198:
29:
592:"Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement Summary of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update"
286:. However, crizotinib showed no improvement on overall survival compared to chemotherapy. This may be due to the fact that there was a 70% crossover rate to crizotinib in patients treated initially with chemotherapy. Also, patients who tested negative for EML4/ALK fusion had a response rate to crizotinib of up to 35%.
241:
is a second generation targeted therapy (FDA approved in 2014), manufactured by
Novartis and sold under the brand name Zykadia that also targets the EML4 fusion gene. When compared to Crizotinib, early studies showed Ceritinib and other second generation ALK inhibitors demonstrated superior central
331:
Iyevleva, Aglaya G.; Raskin, Grigory A.; Tiurin, Vladislav I.; Sokolenko, Anna P.; Mitiushkina, Natalia V.; Aleksakhina, Svetlana N.; Gariullina, Aigul R.; Strelkova, Tatiana N.; Merkulov, Valery O.; Ivantsov, Alexandr O.; Kuligina, Ekatherina Sh.; Pozharisski, Kazimir M.; Togo, Alexandr V.;
1060:
Solomon, Benjamin J.; Mok, Tony; Kim, Dong-Wan; Wu, Yi-Long; Nakagawa, Kazuhiko; Mekhail, Tarek; Felip, Enriqueta; Cappuzzo, Federico; Paolini, Jolanda; Usari, Tiziana; Iyer, Shrividya; Reisman, Arlene; Wilner, Keith D.; Tursi, Jennifer; Blackhall, Fiona; PROFILE 1014 Investigators (2014).
747:
Chow, Laura Q. M.; Barlesi, Fabrice; Bertino, Erin M.; van den Bent, Martin J.; Wakelee, Heather A.; Wen, Patrick Y.; Chiu, Chao-Hua; Orlov, Sergey; Chiari, Rita; Majem, Margarita; McKeage, Mark; Yu, Chong-Jen; Garrido, Pilar; Hurtado, Felipe K.; Arratia, Pilar
Cazorla (2022-06-13).
300:
gene fusions occur almost exclusively in carcinomas arising in non-smokers. About 4% of non-small-cell lung carcinomas involve an EML4-ALK tyrosine kinase fusion gene. 4–6% of lung adenocarcinomas involve the fusion gene.
637:
Hendriks, L. E.; Kerr, K. M.; Menis, J.; Mok, T. S.; Nestle, U.; Passaro, A.; Peters, S.; Planchard, D.; Smit, E. F.; Solomon, B. J.; Veronesi, G.; Reck, M.; ESMO Guidelines
Committee. Electronic address:
273:
Although treatment with immune checkpoint inhibitors has proved effective with some types of non-small cell lung cancer, it seems to be generally ineffective with ALK positive non-small cell lung cancer.
509:"Clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase-positive advanced pulmonary adenocarcinoma: suggestion for an effective screening strategy for these tumors"
289:
According to patient advocacy group ALK Positive, a study in
December 2018 found that the median survival for people with stage 4 (IV) ALK-positive lung cancer was 6.8 years with the right care.
819:
1112:
235:
is a targeted therapy (FDA approved in 2011), manufactured by Pfizer and marketed under the brand name
Xalkori and Crizalk that targets the EML4/ALK fusion gene.
867:"Will the clinical development of 4th-generation "double mutant active" ALK TKIs (TPX-0131 and NVL-655) change the future treatment paradigm of ALK+ NSCLC?"
750:"ASCEND-7: Efficacy and Safety of Ceritinib Treatment in Patients with ALK-Positive Non-Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges"
698:
Kazandjian, Dickran; Blumenthal, Gideon M.; Chen, Huan-Yu; He, Kun; Patel, Mona; Justice, Robert; Keegan, Patricia; Pazdur, Richard (2014-08-28).
371:
Soda M, Choi YL, Enomoto M, et al. (August 2007). "Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer".
795:
1245:
213:
700:"FDA Approval Summary: Crizotinib for the Treatment of Metastatic Non-Small Cell Lung Cancer With Anaplastic Lymphoma Kinase Rearrangements"
221:
258:
a second generation targeted therapy (FDA approved in 2017), manufactured by Takeda and is marketed under the brand name
Alunbrig.
643:"Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up"
197:
840:
242:
nervous system (CNS) penetration leading to superior anti-tumor response in patients with metastatic disease to the CNS.
