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BIOMARKER:

ALK amplification

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
Entrez ID:
2ms
NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922) (clinicaltrials.gov)
P1, N=65, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date
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ALK fusion • ALK mutation • ALK translocation • ALK amplification
|
Lorbrena (lorlatinib) • cyclophosphamide • topotecan • Neulasta (pegfilgrastim) • Neupogen (filgrastim)
5ms
PROFILE 1013: An Investigational Drug, Crizotinib (PF-02341066), Is Being Studied In Tumors, Except Non-Small Cell Lung Cancer, That Are Positive For Anaplastic Lymphoma Kinase (ALK) (clinicaltrials.gov)
P1b, N=44, Terminated, Pfizer | Active, not recruiting --> Terminated; Termination of further treatment on the study due to the availability of commercial supply or a rollover study (NCT05160922) that will allow active subjects to continue receiving treatment.
Trial termination
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ALK (Anaplastic lymphoma kinase)
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ALK positive • ALK mutation • ALK translocation • ALK amplification
|
Xalkori (crizotinib)
6ms
Examining the Effect of ALK and EGFR Mutations on Survival Outcomes in Surgical Lung Brain Metastasis Patients. (PubMed, Cancers (Basel))
Although the sample size of patients receiving targeted therapies was limited, the study highlighted improved overall survival and progression-free survival rates compared to earlier trials, suggesting advancements in systemic lung metastasis treatment. The study suggests that as more targeted therapies emerge, the prospects for increased overall survival and progression-free survival in lung brain metastasis patients will likely improve.
Journal
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
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EGFR mutation • EGFR amplification • ALK rearrangement • ALK mutation • ALK amplification • EGFR mutation + ALK mutation
6ms
Molecular heterogeneity and co-altered genes in MET-amplified ALK-positive lung cancer: Implications for MET targeted therapy. (PubMed, Lung Cancer)
MET-amplified, ALK + NSCLC often presents with high-level and heterogeneous amplification in tissue, seldom overlaps with ALK mutations, and frequently co-occurs with alterations associated with aggressive tumor biology.
Journal
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • EML4 (EMAP Like 4)
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TP53 mutation • EGFR mutation • ALK positive • MET amplification • EGFR amplification • ALK rearrangement • MYC amplification • MET mutation • ALK amplification • EML4-ALK variant 1
7ms
Genome-guided targeted therapy combination improves survival in patients with advanced EGFR mutation positive NSCLC failing osimertinib (ESMO Asia 2023)
Conclusions The combination of GGTT and osimertinib improves TTF and OS in EGFR mutation positive NSCLC patients failing osimertinib. Future prospective comparative study is warranted.
Clinical • Metastases
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
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BRAF V600E • EGFR mutation • BRAF V600 • MET amplification • ALK rearrangement • RET rearrangement • EGFR positive • ALK amplification • ALK rearrangement + MET amplification
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Tagrisso (osimertinib)
7ms
Prognostic value of ALK overexpression and molecular abnormalities in high-grade serous ovarian carcinoma. (PubMed, Cancer Biomark)
HGSOC harbouring activating ALK mutations might be associated with a better survival, while ALK overexpression and ALK amplification does not impact the prognosis.
Journal • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • BRCA1 (Breast cancer 1, early onset) • GRB7 (Growth Factor Receptor Bound Protein 7) • PRKCA (Protein Kinase C Alpha)
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ALK rearrangement • ALK mutation • ALK translocation • ALK amplification
9ms
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
PROFILE 1013: An Investigational Drug, Crizotinib (PF-02341066), Is Being Studied In Tumors, Except Non-Small Cell Lung Cancer, That Are Positive For Anaplastic Lymphoma Kinase (ALK) (clinicaltrials.gov)
P1b, N=44, Active, not recruiting, Pfizer | Trial completion date: Apr 2023 --> Jul 2023 | Trial primary completion date: Apr 2023 --> Jul 2023
Trial completion date • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK mutation • ALK translocation • ALK amplification
|
Xalkori (crizotinib)
11ms
NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922) (clinicaltrials.gov)
P1, N=65, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Recruiting --> Active, not recruiting
Enrollment closed
|
ALK fusion • ALK mutation • ALK translocation • ALK amplification
|
Lorbrena (lorlatinib) • cyclophosphamide • topotecan • Neulasta (pegfilgrastim) • Neupogen (filgrastim)
1year
Genomic ALK alterations in primary and relapsed neuroblastoma. (PubMed, Br J Cancer)
The considerably increased frequency of ALK mutations at relapse and their high prevalence in young stage 4 patients suggest surveying the genomic ALK status regularly in these patient cohorts, and to evaluate ALK-targeted treatment also in intermediate-risk patients.
