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Page 10 of 17 Li et al. J Cancer Metastasis Treat 2020;6:14 I http://dx.doi.org/10.20517/2394-4722.2020.27

Table 1. FGFR fusions and fusion partners in solid tumors
Cancer Type 5’-gene 3’-gene
Bladder FGFR1 NTM
FGFR3 TACC3, TNIP2, JAKMIP1, BAIAP2L1
Breast FGFR1 ADAM18
RHOT1 FGFR1
NSD3 FGFR1
ERLIN2 FGFR1
FGFR2 CCDC6, AFF3, CASP7, NCALD, WHSC1
Cervical cancer FGFR3 TACC3
Cholangiocarcinoma FGFR2 AFF4, AHCYL1, BICC1, CCDC6, VCL, CLIP1, POC1B, CELF2, CREB5,
DNAJC12, HOOK1, KCTD1, KIAA1217, KIAA1598, MGEA5, NOL4,
OPTN, PARK2, PCMI, PPHLN1, RASAL2, SLMAP2, SORBS1, STK26,
STK3, TACC3, TBC1D1, TFEC, TRA2B, UBQLN1, WAC, ZMYM4
Colorectal cancer FGFR2 NPM1, COL14A1
Gastric cancer FGFR2 C100rf68, PDHX, TACC2
Glioblastoma FGFR3 TACC3
Head and neck squamous cell carcinoma FGFR3 TACC3, TPRG1
Lung squamous cell carcinoma BAG4 FGFR1
FGFR2 CCAR2, CIT, KIAA1967
CCAR2 FGFR2
FGFR3 TACC3
Mesothelioma FGFR2 CASC15
Ovarian cancer FGFR2 USP10
Prostate adenocarcinoma FGFR2 KLK2, PPAPDC1A, SLC45A3
FGFR3 AES
Renal cell carcinoma FGFR3 TACC3
Thyroid cancer FGFR2 OFD1
VCL FGFR2

FGFR: Fibroblast growth factor receptor

occur so that the FGFR gene remains intact on the 3’ end of the gene (Type I fusions) allowing the fusion
[95]
partner to be present on the 5’ end [88,94] ; these fusions are mostly found in hematological malignancies .
Given the significance of constitutive FGFR signaling in tumorigenesis and progression, small molecule
inhibitors targeting this pathway have been developed and their anti-tumor activities are currently being
evaluated in clinical trials [88,96,97] . For instance, recent results from several clinical trials in FGFR2-fusion-
positive cholangiocarcinoma have demonstrated meaningful clinical efficacy, which supports potential
approvals as second line therapy for the treatment of advanced cholangiocarcinoma with FGFR2 fusions.
For example, in a Phase II study of infigratinib in 71 cholangiocarcinoma patients with FGFR2 fusions,
[98]
ORR 31% and SD 58% were observed, with median PFS and OS of 6.8 and 12.5 months, respectively .
Similar results were reported based on an interim update from the Phase II study of pemigatinib in FGFR2-
[99]
fusion-positive cholangiocarcinoma patients . Erdatinib, recently approved for advanced or metastatic
urothelial carcinoma with susceptible FGFR3 mutations, has demonstrated efficacy in therapeutic trials
for cholangiocarcinoma patients with FGFR2 fusions, although these trials contained fewer patients [100] .
Additionally, a covalent pan-FGFR inhibitor, futibatinib, has shown limited efficacy in cholangiocarcinoma
patients previously treated with a different FGFR inhibitor, suggesting a potential utility for later line
therapy when drug sequencing is needed .
[101]
In addition to cholangiocarcinoma, there is evidence, albeit very limited, that FGFR inhibitors work
in other solid tumors with FGFR1, -2, or -3 fusions [97,102-104] . Based on these data there is a rationale for
performing tumor-agnostic clinical trials in molecularly defined cancers to maximally benefit patients with
serious and life-threatening diseases.

RET
RET encodes a single-pass transmembrane receptor tyrosine kinase important for normal cellular
proliferation, development, and maintenance. It has four cadherin-like repeats at the N-terminal