485:
183:
172:
93:
28:
796:"Japan becomes first country to approve Roche's alectinib for people with a specific form of advanced lung cancer"
565:
925:
105:. Less frequently, there will be novel translocation partners for the ALK gene, in place of EML4. This abnormal
283:
179:
1047:
948:
947:
Jahanzeb, Mohammad; Lin, Huamao M; Pan, Xiaoyun; Yin, Yu; Baumann, Pia; Langer, Corey J (17 September 2020).
216:
as well as the
European Society of Medical Oncology. Screening in the United States of most often done with
949:"Immunotherapy Treatment Patterns and Outcomes Among ALK-Positive Patients With Non-Small-Cell Lung Cancer"
333:
1106:
270:
NVL-655 is a fourth generation targeted therapy (currently in clinical trials), developed by
Nuvalent.
865:
Ou, Sai-Hong
Ignatius; Nagasaka, Misako; Brazel, Danielle; Hou, Yujie; Zhu, Viola W. (November 2021).
1282:
380:
217:
799:
1001:"Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs"
978:
538:
404:
212:
Screening for ALK positive lung cancer is now a standard of care and strongly recommended by the
261:
Ensartinib is a second generation targeted therapy (trial drug X-396), manufactured by XCovery.
1140:"Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Who Harbor EML4-ALK"
248:
another second generation targeted therapy and was approved (for this) in Japan in 2014 and by
1241:
1218:
1169:
1125:
1094:
1030:
970:
898:
777:
769:
719:
680:
672:
619:
611:
530:
453:
396:
353:
48:
1208:
1200:
1159:
1151:
1084:
1074:
1020:
1012:
960:
888:
878:
761:
727:
711:
662:
654:
603:
520:
443:
435:
388:
345:
384:
1213:
1188:
1164:
1139:
1025:
1000:
893:
866:
732:
699:
448:
423:
267:
is a third generation targeted therapy (FDA approved in 2018), manufactured by Pfizer.
70:
1276:
982:
715:
542:
186:
variants are more likely to carry this fused gene than other histological variants.
408:
113:
that appears, in many cases, to promote and maintain the malignant behavior of the
765:
40:
1189:"EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues"
883:
658:
525:
508:
349:
124:
fusion gene was first reported in non-small cell lung carcinoma (NSCLC) in 2007.
639:
252:
in 2015., manufactured by
Genentech and marketed under the brand name Alecensa.
205:
106:
66:
1204:
965:
439:
1016:
832:
264:
255:
232:
201:
36:
1155:
773:
723:
676:
615:
749:
642:
591:
245:
238:
189:
The median age at diagnosis is around 50 years and the majority are female.
63:
1222:
1173:
1098:
1062:
1034:
974:
902:
781:
684:
623:
534:
457:
400:
357:
1264:
1079:
477:
607:
667:
392:
1089:
1063:"First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer"
590:
Kalemkerian, Gregory P.; Narula, Navneet; Kennedy, Erin B. (May 2018).
557:
110:
917:
249:
139:
Chest pain that gets worse with deep breathing, coughing, or laughing
114:
424:"The biology and treatment of EML4-ALK non-small cell lung cancer"
196:
1138:
Shaw AT, Yeap BY, Mino-Kenudson M, et al. (September 2009).
1187:
Martelli MP, Sozzi G, Hernandez L, et al. (February 2009).
102:
88:
83:
74:
820:
New Oral Therapy To Treat ALK-Positive Lung Cancer. Dec 2015
204:
showing an ALK positive adenocarcinoma of the lung. ALK
171:
Most lung carcinomas containing the ALK gene fusion are
422:
Sasaki T, Rodig SJ, Chirieac LR, Jänne PA (July 2010).
1265:
EML4 echinoderm microtubule associated protein like 4
73:contain a characteristic abnormal configuration of
47:
21:
1236:Kumar, V; Abbas AK; Aster JC (2013). "Chapter 5".
1240:(9th ed.). Elsevier Saunders. p. 212.
79:echinoderm microtubule-associated protein-like 4
507:Koh Y, Kim DW, Kim TM, et al. (May 2011).
145:Weight loss without trying or loss of appetite
132:The signs and symptoms of this cancer include
710:(10). Oxford University Press (OUP): e5–e11.
