Dr Louis Chesler

The goal of our laboratory is to improve the treatment and survival of children with neuroblastoma, medulloblastoma and rhabdomyosarcoma, three paediatric solid tumours in which high-risk patient cohorts can be defined by alterations in a single oncogene. We focus on the role of the MYCN oncogene, since aberrant expression of MYCN is very significantly associated with high-risk in all three diseases and implies that they may have a common cell-of-origin.

Elucidating the molecular signalling pathways that control expression of the MYCN oncoprotein and targeting these pathways with novel therapeutics is a major goal of the laboratory. We use a variety of innovative preclinical drug development platforms for this purpose. Technologically, we focus on genetically engineered cancer models incorporating novel imaging (optical and fluorescent) modalities that can be used as markers to monitor disease progression and therapeutic response.

Dr Louis Chesler is working to develop new drugs for poor-outcome children’s cancers that at present respond poorly to existing treatment.  These cancers include the three most common solid tumours of children: neuroblastoma, a nerve tumour, rhabdomyosarcoma, a muscle tumour and medulloblastoma, a brain tumour. He leads the Paediatric Solid Tumour Biology and Therapeutics within The Institute of Cancer Research’s Clinical Studies Division.

South African-born Dr Chesler completed his early scientific and medical training in the United States, taking his Bachelor of Science (Honours) at the University of Wisconsin-Madison and his MD and PhD at Northwestern University and Medical School in Chicago. During this time he also worked for the US government’s National Institute of Health and National Cancer Institute as an Intramural Fellow. In 1995, he joined the University of California, San Francisco, working as a paediatric oncology consultant and running a neuroblastoma research programme, before moving to the ICR in 2007 as a Senior Clinical Lecturer.

Dr Chesler was attracted to paediatric cancer research because it allows him to make a long-lasting contribution to children’s lives. “We have patients who go on to graduate high school, attend university and get married - seeing them have their own children is amazing, the most rewarding of all,” he says.

Relapses are common with paediatric cancers, Dr Chesler says, and the high-dose therapies required for treatment in this situation can have serious side-effects including long term disability, organ dysfunction and even second cancers. Dr Chesler and his team are developing drugs specifically targeted at children’s cancers, as most drugs currently given to children were originally designed for adults. “The ICR is known for its excellent work in the development of novel targeted therapeutics for adult cancer, and we need to apply this expertise to children’s cancer,” Dr Chesler says.

Part of Dr Chesler’s work includes investigating the MYCN gene, which is necessary for normal development of the brain and nervous system but causes cancers in these tissues if it is erroneously expressed. He is developing new drugs to target MYCN, which he hopes will have fewer side-effects than existing treatments. Dr Chesler hopes that a drug developed in his own laboratory will one day lead to clinical trials that will improve survival in paediatric cancer. “Our current work is on the right track to achieving that goal,” he says.

“Ideally I would like to develop a one-a-day pill that would be free of side-effects and would be very effective against a children’s cancer. This sounds unrealistic but has already been achieved for an adult cancer. The drug Gleevec [ imatinib ] is a one-a-day pill for adults that is effective and comes without the side-effects associated with previous treatments – we need a Gleevec for children,” he says.

Dr Chesler believes that the ICR’s close links with industry and The Royal Marsden NHS Foundation Trust has created a new model of efficiency for drug development. “This partnership is unique and allows me to devote most of my time to laboratory research while retaining significant clinical involvement on the paediatric oncology ward,” he says.

Dr Chesler is a member of the American Association for Cancer Research and the American Association of Paediatrics and is on the editorial board for several peer-reviewed journals.

Away from work, Dr Chesler enjoys visiting historic buildings and cultural sites in the UK, cycling and the outdoors.