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Journal of Medical Oncology & Therapeutics | Volume 4

Oncology & Cancer Therapy

International Conference on

March 18-19, 2019 | London, UK

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.

Olivier 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