Journal
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ALK (Anaplastic lymphoma kinase)
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ALK mutation • ALK R1275Q • ALK amplification
1year
Combination Therapies Targeting Alk-Aberrant Neuroblastoma in Preclinical Models. (PubMed, Clin Cancer Res)
In our preclinical neuroblastoma models, high ALK expression was associated with lorlatinib response alone or in combination with either chemotherapy or idasanutlin. The synergy between MDM2 and ALK inhibition warrants further evaluation of this combination as a potential clinical approach for children with neuroblastoma.
Preclinical • Journal • Combination therapy
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ALK (Anaplastic lymphoma kinase)
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ALK mutation • ALK amplification
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Lorbrena (lorlatinib) • doxorubicin hydrochloride • cyclophosphamide • vincristine • idasanutlin (RG7388)
1year
ALK amplification and rearrangements are recurrent targetable events in congenital and adult glioblastoma (AACR 2023)
These findings support expanded evaluation of brain-penetrant ALK inhibitors in clinical trials across infant, pediatric, and adult GBMs.
Clinical
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ALK (Anaplastic lymphoma kinase) • DCTN1 (Dynactin Subunit 1)
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ALK rearrangement • ALK fusion • ALK amplification
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Zykadia (ceritinib)
1year
ALK amplification and rearrangements are recurrent targetable events in congenital and adult glioblastoma. (PubMed, Clin Cancer Res)
These findings support use of brain-penetrant ALK inhibitors in clinical trials across infant, pediatric, and adult GBMs.
Journal
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ALK (Anaplastic lymphoma kinase) • DCTN1 (Dynactin Subunit 1)
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ALK rearrangement • ALK fusion • ALK amplification
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Zykadia (ceritinib)
over1year
Targeting of low ALK antigen density neuroblastoma using AND logic-gate engineered CAR-T cells. (PubMed, Cytotherapy)
These data provide further proof of concept for ALK as a neuroblastoma CAR T-cell target.
Journal • CAR T-Cell Therapy
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ALK (Anaplastic lymphoma kinase) • CD276 (CD276 Molecule)
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ALK amplification
over1year
PROFILE 1013: An Investigational Drug, Crizotinib (PF-02341066), Is Being Studied In Tumors, Except Non-Small Cell Lung Cancer, That Are Positive For Anaplastic Lymphoma Kinase (ALK) (clinicaltrials.gov)
P1b, N=44, Active, not recruiting, Pfizer | Trial completion date: Dec 2022 --> Apr 2023 | Trial primary completion date: Dec 2022 --> Apr 2023
Trial completion date • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK mutation • ALK translocation • ALK amplification
|
Xalkori (crizotinib)
over1year
Detection of Resistance Mechanisms in Cerebrospinal Fluid for EGFR-mutant, ALK- and ROS1-rearranged (clinicaltrials.gov)
P=N/A, N=0, Withdrawn, University of Colorado, Denver | N=40 --> 0 | Trial completion date: Apr 2025 --> Sep 2022 | Recruiting --> Withdrawn | Trial primary completion date: Apr 2024 --> Sep 2022
Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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EGFR mutation • ALK rearrangement • ALK mutation • ROS1 rearrangement • ROS1 mutation • ALK amplification
over1year
MET and NF2 alterations confer early resistance to first-line alectinib treatment in ALK-rearranged non-small cell lung cancer (ESMO 2022)
Of these, 52 received first-line alectinib treatment (1L) and 56 received alectinib after crizotinib resistance (2L). Also, NF2-mutant patients only had a median PFS of 4 months, significantly poorer than those without (HR 11.1, 95CI 2.17-50; p<0.001). Conclusions By analyzing different mutational profiles of ALK-rearranged patients after alectinib treatment, we proposed MET and NF2 as putative mechanisms that conferred resistance to early resistance of first-line alectinib, which shone light on future tailored treatment for ALK-positive NSCLCs.
