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Journal of Medical Oncology & Therapeutics | Volume 4
Oncology & Cancer Therapy
International Conference on
March 18-19, 2019 | London, UK
L
ung and bladder cancers are mostly incurable due to
early development of drug resistance and metastatic
dissemination. Hence, novel therapies that tackle these two
processes are urgently needed to improve clinical outcome.
We have identified RSK4 as a promoter of drug resistance
and metastasis in lung and bladder cancer cells and silencing
this kinase sensitises to therapy and hinders metastasis
in vitro and in vivo. This is mediated through inhibition of
the NFkB pathway and the transcription of anti-apoptotic
proteins such as BCL2, cIAP1 and cIAP2. Drug screening
revealed several floxacin antibiotics as potent RSK4
activation inhibitors and trovafloxacin reproduces all effects
of RSK4 silencing in vitro and in vivo. Through crystallography
and Markov transient analysis, we propose a mechanism for
the action of this compound. Finally, we show that patients
undergoing chemotherapy and adhering to prophylactic
levofloxacin in the large placebo-controlled randomised
phase3 SIGNIFICANT Trial had significantly increased long-
term overall survival times. Hence, we suggest that RSK4
inhibition represents a novel therapeutic strategy for treating
lung and bladder cancer.
Speaker Biography
Olivier E Pardo graduated from the Faculty of Pharmacy Paris-V, France where he was
awarded a Doctorate in Industrial Pharmacy (1997). He completed his PhD at Imperial
College-London (2002), UK and subsequently joined the laboratory of Prof. Julian
Downward at the CRUK-LRI as a post-doctoral fellow. In 2006, he became team leader
at Imperial College-London, Department of Surgery and Cancer where he created the
Cellular Regulatory Networks lab. His team focuses on understanding the molecular
mechanisms underlying chemo-resistance and metastasis in lung and other cancers.
This involves multidisciplinary collaborations with other labs in the UK, France, the
US, Canada and China bringing in biochemistry, molecular biology, physics and bio-
informatics expertise. The data generated by his lab led to the initiation of several
clinical trials in lung and breast cancer patients.
e:
o.pardo@imperial.ac.ukOlivier E Pardo
Imperial College, UK
Targeting RSK4 prevents both chemoresistance and metastasis in lung and bladder
cancer: Potential of re-purposed floxacins as novel therapeutic agents