ALK C1156Y

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Lung Adenocarcinoma2
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	C	Supports Resistance	4	accepted	EID236 A 28 year-old patient with T4N3M1 stage lung adenocarcinoma harboring an EML4-ALK variant 1 fusion was treated with crizotinib after failing conventional therapy. The patient achieved a partial respon… (full text at CIViC) PMID 20979473 · Choi et al., 2010 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	C	Supports Resistance	2	accepted	EID4046 In a lung adenocarcinoma cancer patient with an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation, ALK C1156Y was reported to be refractory to cr… (full text at CIViC) PMID 27045755 · Saber et al., 2016 · Open in CIViC	civic

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Lung Adenocarcinoma2

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

accepted

EID236

A 28 year-old patient with T4N3M1 stage lung adenocarcinoma harboring an EML4-ALK variant 1 fusion was treated with crizotinib after failing conventional therapy. The patient achieved a partial respon… (full text at CIViC)

PMID 20979473 · Choi et al., 2010 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

accepted

EID4046

In a lung adenocarcinoma cancer patient with an EML4-ALK gene rearrangement (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation, ALK C1156Y was reported to be refractory to cr… (full text at CIViC)

PMID 27045755 · Saber et al., 2016 · Open in CIViC

civic

Lung Non-Small Cell Carcinoma9
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	C	Supports Resistance	2	submitted	EID4042 In a non-small cell lung cancer patient with a liver metastatic tumor harboring an ALK gene rearrangement and an ALK C1156Y co-mutation, ALK C1156Y was reported to be refractory to 7-month crizotinib … (full text at CIViC) PMID 23434628 · Huang et al., 2013 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	D	Supports Resistance	4	accepted	EID1346 EML4-ALK variant 3 containing NSCLC cell line H2228 xenografts in SCID beige mice were treated with increasing doses of crizotinib up to 100 mg/kg per day by oral gavage. At approximately 40 days tumo… (full text at CIViC) PMID 24675041 · Friboulet et al., 2014 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	D	Supports Resistance	2	submitted	EID4043 In an in vitro study, H3122 cells expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation demonstrated resistance to crizotinib treatment (240 nmol/L vs… (full text at CIViC) PMID 21791641 · Sasaki et al., 2011 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	D	Supports Resistance	2	submitted	EID4044 In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation demonstrated resistance to crizotinib treatment (180 nm… (full text at CIViC) PMID 22235099 · Doebele et al., 2012 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Ceritinib + Crizotinib + LuminespibSequential	Predictive	C	Supports Resistance	3	accepted	EID841 In this case report, a patient with metastatic, ALK-rearranged NSCLC with C1156Y mutation had tumor progression under sequential treatment with first crizotinib, then ceritinib and finally AUY922. Sub… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Ensartinib	Predictive	B	Supports Sensitivity Response	3	submitted	EID8860 In this multicentre phase II study of ALK-positive NSCLC patients that progressed on crizotinib, the safety and efficacy of 225mg daily ensartinib was assessed. Objective responses were seen in 76 (52… (full text at CIViC) PMID 31628085 · Yang et al., 2020 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Lorlatinib	Predictive	C	Supports Sensitivity Response	3	accepted	EID842 Case report of a patient with metastatic ALK-rearranged NSCLC after progression under sequential crizotinib, ceritinib, HSP90 inhibitor AUY922 and chemotherapy followed by crizotinib again. Third gene… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1198F AND ALK C1156Y	Crizotinib	Predictive	C	Supports Sensitivity Response	4	accepted	EID844 Case report of a patient with metastatic ALK-rearranged NSCLC. After developing resistance to first and second line ALK inhibitors mediated by a C1156Y mutation, the patient had a partial response wit… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1198F AND ALK C1156Y	Lorlatinib	Predictive	C	Supports Resistance	4	accepted	EID843 Case report of a patient with metastatic ALK-rearranged NSCLC. After developing resistance to first and second line ALK inhibitors mediated by a C1156Y mutation, the patient had a partial response wit… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic

Lung Non-Small Cell Carcinoma9

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

submitted

EID4042

In a non-small cell lung cancer patient with a liver metastatic tumor harboring an ALK gene rearrangement and an ALK C1156Y co-mutation, ALK C1156Y was reported to be refractory to 7-month crizotinib … (full text at CIViC)

PMID 23434628 · Huang et al., 2013 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

accepted

EID1346

EML4-ALK variant 3 containing NSCLC cell line H2228 xenografts in SCID beige mice were treated with increasing doses of crizotinib up to 100 mg/kg per day by oral gavage. At approximately 40 days tumo… (full text at CIViC)

PMID 24675041 · Friboulet et al., 2014 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

submitted

EID4043

In an in vitro study, H3122 cells expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation demonstrated resistance to crizotinib treatment (240 nmol/L vs… (full text at CIViC)

PMID 21791641 · Sasaki et al., 2011 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

submitted

EID4044

In an in vitro study, a Ba/F3 cell line expressing EML4-ALK fusion (a known sensitizing alteration to crizotinib) and an ALK C1156Y co-mutation demonstrated resistance to crizotinib treatment (180 nm… (full text at CIViC)

PMID 22235099 · Doebele et al., 2012 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Ceritinib + Crizotinib + LuminespibSequential

Predictive

Supports Resistance

accepted

EID841

In this case report, a patient with metastatic, ALK-rearranged NSCLC with C1156Y mutation had tumor progression under sequential treatment with first crizotinib, then ceritinib and finally AUY922. Sub… (full text at CIViC)