Clinical
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF2 (Neurofibromin 2)
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KRAS mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • ALK positive • MET amplification • ALK rearrangement • ALK mutation • MET mutation • ALK G1202R • NF2 mutation • ALK G1269A • ALK I1171N • ALK I1171T • ALK I1171 • ALK L1196M • ALK amplification • ALK V1180L • ALK E1129V • ALK rearrangement + PIK3CA mutation • MET D1228H
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Xalkori (crizotinib) • Alecensa (alectinib)
almost2years
A CALL FOR GERMLINE ALK TESTING IN NEUROBLASTOMA: A CASE OF ALK+ NEUROBLASTOMA IN MOTHER & BABY (ASPHO 2022)
Targeted ALK inhibitor agents, such as crizotinib, have been effective in the relapse setting and are currently being evaluated in combination with backbone multimodal therapy in the upfront setting for high-risk ALK+ neuroblastoma... While familial neuroblastoma is rare, early detection of germline ALK mutations in patients and survivors can have a major impact on family planning and cancer surveillance in offspring. Survivors with autosomal dominant ALK mutations, like our patients mother, carry a 50% chance of passing the mutation on to each child who then carries a 5060% chance of developing a neuroblastoma-spectrum tumor if inherited. Germline ALK testing should be strongly considered in survivors of ALK+ and ALK-unknown neuroblastoma.
Clinical
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ARG1 (Arginase 1)
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ALK positive • ALK mutation • ALK amplification
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Xalkori (crizotinib)
2years
Anaplastic thyroid cancer: genome-based search for new targeted therapy options. (PubMed, Endocr Connect)
While ATC carrying BRAF mutations can benefit from BRAF-inhibitors and this effect might be enhanced by a combined strategy including PIK3CA-inhibitors in some of the patients, alterations in BRAF wild-type ATC are not directly targeted by currently FDA approved options.
Journal
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ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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BRAF V600E • PIK3CA mutation • BRAF V600 • BRAF wild-type • ALK amplification
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Aliqopa (copanlisib)
2years
A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate (ADC) demonstrates potent cytotoxicity in neuroblastoma (NBL) and fusion positive rhabdomyosarcoma (FP RMS) (AACR 2022)
ADCs directed to ALK-expressing cancers are a promising therapeutic approach. The efficacy of the ADCs are currently being tested in NBL and FP RMS mouse models, and will be reported.
PARP Biomarker
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ALK (Anaplastic lymphoma kinase) • CASP3 (Caspase 3)
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ALK mutation • ALK amplification
2years
Negative ultra-selection of patients with RAS/BRAF wild-type (wt), microsatellite stable (MSS) metastatic colorectal cancer (mCRC) receiving anti-EGFR-based therapy: The PRESSING2 study (AACR 2022)
In the era of comprehensive genomic profiling, several resistance alterations with extremely low prevalence may be detected, especially in CRCs that do not bear other genomic drivers. Negative ultra-selection may represent a relevant step forward in precision medicine in patients with RAS/BRAF wt MSS mCRC potentially eligible for EGFR blockade.
Clinical
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • ARAF (A-Raf Proto-Oncogene)
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BRAF V600E • KRAS mutation • HER-2 amplification • PIK3CA mutation • BRAF V600 • HER-2 mutation • MET amplification • RET fusion • FGFR2 mutation • BRAF wild-type • FGFR2 fusion • FGFR2 amplification • ROS1 fusion • MET mutation • AKT1 mutation • ALK amplification • AKT1 amplification • EGFR fusion
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FoundationOne® CDx
2years
Acquired concurrent EGFR T790M and driver gene resistance from EGFR-TKIs hampered osimertinib efficacy in advanced lung adenocarcinoma (ELCC 2022)
One patient had acquired EGFR T790M, STRN-ALK fusion, and EGFR amplification after gefitinib progression and was shortly resistant to osimertinib with MET amplification. The other patient developed to acquired EGFR T790M and MET amplification post-dacomitinib and acquired CCDC6-RET fusion after 4-month osimertinib treatment...The T790M accompanying diver gene resistance will be a new subtype after EGFR-TKIs progression and needs effective treatment options. Legal entity responsible for the study The authors.