8:
1111:: CS1 maint: numeric names: authors list (
307:mutation rarely occurs in combination with
994:
992:
334:"Novel ALK fusion partners in lung cancer"
39:showing ALK positive lung adenocarcinoma.
27:
18:
1212:
1163:
1088:
1078:
1024:
964:
892:
882:
731:
666:
524:
447:
1126:Summary of safety and effectiveness data
323:
282:Treatment with crizotinib achieves 60%
1104:
1048:Highlights of prescribing information
916:Nuvalent Pipeline (5 February 2023).
860:
858:
332:Imyanitov, Evgeny N. (28 June 2015).
214:American Society of Clinical Oncology
7:
1005:Cellular and Molecular Life Sciences
928:from the original on 8 December 2022
843:from the original on 3 December 2022
585:
583:
568:from the original on 17 January 2023
471:
469:
467:
556:ALK Positive UK (5 February 2023).
488:from the original on 7 October 2020
478:"What is ALK-Positive lung cancer?"
999:Bayliss, R; Choi, J (March 2016).
14:
476:ALK Positive (5 February 2023).
1067:New England Journal of Medicine
716:10.1634/theoncologist.2014-0241
184:signet ring cell adenocarcinoma
178:Some studies suggest that the
77:wherein, most frequently, the
1:
766:10.1158/1078-0432.CCR-21-1838
109:leads to the production of a
1144:Journal of Clinical Oncology
884:10.1016/j.tranon.2021.101191
659:10.1016/j.annonc.2022.12.009
596:Journal of Oncology Practice
526:10.1097/JTO.0b013e3182111461
350:10.1016/j.canlet.2015.03.028
136:A cough that doesn't go away
831:Xcovery (5 February 2023).
360:– via Science Direct.
1299:
1205:10.2353/ajpath.2009.080755
966:10.1016/j.cllc.2020.08.003
440:10.1016/j.ejca.2010.04.002
94:anaplastic lymphoma kinase
1017:10.1007/s00018-015-2117-6
35:
26:
1156:10.1200/JCO.2009.22.6993
754:Clinical Cancer Research
180:papillary adenocarcinoma
60:ALK positive lung cancer
22:ALK positive lung cancer
1238:Robbins Basic Pathology
154:A weak or tired feeling
871:Translational Oncology
209:
1080:10.1056/NEJMoa1408440
200:
953:Clinical Lung Cancer
608:10.1200/JOP.18.00035
218:immunohistochemistry
918:"Nuvalent Pipeline"
393:10.1038/nature05945
385:2007Natur.448..561S
151:Shortness of breath
647:Annals of Oncology
220:(IHC) staining or
210:
128:Signs and symptoms
1247:978-1-4377-1781-5
1150:(26): 4247–4253.
1073:(23): 2167–2177.
760:(12): 2506–2516.
148:Coughing up blood
120:The transforming
57:
56:
16:Medical condition
1290:
1252:
1251:
1233:
1227:
1226:
1216:
1184:
1178:
1177:
1167:
1135:
1129:
1123:
1117:
1116:
1110:
1102:
1092:
1082:
1057:
1051:
1045:
1039:
1038:
1028:
1011:(6): 1209–1224.
996:
987:
986:
968:
944:
938:
937:
935:
933:
913:
907:
906:
896:
886:
862:
853:
852:
850:
848:
828:
822:
817:
811:
810:
808:
807:
798:. Archived from
792:
786:
785:
744:
738:
737:
735:
695:
689:
688:
670:
634:
628:
627:
587:
578:
577:
575:
573:
553:
547:
546:
528:
504:
498:
497:
495:
493:
473:
462:
461:
451:
419:
413:
412:
368:
362:
361:
328:
91:is fused to the
31:
19:
1298:
1297:
1293:
1292:
1291:
1289:
1288:
1287:
1273:
1272:
1260:
1255:
1248:
1235:
1234:
1230:
1186:
1185:
1181:
1137:
1136:
1132:
1124:
1120:
1103:
1059:
1058:
1054:
1046:
1042:
998:
997:
990:
946:
945:
941:
931:
929:
915:
914:
910:
864:
863:
856:
846:
844:
830:
829:
825:
818:
814:
805:
803:
794:
793:
789:
746:
745:
741:
697:
696:
692:
636:
635:
631:
589:
588:
581:
571:
569:
562:ALK Positive UK
555:
554:
550:
506:
505:
501:
491:
489:
475:
474:
465:
434:(10): 1773–80.
