FGFR Fusions in Cancer: From Diagnostic Approaches to Therapeutic Intervention

被引:86
作者
De Luca, Antonella [1 ]
Esposito Abate, Riziero [1 ]
Rachiglio, Anna Maria [1 ]
Maiello, Monica Rosaria [1 ]
Esposito, Claudia [1 ]
Schettino, Clorinda [2 ]
Izzo, Francesco [3 ]
Nasti, Guglielmo [4 ]
Normanno, Nicola [1 ]
机构
[1] Ist Nazl Tumori IRCCS Fdn G Pascale, Cell Biol & Biotherapy Unit, I-80131 Naples, Italy
[2] Ist Nazl Tumori IRCCS Fdn G Pascale, Clin Trials Unit, I-80131 Naples, Italy
[3] Ist Nazl Tumori IRCCS Fdn G Pascale, Hepatobiliary Unit, Div Surg Oncol, I-80131 Naples, Italy
[4] Ist Nazl Tumori IRCCS Fdn G Pascale, SSD Innovat Therapies Abdominal Canc, I-80131 Naples, Italy
关键词
fibroblast growth factor receptors; FGFR fusions; next generation sequencing; cancer; FGFR inhibitors; GROWTH-FACTOR RECEPTOR; UNIQUE MOLECULAR SUBTYPE; GENE FUSIONS; UROTHELIAL CARCINOMA; TARGETED THERAPY; OPEN-LABEL; PHASE-II; IDENTIFICATION; MUTATIONS; CHOLANGIOCARCINOMA;
D O I
10.3390/ijms21186856
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors involved in many biological processes. Deregulated FGFR signaling plays an important role in tumor development and progression in different cancer types.FGFRgenomic alterations, includingFGFRgene fusions that originate by chromosomal rearrangements, represent a promising therapeutic target. Next-generation-sequencing (NGS) approaches have significantly improved the discovery ofFGFRgene fusions and their detection in clinical samples. A variety of FGFR inhibitors have been developed, and several studies are trying to evaluate the efficacy of these agents in molecularly selected patients carryingFGFRgenomic alterations. In this review, we describe the most frequentFGFRaberrations in human cancer. We also discuss the different approaches employed for the detection ofFGFRfusions and the potential role of these genomic alterations as prognostic/predictive biomarkers.
引用
收藏
页码:1 / 18
页数:18
相关论文
共 71 条
  • [1] Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study
    Abou-Alfa, Ghassan K.
    Sahai, Vaibhav
    Hollebecque, Antoine
    Vaccaro, Gina
    Melisi, Davide
    Al-Rajabi, Raed
    Paulson, Andrew S.
    Borad, Mitesh J.
    Gallinson, David
    Murphy, Adrian G.
    Oh, Do-Youn
    Dotan, Efrat
    Catenacci, Daniel, V
    Van Cutsem, Eric
    Ji, Tao
    Lihou, Christine F.
    Zhen, Huiling
    Feliz, Luis
    Vogel, Arndt
    [J]. LANCET ONCOLOGY, 2020, 21 (05) : 671 - 684
  • [2] AACR Project GENIE: Powering Precision Medicine through an International Consortium
    Andre, Fabrice
    Arnedos, Monica
    Baras, Alexander S.
    Baselga, Jose
    Bedard, Philippe L.
    Berger, Michael F.
    Bierkens, Mariska
    Calvo, Fabien
    Cerami, Ethan
    Chakravarty, Debyani
    Dang, Kristen K.
    Davidson, Nancy E.
    Del Vecchio, Fitz Catherine
    Dogan, Semih
    DuBois, Raymond N.
    Ducar, Matthew D.
    Futreal, P. Andrew
    Gao Jianjiong
    Garcia, Francisco
    Gardos, Stu
    Gocke, Christopher D.
    Gross, Benjamin E.
    Guinney, Justin
    Heins, Zachary J.
    Hintzen, Stephanie
    Horlings, Hugo
    Hudecek, Jan
    Hyman, David M.
    Kamel-Reid, Suzanne
    Kandoth, Cyriac
    Kinyua, Walter
    Kumari, Priti
    Kundra, Ritika
    Ladanyi, Marc
    Lefebvre, Celine
    LeNoue-Newton, Michele L.
    Lepisto, Eva M.
    Levy, Mia A.
    Lindeman, Neal, I
    Lindsay, James
    Liu, David
    Lu Zhibin
    MacConaill, Laura E.
    Ian, Maurer
    Maxwell, David S.
    Meijer, Gerrit A.
    Meric-Bernstam, Funda
    Micheel, Christine M.
