Poster Presentation 29th Lorne Cancer Conference 2017

Engineering models of FGFR3-TACC3-driven respiratory cancers (#166)

Cassandra Harapas 1 2 3 , Sarah Best 1 2 , Ariena Kersbergen 2 , Kate Sutherland 1 2
  1. Dept Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
  2. ACRF Stem Cells and Cancer Division, Walter + Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
  3. Cancer Therapeutics CRC, Parkville, VIC, Australia

Cancers of the respiratory system, including lung squamous cell carcinoma (SCC) and
nasopharyngeal carcinoma (NPC), are aggressive malignancies with low survival rates.
This is largely due to late detection and a lack of targeted therapeutic agents. Identifying
the molecular drivers of cancer permits for a better understanding of tumour progression
and an opportunity for the development of targeted treatment strategies.
Sequencing studies have revealed the presence of a genetic fusion between
fibroblast growth factor receptor 3 (FGFR3) and transforming acidic coiled-coil 3
(TACC3) in subset of lung SCC and NPCs. To interrogate the role of FGFR3-TACC3 in
oncogenic transformation of the respiratory epithelium we have utilised a combination in
vitro and sophisticated in vivo approaches.
We have demonstrated that expression of the FGFR3-TACC3 fusion protein
increased the proliferation potential of human lung SCC cells. Furthermore, FGFR3-
TACC3 expressing lung SCC cells were sensitive to an FGFR inhibitor compound,
revealing the efficacy of clinically available targeted therapies in the treatment of FGFR3-
TACC3-driven cancers.
Notably, conditional activation of FGFR3-TACC3 in vivo promoted hyperplastic
transformation of respiratory epithelial cells lining the nasal cavity. Combined loss of
tumour suppressor gene, p53, accelerated these effects, indicating that FGFR3-TACC3
and p53 loss co-operate in tumourgenesis. Taken together, this model provides an
effective tool to examine FGFR3-TACC3-driven malignant transformation, facilitating a
comprehensive understanding on how FGFR3-TACC3-expressing cancers can be
effectively targeted in the clinic.