PMID 26698910 · Shaw et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Ensartinib

Predictive

Supports Sensitivity Response

submitted

EID8860

In this multicentre phase II study of ALK-positive NSCLC patients that progressed on crizotinib, the safety and efficacy of 225mg daily ensartinib was assessed. Objective responses were seen in 76 (52… (full text at CIViC)

PMID 31628085 · Yang et al., 2020 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Lorlatinib

Predictive

Supports Sensitivity Response

accepted

EID842

Case report of a patient with metastatic ALK-rearranged NSCLC after progression under sequential crizotinib, ceritinib, HSP90 inhibitor AUY922 and chemotherapy followed by crizotinib again. Third gene… (full text at CIViC)

PMID 26698910 · Shaw et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1198F AND ALK C1156Y

Crizotinib

Predictive

Supports Sensitivity Response

accepted

EID844

Case report of a patient with metastatic ALK-rearranged NSCLC. After developing resistance to first and second line ALK inhibitors mediated by a C1156Y mutation, the patient had a partial response wit… (full text at CIViC)

PMID 26698910 · Shaw et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1198F AND ALK C1156Y

Lorlatinib

Predictive

Supports Resistance

accepted

EID843

PMID 26698910 · Shaw et al., 2016 · Open in CIViC

civic

Malignant Neoplasm5
EML4::ALK Fusion AND ALK C1156Y	ALK Inhibitor TAE684	Predictive	D	Supports Sensitivity Response	3	submitted	EID11078 From a mutation assay that generated crizotinib resistant mutations in EML4::ALK, the five most resistant mutations found were introduced into Ba/F3 cells and tested with the ALK inhibitor TAE684. EML… (full text at CIViC) PMID 22034911 · Zhang et al., 2011 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	D	Supports Resistance	3	submitted	EID7613 Cells expressing EML4-ALK with the resistance mutation C1156Y were resistant to the ALK inhibitor crizotinib in vitro. In cell survival assays Ba/F3 cells with C1156Y treated with crizotinib had an IC… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Predictive	D	Supports Resistance	4	submitted	EID11069 Ba/F3 cells with EML4::ALK were subjected to mutagen N-ethyl-N-nitrosourea and then incubated without IL3 in 250, 500, 720, 1000, 1440, or 2000 nm crizotinib. The ten most frequently seen mutants we… (full text at CIViC) PMID 22034911 · Zhang et al., 2011 · Open in CIViC	civic
EML4::ALK Fusion AND ALK C1156Y	Alectinib + Brigatinib + Ceritinib + LorlatinibSubstitutes	Predictive	D	Does Not Support Resistance	4	submitted	EID7609 In vitro experiments showed that cells expressing EML4-ALK with the resistance mutation C1156Y were sensitive to second and third generation ALK inhibitors. In cell survival assays Ba/F3 cells with C1… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK L1198F AND ALK C1156Y	Crizotinib	Predictive	D	Supports Sensitivity Response	4	submitted	EID7605 The EML4-ALK fusion compound resistance mutation C1156Y-L1198F was shown to re-sensitize cells to crizotinib in vitro. In cell survival assays Ba/F3 cells expressing C1156Y-L1198F mutated EML4-ALK wer… (full text at CIViC) PMID 26698910 · Shaw et al., 2016 · Open in CIViC	civic

Malignant Neoplasm5

EML4::ALK Fusion AND ALK C1156Y

ALK Inhibitor TAE684

Predictive

Supports Sensitivity Response

submitted

EID11078

From a mutation assay that generated crizotinib resistant mutations in EML4::ALK, the five most resistant mutations found were introduced into Ba/F3 cells and tested with the ALK inhibitor TAE684. EML… (full text at CIViC)

PMID 22034911 · Zhang et al., 2011 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

submitted

EID7613

Cells expressing EML4-ALK with the resistance mutation C1156Y were resistant to the ALK inhibitor crizotinib in vitro. In cell survival assays Ba/F3 cells with C1156Y treated with crizotinib had an IC… (full text at CIViC)

PMID 26698910 · Shaw et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Crizotinib

Predictive

Supports Resistance

submitted

EID11069

Ba/F3 cells with EML4::ALK were subjected to mutagen N-ethyl-N-nitrosourea and then incubated without IL3 in 250, 500, 720, 1000, 1440, or 2000 nm crizotinib. The ten most frequently seen mutants we… (full text at CIViC)

PMID 22034911 · Zhang et al., 2011 · Open in CIViC

civic

EML4::ALK Fusion AND ALK C1156Y

Alectinib + Brigatinib + Ceritinib + LorlatinibSubstitutes

Predictive

Does Not Support Resistance

submitted

EID7609

In vitro experiments showed that cells expressing EML4-ALK with the resistance mutation C1156Y were sensitive to second and third generation ALK inhibitors. In cell survival assays Ba/F3 cells with C1… (full text at CIViC)

PMID 26698910 · Shaw et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK L1198F AND ALK C1156Y

Crizotinib

Predictive

Supports Sensitivity Response

submitted

EID7605

The EML4-ALK fusion compound resistance mutation C1156Y-L1198F was shown to re-sensitize cells to crizotinib in vitro. In cell survival assays Ba/F3 cells expressing C1156Y-L1198F mutated EML4-ALK wer… (full text at CIViC)

PMID 26698910 · Shaw et al., 2016 · Open in CIViC

civic

Evidence by cancer (16 items)

Clinical significance (0)