Background
TRK fusions are rare but drive oncogenesis in diverse tissue lineages
Tumor type | NTRK1/2/3 involved (frequency) | Detection methods |
---|---|---|
Ph-like acute lymphoblastic leukemia | NTRK3 (1/154) | RNA-seq, whole-genome seq, whole-exome seq [18] |
Appendiceal adenocarcinoma | NTRK (unspecified) (2/97) | MALDI-TOF mass spectroscopy genotyping (Sequenom), targeted NGS (MSK-IMPACT) [19] |
Astrocytoma | NTRK2 (3/96) | RNA-seq, whole-genome seq [20] |
Breast invasive carcinoma | NTRK3 (1/1072) | RNA-seq (TCGA) [21] |
Intrahepatic cholangiocarcinoma | NTRK1 (1/28) | Targeted NGS [22] |
Colon adenocarcinoma | NTRK1 (8/1559) | IHC, RT-PCR [23] |
NTRK1 (1/66) | IHC, RT-PCR [24] | |
NTRK3 (2/286) | RNA-seq (TCGA) [21] | |
GIST | NTRK3 (1/186) | Targeted NGS (Foundation Medicine) [25] |
NTRK3 (1/31) | RNA-seq, FISH, RT-PCR [26] | |
Glioblastoma | NTRK1 (1/157) | RNA-seq (TCGA) [21] |
NTRK1 (2/185) | RNA-seq (TCGA and other) [27] | |
NTRK1 (3/115) | Targeted NGS [28] | |
Brain low-grade glioma | NTRK2 (2/461) | RNA-seq (TCGA) [21] |
Pediatric DIPG and non-brainstem high-grade glioma | NTRK1 (3/127) | RNA-seq, whole-genome seq [29] |
NTRK2 (3/127) | RNA-seq, whole-genome seq [29] | |
NTRK3 (2/127) | RNA-seq, whole-genome seq [29] | |
Head and neck squamous cell carcinoma | NTRK2 (1/411) | RNA-seq (TCGA) [21] |
NTRK3 (1/411) | RNA-seq (TCGA) [21] | |
Congenital mesoblastic nephroma | NTRK3 (5/6) | RT-PCR, FISH [30] |
NTRK3 (10/15) | RT-PCR [31] | |
NTRK3 (13/19) | FISH [32] | |
Infantile (congenital) fibrosarcoma | NTRK3 (10/11) | RT-PCR, IHC [33] |
NTRK3 (5/5) | RT-PCR, FISH [30] | |
Lung adenocarcinoma | NTRK1 (3/91) | Targeted NGS (Foundation Medicine), FISH [34] |
NTRK2 (1/513) | RNA-seq (TCGA) [21] | |
Breast secretory carcinoma | NTRK3 (12/13) | RT-PCR, FISH [35] |
NTRK3 (9/9) | FISH, targeted NGS [36] | |
Mammary analogue secretory carcinoma (MASC) of salivary glands | NTRK3 (13/14) | RT-PCR, FISH [37] |
NTRK3 (15/15) | FISH [38] | |
NTRK3 (5/6) | FISH, targeted NGS [36] | |
NTRK3 (16/20) | RT-PCR, FISH [39] | |
Melanoma (skin cutaneous) | NTRK3 (1/374) | RNA-seq (TCGA) [21] |
Spitz tumors and spitzoid melanoma | NTRK1(23/140) | Targeted NGS(Foundation Medicine), FISH, IHC [40] |
Sarcoma (NOS) | NTRK1 (1/103) | RNA-seq (TCGA) [21] |
Uterine sarcoma | NTRK1 (3/97) | RNA-seq, FISH, IHC, targeted NGS [41] |
NTRK3 (1/97) | RNA-seq, FISH, IHC, targeted NGS [41] | |
Thyroid carcinoma | NTRK1 (5/498) | RNA-seq (TCGA) [21] |
NTRK3 (7/498) | RNA-seq (TCGA) [21] | |
Papillary thyroid carcinoma | NTRK1 (15/119) | RT-PCR [42] |
NTRK1 (2/38) | Southern [43] | |
NTRK1(pediatric) (1/27) | Targeted NGS [44] | |
NTRK3(radiation-associated) (2/26) | RNA-seq [45] | |
NTRK3(radiation-associated) (9/62) | RNA-seq [46] | |
NTRK3(sporadic) (3/151) | RNA-seq [46] | |
NTRK3(pediatric) (6/27) | Targeted NGS [44] |
TRK inhibitor larotrectinib demonstrates efficacy in a basket trial
Drug name | Targets | Development stage | Clinical trial identifier | Company |
---|---|---|---|---|
LOXO-101 (larotrectinib) | NTRK1/2/3 | Phase II | NCT02122913 NCT02637687 NCT02576431 NCT03213704 | Loxo Oncology |
LOXO-195 | NTRK1/2/3 (resistant) | Phase I/II | NCT03215511 | Loxo Oncology |
RXDX-101 (entrectinib) | NTRK1/2/3, ALK, ROS1 | Phase I/II, Phase II, Phase I/Ib | NCT02097810 NCT02568267 NCT02650401 | Ignyta |
TPX-0005 (ropotrectinib) | NTRK1/2/3, ALK, ROS1 (resistant), JAK2, SRC, DDR1, FAK | Phase I/II | NCT03093116 | TP Therapeutics |
LY2801653 (merestinib) | NTRK1/2/3, MET, MST1R, FLT3, AXL, MERTK, TEK, ROS1, DDR1/2, MKNK1/2 | Phase II | NCT02920996 | Eli Lilly and Company |
DS-6051b | NTRK1/2/3, ROS1 | Phase I | NCT02675491 NCT02279433 | Daiichi Sankyo |
PLX7486 | NTRK1/2/3, CSF1R | Phase I | NCT01804530 | Plexxikon/Daiichi Sankyo |
MGCD516 (sitravatinib) | NTRK1/2/3, MET, KIT, PDGFRA, KDR, DDR2, RET, CBL | Phase I/Ib | NCT02219711 | Mirati Therapeutics |