421:
420:
416:
379:(7153): 561–6.
370:
369:
365:
330:
329:
325:
321:
295:
280:
230:
195:
173:adenocarcinomas
169:
164:
130:
17:
12:
11:
5:
1296:
1294:
1286:
1285:
1275:
1274:
1271:
1270:
1259:
1258:External links
1256:
1254:
1253:
1246:
1228:
1179:
1130:
1118:
1052:
1040:
988:
939:
908:
854:
823:
812:
787:
739:
704:The Oncologist
690:
653:(4): 339–357.
641:(April 2023).
629:
602:(5): 323–327.
579:
548:
513:J Thorac Oncol
499:
463:
428:Eur. J. Cancer
414:
363:
344:(1): 116–121.
338:Cancer Letters
322:
320:
317:
294:
291:
279:
276:
229:
226:
194:
191:
168:
167:Classification
165:
163:
160:
159:
158:
155:
152:
149:
146:
143:
140:
137:
129:
126:
55:
54:
51:
45:
44:
33:
32:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
1295:
1284:
1281:
1280:
1278:
1269:
1268:
1262:
1261:
1257:
1249:
1243:
1239:
1232:
1229:
1224:
1220:
1215:
1210:
1206:
1202:
1199:(2): 661–70.
1198:
1194:
1193:Am. J. Pathol
1190:
1183:
1180:
1175:
1171:
1166:
1161:
1157:
1153:
1149:
1145:
1141:
1134:
1131:
1127:
1122:
1119:
1114:
1108:
1100:
1096:
1091:
1086:
1081:
1076:
1072:
1068:
1064:
1056:
1053:
1049:
1044:
1041:
1036:
1032:
1027:
1022:
1018:
1014:
1010:
1006:
1002:
995:
993:
989:
984:
980:
976:
972:
967:
962:
958:
954:
950:
943:
940:
927:
923:
919:
912:
909:
904:
900:
895:
890:
885:
880:
876:
872:
868:
861:
859:
855:
842:
838:
834:
827:
824:
821:
816:
813:
802:on 2018-02-15
801:
797:
791:
788:
783:
779:
775:
771:
767:
763:
759:
755:
751:
743:
740:
734:
729:
725:
721:
717:
713:
709:
705:
701:
694:
691:
686:
682:
678:
674:
669:
664:
660:
656:
652:
648:
644:
640:
633:
630:
625:
621:
617:
613:
609:
605:
601:
597:
593:
586:
584:
580:
567:
563:
559:
552:
549:
544:
540:
536:
532:
527:
522:
519:(5): 905–12.
518:
514:
510:
503:
500:
487:
483:
479:
472:
470:
468:
464:
459:
455:
450:
445:
441:
437:
433:
429:
425:
418:
415:
410:
406:
402:
398:
394:
390:
386:
382:
378:
374:
367:
364:
359:
355:
351:
347:
343:
339:
335:
327:
324:
318:
316:
314:
310:
306:
302:
299:
292:
290:
287:
285:
284:response rate
277:
275:
271:
268:
266:
262:
259:
257:
253:
251:
247:
243:
240:
236:
234:
227:
225:
223:
219:
215:
207:
203:
199:
192:
190:
187:
185:
181:
176:
174:
166:
161:
156:
153:
150:
147:
144:
141:
138:
135:
134:
133:
127:
125:
123:
118:
116:
112:
108:
104:
100:
96:
95:
90:
86:
85:
80:
76:
72:
68:
65:
62:is a primary
61:
52:
50:
46:
42:
41:H&E stain
38:
34:
30:
25:
20:
1267:Homo sapiens
1266:
1263:Entrez Gene
1237:
1231:
1196:
1192:
1182:
1147:
1143:
1133:
1121:
1107:cite journal
1070:
1066:
1055:
1043:
1008:
1004:
959:(1): 49–57.