Clinical
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • CCDC6 (Coiled-Coil Domain Containing 6) • STRN (Striatin)
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EGFR mutation • HER-2 amplification • MET amplification • EGFR T790M • RET fusion • EGFR amplification • ALK fusion • CCDC6-RET fusion • KRAS G12 • KRAS amplification • STRN-ALK fusion • ALK amplification • EGFR T790M + HER-2 amplification • EGFR T790M + MET amplification
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Tagrisso (osimertinib) • gefitinib • Vizimpro (dacomitinib)
2years
NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922) (clinicaltrials.gov)
P1, N=40, Recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2022
Trial completion date • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase)
|
ALK fusion • ALK mutation • ALK translocation • ALK amplification
|
Lorbrena (lorlatinib) • cyclophosphamide • topotecan
2years
Detection of Resistance Mechanisms in Cerebrospinal Fluid for EGFR-mutant, ALK- and ROS1-rearranged (clinicaltrials.gov)
P=N/A, N=40, Recruiting, University of Colorado, Denver | Not yet recruiting --> Recruiting
Enrollment open
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
EGFR mutation • ALK rearrangement • ALK mutation • ROS1 rearrangement • ROS1 mutation • ALK amplification
over2years
Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives. (PubMed, Int J Mol Sci)
There is an increasing utilization of agnostic testing which involves the analysis of all potentially actionable genes across all tumor types. The invention of genomically tailored treatment has resulted in a spectacular improvement in disease outcomes for a significant portion of cancer patients.
Review • Journal • Tumor Mutational Burden
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
HER-2 amplification • MET exon 14 mutation • PIK3CA amplification • ALK translocation • ALK amplification
over2years
New trial
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
EGFR mutation • ALK rearrangement • ALK mutation • ROS1 rearrangement • ROS1 mutation • ALK amplification
over2years
Clinical • New P1/2 trial • Combination therapy
|
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK3 fusion • ROS1 fusion • ALK amplification • NTRK1 mutation
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temozolomide • irinotecan • Augtyro (repotrectinib)
almost3years
The genomic characteristics of different progression patterns in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors. (PubMed, Ann Transl Med)
Mutations in RAD54L (P=0.018) and MYC (P=0.04) were more common in FP patients; HPD patients showed more frequent RAD54L mutations (P<0.001). We demonstrated different genomic characteristics across different progression patterns following ICI treatment, which might assist clinicians in the prediction of a patient's response, identifying candidates for more effective ICI therapy.
Clinical • Journal • Checkpoint inhibition • Tumor Mutational Burden • IO biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • CDKN1B (Cyclin dependent kinase inhibitor 1B)
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KRAS mutation • EGFR mutation • HER-2 amplification • HER-2 mutation • MET amplification • RET fusion • EGFR amplification • ALK fusion • ALK mutation • MET mutation • ATRX mutation • ALK amplification • NTRK1 mutation • RAD54L mutation
almost3years
Frequency and Prognostic Impact of ALK Amplifications and Mutations in the European Neuroblastoma Study Group (SIOPEN) High-Risk Neuroblastoma Trial (HR-NBL1). (PubMed, J Clin Oncol)
Genetic alterations of ALK (clonal mutations and amplifications) in HR-NB are independent predictors of poorer survival. These data provide a rationale for integration of ALK inhibitors in upfront treatment of HR-NB with ALK alterations.
Journal
|
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
ALK mutation • MYCN amplification • ALK amplification
almost3years
Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations. (PubMed, J Pathol Transl Med)
High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.
Journal
|
ALK (Anaplastic lymphoma kinase) • TERT (Telomerase Reverse Transcriptase)
|
ALK amplification
3years
Activity of Crizotinib in Patients with ALK-aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912). (PubMed, Clin Cancer Res)
Despite limited activity seen in this trial, we conclude that this is more likely due to an inability to reach the higher concentrations of crizotinib needed to overcome the competing ATP affinity.
Clinical • Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK mutation • ALK amplification
|
Xalkori (crizotinib)
3years
NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922) (clinicaltrials.gov)
P1, N=40, Recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Dec 2020 --> Dec 2022 | Trial primary completion date: May 2020 --> Dec 2021
Clinical • Trial completion date • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase)
|
ALK fusion • ALK mutation • ALK translocation • ALK amplification
|
Lorbrena (lorlatinib) • topotecan • cyclophosphamide intravenous
over3years
FISH patterns of ROS1, MET, and ALK with a correlation of ALK immunohistochemistry in lung cancer: a case for introducing ALK immunohistochemistry 'Equivocal' interpretation category in the Ventana anti-ALK (D5F3) CDx assay - A tertiary cancer center experience. (PubMed, Indian J Cancer)
An ALK IHC "equivocal" interpretation category should be incorporated into practice. Atypical patterns of ROS1 and genomic heterogeneity need to be evaluated further for any clinical relevance.