    Miller, Clinton
    Mills, Gordon
    [J]. CANCER DISCOVERY, 2017, 7 (08) : 818 - 831
  • [3] Fibroblast Growth Factor Receptor 2 Tyrosine Kinase Fusions Define a Unique Molecular Subtype of Cholangiocarcinoma
    Arai, Yasuhito
    Totoki, Yasushi
    Hosoda, Fumie
    Shirota, Tomoki
    Hama, Natsuko
    Nakamura, Hiromi
    Ojima, Hidenori
    Furuta, Koh
    Shimada, Kazuaki
    Okusaka, Takuji
    Kosuge, Tomoo
    Shibata, Tatsuhiro
    [J]. HEPATOLOGY, 2014, 59 (04) : 1427 - 1434
  • [4] Advances and challenges in targeting FGFR signalling in cancer
    Babina, Irina S.
    Turner, Nicholas C.
    [J]. NATURE REVIEWS CANCER, 2017, 17 (05) : 318 - 332
  • [5] The FGF family: biology, pathophysiology and therapy
    Beenken, Andrew
    Mohammadi, Moosa
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2009, 8 (03) : 235 - 253
  • [6] Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma
    Borad, Mitesh J.
    Champion, Mia D.
    Egan, Jan B.
    Liang, Winnie S.
    Fonseca, Rafael
    Bryce, Alan H.
    McCullough, Ann E.
    Barrett, Michael T.
    Hunt, Katherine
    Patel, Maitray D.
    Young, Scott W.
    Collins, Joseph M.
    Silva, Alvin C.
    Condjella, Rachel M.
    Block, Matthew
    McWilliams, Robert R.
    Lazaridis, Konstantinos N.
    Klee, Eric W.
    Bible, Keith C.
    Harris, Pamela
    Oliver, Gavin R.
    Bhavsar, Jaysheel D.
    Nair, Asha A.
    Middha, Sumit
    Asmann, Yan
    Kocher, Jean-Pierre
    Schahl, Kimberly
    Kipp, Benjamin R.
    Fritcher, Emily G. Barr
    Baker, Angela
    Aldrich, Jessica
    Kurdoglu, Ahmet
    Izatt, Tyler
    Christoforides, Alexis
    Cherni, Irene
    Nasser, Sara
    Reiman, Rebecca
    Phillips, Lori
    McDonald, Jackie
    Adkins, Jonathan
    Mastrian, Stephen D.
    Placek, Pamela
    Watanabe, Aprill T.
    LoBello, Janine
    Han, Haiyong
    Von Hoff, Daniel
    Craig, David W.
    Stewart, A. Keith
    Carpten, John D.
    [J]. PLOS GENETICS, 2014, 10 (02):
  • [7] FGFR3-TACC3: A novel gene fusion in cervical cancer
    Carneiro, Benedito A.
    Elvin, Julia A.
    Kamath, Suneel D.
    Ali, Siraj M.
    Paintal, Ajit S.
    Restrepoe, Alvaro
    Berry, Emily
    Giles, Francis J.
    Johnson, Melissa L.
    [J]. GYNECOLOGIC ONCOLOGY REPORTS, 2015, 13 : 53 - 56
  • [8] Phase II Study of AZD4547 in Patients With Tumors Harboring Aberrations in the FGFR Pathway: Results From the NCI-MATCH Trial (EAY131) Subprotocol W
    Chae, Young K.
    Hong, Fangxin
    Vaklavas, Christos
    Cheng, Heather H.
    Hammerman, Peter
    Mitchell, Edith P.
    Zwiebel, James A.
    Ivy, S. Percy
    Gray, Robert J.
    Li, Shuli
    McShane, Lisa M.
    Rubinstein, Larry V.
    Patton, David
    Williams, P. Mickey
    Hamilton, Stanley R.
    Mansfield, Aaron
    Conley, Barbara A.
    Arteaga, Carlos L.
    Harris, Lyndsay N.
    O'Dwyer, Peter J.
    Chen, Alice P.
    Flaherty, Keith T.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (21) : 2407 - +
  • [9] Fluorescence in situ hybridization in surgical pathology: principles and applications
    Cheng, Liang
    Zhang, Shaobo
    Wang, Lisha
    MacLennan, Gregory T.
    Davidson, Darrell D.
    [J]. JOURNAL OF PATHOLOGY CLINICAL RESEARCH, 2017, 3 (02) : 73 - 99
  • [10] Mutation Profiling in Cholangiocarcinoma: Prognostic and Therapeutic Implications
    Churi, Chaitanya R.
    Shroff, Rachna
    Wang, Ying
    Rashid, Asif
    Kang, HyunSeon C.
    Weatherly, Jacqueline
    Zuo, Mingxin
    Zinner, Ralph
    Hong, David
    Meric-Bernstam, Funda
    Janku, Filip
    Crane, Christopher H.
    Mishra, Lopa
    Vauthey, Jean-Nicholas
    Wolff, Robert A.
    Mills, Gordon
    Javle, Milind
    [J]. PLOS ONE, 2014, 9 (12):