4-ALK variant 3 • ALK G1202R • ALK G1269A • EML4-ALK L1196M • ALK F1174C • ALK L1196M • ALK S1206Y • EML4-ALK G1202R • EML4-ALK G1269A • EML4-ALK F1174C • EML4-ALK S1206Y
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib)
over2years
One-step polymerase chain reaction-free nanowire-based plasma cell-free DNA assay to detect EML4-ALK fusion and to monitor resistance in lung cancer. (PubMed, Oncologist)
We developed a novel one-step polymerase chain reaction-free nanowire (NW)-based plasma cell-free DNA (cfDNA) assay. In this study, we evaluated the clinical utility of this novel method for the diagnosis of EML4-ALK fusion in advanced non-small cell lung cancer (NSCLC). The NW-based assay and FISH test showed high concordance rate in 99 patients with advanced NSCLC. Serial cfDNA assessment demonstrated this method provided early detection of resistance before radiologic progression during crizotinib treatment. Taken together, plasma cfDNA genotyping by the NW-based cfDNA assay may be useful for the rapid diagnosis of ALK fusion, classifying variants, and early detection of resistance.
Journal • Polymerase Chain Reaction
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EML4 (EMAP Like 4)
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ALK positive • EML4-ALK fusion • ALK fusion • ALK mutation • EML4-ALK L1196M • ALK L1196M
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Xalkori (crizotinib)
over3years
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • KIF5B (Kinesin Family Member 5B) • STRN (Striatin)
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ALK positive • ALK rearrangement • ALK fusion • ALK mutation • ALK G1202R • ALK negative • EML4-ALK L1196M • ALK L1196M • EML4-ALK G1202R
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Guardant360® CDx
over3years
[VIRTUAL] Detection of anaplastic lymphoma kinase (ALK) mutations using circulating tumour DNA (ctDNA) in advanced nonsquamous nonsmall cell lung cancer (nonSqNSCLC) in Asia (ESMO Asia 2020)
Detection rate and distribution of ALK fusion partners are comparable to existing data of tumor ALK testing. Further data on ALK treatment outcomes of patients with detectable ALK fusion on plasma ctDNA is warranted.
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • KIF5B (Kinesin Family Member 5B) • STRN (Striatin)
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ALK positive • ALK rearrangement • ALK fusion • ALK mutation • ALK G1202R • ALK negative • EML4-ALK L1196M • ALK L1196M • EML4-ALK G1202R
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Guardant360® CDx
over3years
[VIRTUAL] Detection of anaplastic lymphoma kinase (ALK) mutations using circulating tumour DNA (ctDNA) in advanced nonsquamous nonsmall cell lung cancer (nonSqNSCLC) in Asia (ESMO Asia 2020)
Detection rate and distribution of ALK fusion partners are comparable to existing data of tumor ALK testing. Further data on ALK treatment outcomes of patients with detectable ALK fusion on plasma ctDNA is warranted.
ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • KIF5B (Kinesin Family Member 5B) • STRN (Striatin)
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ALK positive • ALK rearrangement • ALK fusion • ALK mutation • ALK G1202R • ALK negative • EML4-ALK L1196M • ALK L1196M • EML4-ALK G1202R
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Guardant360® CDx
over3years
Acquired multiple mutations ALK I1171N, L1196M and G1202R mediate lorlatinib resistance in EML4-ALK-rearranged malignant pleural mesothelioma: a case report. (PubMed, Ther Adv Respir Dis)
EML4-ALK rearranged malignant pleural mesothelioma (MPM) is rare and its responses to anaplastic lymphoma kinase (ALK) inhibitors, including alectinib and lorlatinib, remain unexplored. Moreover, our case also revealed acquired mechanisms of lorlatinib resistance mediated by multiple mutations ALK I1171N, L1196M, and G1202R, contributing an incremental step to our understanding of the complexity of acquired resistance mechanisms in sequential ALK inhibitor therapy. The reviews of this paper are available via the supplemental material section.
Clinical • Journal
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ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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ALK rearrangement • ALK G1202R • ALK I1171N • EML4-ALK L1196M • ALK I1171 • ALK L1196M • EML4-ALK G1202R • ALK L1196M + ALK G1202R
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Alecensa (alectinib) • Lorbrena (lorlatinib)
almost4years
[VIRTUAL] Drug resistant PDX models for new drug discovery (AACR-II 2020)
In vivo efficacy results show that this triple mutant NSCLC PDX model was resistant to Erlotinib and AZD9291 and sensitive to the combination of Cetuximab and Brigatinib. We also established CD74-ROS1 fusion and G2032R mutant NSCLC PDX model; EML4-ALK fusion and L1196M mutant NSCLC PDX model; Olaparib resistant Ovarian cancer PDX model; Heceptin resistant gastric PDX model; Rituximab and ABT-199 resistant DLBCL PDX model, and so on. In conclusion, these precious PDX models provide insight into resistance mechanisms as well as serve as models to develop new therapeutics drug candidates that overcome the drug resistant.
PARP Biomarker
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EGFR (Epidermal growth factor receptor) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4) • CD74 (CD74 Molecule)
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EGFR mutation • EML4-ALK fusion • ALK fusion • EGFR C797S • ALK mutation • ROS1 fusion • ROS1 G2032R • EML4-ALK L1196M • ALK L1196M • EGFR T790M + exon 19 deletion
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Venclexta (venetoclax) • Erbitux (cetuximab) • Lynparza (olaparib) • Tagrisso (osimertinib) • erlotinib • Rituxan (rituximab) • Alunbrig (brigatinib)
almost4years
[VIRTUAL] Longitudinal monitoring by next generation sequencing of plasma cell-free DNA in ALK-rearranged non-small cell lung cancer (NSCLC) patients treated with ALK tyrosine kinase inhibitors. (ASCO 2020)
" From April 2015 to July 2019, 92 patients enrolled; 81 (88.0%) received ALK TKI as first-line (crizotinib, n = 59; alectinib, n = 22), 10 (10.9%) received TKI as second-line (alectinib, n = 6; crizotinib, n = 2; ceritinib, n = 1; brigatinib, n = 1), and 1 (1.1%) was treated in third-line (lorlatinib). NGS of cell-free plasma DNA is useful not only for the detection of ALK fusions and resistance mutations but also for assessing prognosis and monitoring the dynamic changes of genomic alterations in ALK+ NSCLC treated with ALK TKI. Research Funding: Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No.NRF-2017M3A9G5060259)Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Kor"
Clinical
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ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4) • TPM3 (Tropomyosin 3)
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ALK rearrangement • EML4-ALK fusion • ALK fusion • ALK mutation • ALK G1202R • ALK G1269A • EML4-ALK L1196M • ALK L1196M • EML4-ALK G1202R • EML4-ALK G1269A • ALK L1196M + ALK G1202R
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Guardant360® CDx
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Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)