Journal • Clinical
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
ALK positive • MET amplification • ALK rearrangement • ALK mutation • ROS1 positive • ROS1 rearrangement • MET mutation • ROS1 mutation • EGFR negative • ALK amplification
|
VENTANA ALK (D5F3) CDx Assay
over3years
Strong ALK and PD-L1 positive IHC expression related ALK amplification in an advanced lung sarcomatoid carcinoma: A therapeutic trap? (PubMed, Lung Cancer)
We demonstrated that IHC positive test, in these cases, must be interpreted with caution. FISH analysis has to be recommended to confirm IHC results in case of unusual phenotype, such as smoker or lung cancer other than adenocarcinoma. Although lung carcinoma with ALK rearrangement seems to be not sensitive to ICI, further investigations should be conducted on other types of ALK molecular alterations. ALK amplifications, as observed in the present case, should not be an impediment to taking into account the PD-L1 marking for the initiation of treatment by immunotherapy.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
|
PD-L1 expression • ALK positive • ALK rearrangement • ALK amplification
over3years
Genomic characterization of a PPP1CB-ALK fusion with fusion gene amplification in a congenital glioblastoma. (PubMed, Cancer Genet)
Copy number analyses of genes between PPP1CB and ALK using RT-qPCR suggest that the PPP1CB-ALK is likely the result of local chromothripsis followed by episomal amplification. Transcriptome sequencing demonstrated high-level SOX2 expression and predicted WNT/β-catenin pathway activation, suggesting possible therapeutic approaches.
Journal
|
ALK (Anaplastic lymphoma kinase) • SOX2
|
ALK fusion • ALK translocation • ALK amplification
over3years
[VIRTUAL] Alectinib in ALK-Rearranged NSCLC Patients Following Crizotinib. Final Results and Biological Outcomes - Phase II ATALK Study (IASLC-WCLC 2020)
Conclusion Alectinib efficacy and safety profile in this study align with known alectinib results in post-crizotinib setting. Identification of mechanisms of resistance emerging from exposure to previous ALK inhibitor was feasible and helped selecting subsequent treatment options.
Clinical • P2 data
|
ALK (Anaplastic lymphoma kinase)
|
ALK rearrangement • ALK amplification
|
Xalkori (crizotinib) • Alecensa (alectinib)
over3years
An Investigational Drug, Crizotinib (PF-02341066), Is Being Studied In Tumors, Except Non-Small Cell Lung Cancer, That Are Positive For Anaplastic Lymphoma Kinase (ALK) (clinicaltrials.gov)
P1b, N=44, Active, not recruiting, Pfizer | Trial completion date: Dec 2020 --> Dec 2022 | Trial primary completion date: Dec 2020 --> Dec 2022
Clinical • Trial completion date • Trial primary completion date
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK mutation • ALK translocation • ALK amplification
|
Xalkori (crizotinib)
over3years
Novel resistance mechanisms including L1196Q, P1094H, and R1248_D1249insertion in three patients with non-small-cell lung cancer following ALK tyrosine kinase inhibitor treatment. (PubMed, J Thorac Oncol)
The combination of a genetic analysis and computational simulation model may make a prediction of resistance mechanisms for overcoming ALK-TKI resistance, and the construction of a genomic and simulation fused database is important for the development of personalized medicine in this field.
Clinical • Journal
|
ALK (Anaplastic lymphoma kinase)
|
ALK positive • ALK G1269A • ALK I1171N • ALK I1171 • ALK L1196M • ALK amplification
over3years
Prevalence and potential biologic role of TERT amplifications in ALK-translocated adenocarcinoma of the lung. (PubMed, Histopathology)
Our preliminary study shows that ALK+-adenocarcinomas should be evaluated in the context of their genomic background in order to better understand and predict patients´ individual course of disease.
Journal
|
TP53 (Tumor protein P53) • TERT (Telomerase Reverse Transcriptase)
|
TP53 mutation • ALK translocation • ALK amplification • TERT amplification
|
FoundationOne® CDx