956:
952:
942:
930:. Retrieved
921:
911:
874:
870:
845:. Retrieved
836:
833:"Ensartinib"
826:
815:
804:. Retrieved
800:the original
790:
757:
753:
742:
707:
703:
693:
668:1887/3750398
650:
646:
632:
599:
595:
570:. Retrieved
561:
551:
516:
512:
502:
490:. Retrieved
482:ALK Positive
481:
431:
427:
417:
376:
372:
366:
341:
337:
326:
312:
308:
304:
303:
297:
296:
293:Epidemiology
288:
281:
272:
269:
263:
260:
254:
244:
237:
231:
211:
188:
177:
170:
131:
121:
119:
98:
92:
82:
78:
59:
58:
1283:Lung cancer
1090:2434/426878
877:(11): 1–9.
315:mutations.
206:immunostain
107:gene fusion
932:5 February
847:5 February
806:2016-02-11
572:5 February
492:5 February
319:References
265:Lorlatinib
256:Brigatinib
233:Crizotinib
202:Micrograph
142:Hoarseness
67:lung tumor
37:Micrograph
983:224908622
774:1557-3265
724:1083-7159
677:1569-8041
616:1935-469X
278:Prognosis
246:Alectinib
239:Ceritinib
228:Treatment
193:Screening
162:Diagnosis
64:malignant
49:Specialty
1277:Category
1223:19147828
1174:19667264
1099:25470694
1035:26755435
975:33250347
926:Archived
922:Nuvalent
903:34365220
841:Archived
782:35091443
685:36872130
624:29589987
566:Archived
543:38377715
535:21358343
486:Archived
458:20418096
401:17625570
358:25813404
305:EML4-ALK
298:EML4-ALK
182:and the
157:Wheezing
122:EML4-ALK
53:Oncology
1214:2630573
1165:2744268
1026:4761370
894:8353359
837:Xcovery
733:4201002
558:"Facts"
449:2888755
409:2172543
381:Bibcode
117:cells.
111:protein
1244:
1221:
1211:
1172:
1162:
1097:
1033:
1023:
981:
973:
901:
891:
780:
772:
730:
722:
683:
675:
622:
614:
541:
533:
456:
446:
407:
399:
373:Nature
356:
250:US FDA
115:cancer
69:whose
979:S2CID
539:S2CID
405:S2CID
309:K-RAS
71:cells
1242:ISBN
1219:PMID
1170:PMID
1113:link
1095:PMID
1031:PMID
971:PMID
934:2023
899:PMID
849:2023
778:PMID
770:ISSN
720:ISSN
681:PMID
673:ISSN
620:PMID
612:ISSN
574:2023
531:PMID
494:2023
454:PMID
397:PMID
354:PMID
313:EGFR
222:FISH
103:gene
89:gene
84:EML4
1209:PMC
1201:doi
1197:174
1160:PMC
1152:doi
1128:FDA
1085:hdl
1075:doi
1071:371
1050:FDA
1021:PMC
1013:doi
961:doi
889:PMC
879:doi
762:doi
728:PMC
712:doi
663:hdl
655:doi
604:doi
521:doi
444:PMC
436:doi
389:doi
377:448
346:doi
342:362
311:or
99:ALK
75:DNA
1279::
1217:.
1207:.
1195:.
1191:.
1168:.
1158:.
1148:27
1146:.
1142:.
1109:}}
1105:{{
1093:.
1083:.
1069:.
1065:.
1029:.
1019:.
1009:73
1007:.
1003:.
991:^
977:.
969:.
957:22
955:.
951:.
924:.
920:.
897:.
887:.
875:14
873:.
869:.
857:^
839:.
835:.
776:.
768:.
758:28
756:.
752:.
726:.
718:.
708:19
706:.
702:.
679:.
671:.
661:.
651:34
649:.
645:.
618:.
610:.
600:14
598:.
594:.
582:^
564:.
560:.
537:.
529:.
515:.
511:.
484:.
480:.
466:^
452:.
442:.
432:46
430:.
426:.
403:.
395:.
387:.
375:.
352:.
340:.
336:.
224:.
175:.
101:)
87:)
1250:.
1225:.
1203::
1176:.
1154::
1115:)
1101:.
1087::
1077::
1037:.
1015::
985:.
963::
936:.
905:.
881::
851:.
809:.
784:.
764::
736:.
714::
687:.
665::
657::
626:.
606::
576:.
545:.
523::
517:6
496:.
460:.
438::
411:.
391::
383::
348::
208:.
97:(
81:(
43:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
