Navigation Links
Scientists develop new strategy to overcome drug-resistant childhood cancer
Date:7/11/2012

A new drug combination could offer hope to children with neuroblastoma one of the deadliest forms of childhood cancer by boosting the effectiveness of a promising new gene-targeted treatment.

Researchers at The Institute of Cancer Research in London have found a way to overcome the resistance of cancer cells to a drug called crizotinib, which recently showed positive early results in its first trial in children with cancer.

Crizotinib has already been licensed by the US Food and Drug Administration for use in adult cancers, but early experience suggests tumours eventually stop responding to treatment, after developing additional mutations in the ALK gene targeted by the drug.

The paper, led by The Institute of Cancer Research in collaboration with the Dana-Farber Cancer Institute and Children's Hospital in Boston, publishes this week in the prestigious journal Cancer Cell. The study received funding from a variety of sources including The Neuroblastoma Society, Cancer Research UK, Sparks, the children's medical research charity and The Rooney Foundation.

In the study, scientists detailed their new strategy of combining crizotinib with a second class of drugs mTOR inhibitors to knock out the resistance of cancer cells.

Scientists identified the strategy after revealing for the first time the role played by the ALK cancer-causing gene in driving neuroblastoma, which accounts for 15 per cent of all the UK's childhood cancer deaths.

Neuroblastomas are cancers of the developing nervous system, and new drug combinations are desperately needed as aggressive forms of the disease are very difficult to treat with conventional chemotherapy.

Senior author Dr Louis Chesler, leader of the neuroblastoma drug development team at The Institute of Cancer Research and honorary consultant at The Royal Marsden NHS Foundation Trust, said: "With the first paediatric clinical trial reporting substantial responses to crizotinib in patients with ALK driven tumours, we are looking for ways to increase the effectiveness of ALK inhibitors in general. We have identified a very promising way to overcome crizotinib resistance in neuroblastoma, by adding a second drug called an mTOR inhibitor. Many mTOR inhibitors are already in adult clinical trials."

"We hope that our work will benefit children with neuroblastoma by increasing the effectiveness of crizotinib. Our study may also have relevance for adult patients with ALK-driven lung cancer and lymphoma who develop resistance to crizotinib, because loss of treatment response in these patients correlates with the development of point mutations in the tyrosine kinase domain of ALK. In children with neuroblastoma these point mutations are in fact the most common primary somatic changes that we see in ALK, so we hope our work with a paediatric cancer will in this case help to unravel resistance mechanisms in adult cancer as well."

Neuroblastoma patients with ALK mutations frequently have alterations to the MYCN gene, which is closely linked to the development of aggressive neuroblastoma but is difficult to target directly with drugs.

The team therefore set out to investigate how a common ALK mutation, ALKF1174L, and alterations in MYCN interact to drive the onset of neuroblastomas, and also to attempt to find a way to overcome resistance to crizotinib.

They found that the ALKF1174L mutation and changes in MYCN cause more aggressive, crizotinib-resistant neuroblastoma, by turning on the PI3K/AKT/mTOR pathway. This pathway has been implicated in the development of neuroblastoma and many adult cancer types, and has been an intense focus of drug-development in adult cancer.

The team found that combining an mTOR inhibitor with crizotinib prevented the growth of neuroblastoma by simultaneously inhibiting MYCN and ALK, overcoming the resistance of these tumours to treatment with crizotinib alone. As well as delivering a strategy to overcome crizotinib resistance in general, this work highlights a treatment approach that may be effective for patients with aggressive neuroblastoma who carry both genetic changes at diagnosis.


'/>"/>
Contact: ICR Science Communications Manager Jane Bunce
jane.bunce@icr.ac.uk
44-020-715-35106
Institute of Cancer Research
Source:Eurekalert

Related medicine news :

1. Scientists solving the mystery of human consciousness
2. Scientists uncover multiple faces of deadly breast cancer
3. Scientists identify major source of cells defense against oxidative stress
4. Scientists tailor cell surface targeting system to hit organelle ZIP codes
5. Scientists rewrite rulebook on breast cancer in landmark global study
6. Warwick scientists uncover how checkpoint proteins bind chromosomes
7. NIH scientists link quickly spreading gene to Asian MRSA epidemic
8. Joslin scientists identify important mechanism that affects the aging process
9. Scripps Research scientists show how memory B cells stay in class to fight different infections
10. Scientists Map Melanomas Genome
11. A*STAR scientists discover switch to boost anti-viral response to fight infectious diseases
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... (PRWEB) , ... June 26, 2016 , ... Brent Kasmer, a legally blind and certified ... be personalized through a fitness app. The fitness app plans to fix the two major ... only offer a one size fits all type program , They don’t eliminate ...
(Date:6/25/2016)... ... ... "With 30 hand-drawn hand gesture animations, FCPX users can easily customize each ... Film Studios. , ProHand Cartoon’s package transforms over 1,300 hand-drawn pictures into hand ... select a ProHand generator and drag it above media or text in the Final ...
(Date:6/25/2016)... Canada (PRWEB) , ... June 25, 2016 , ... Conventional ... pursuit of success. In terms of the latter, setting the bar too high can ... risk more than just slow progress toward their goal. , Research from ...
(Date:6/24/2016)... Dallas, Texas (PRWEB) , ... June 24, 2016 ... ... 12th International Conference and Scientific Sessions in Dallas that it will receive two ... Announcement of the grants came as PHA marked its 25th anniversary by recognizing ...
(Date:6/24/2016)... Plano, TX (PRWEB) , ... June 24, 2016 , ... ... taking part in Genome magazine’s Code Talker Award, an essay contest in which patients ... for an award to be presented at the 2016 National Society of Genetic Counselors ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... 2016  MedSource announced today that it has ... solution of choice.  This latest decision demonstrates MedSource,s ... their clients by offering a state-of-the-art electronic data ... nowEDC as the EDC platform of choice in ... "nowEDC has long been a preferred EDC platform ...
(Date:6/23/2016)... INDIANAPOLIS , June 23, 2016 Roche ... received 510(k) clearance for its Elecsys BRAHMS PCT (procalcitonin) ... severe sepsis or septic shock. With this clearance, Roche ... provide a fully integrated solution for sepsis risk assessment ... associated with bacterial infection and PCT levels in blood ...
(Date:6/23/2016)... , June 23, 2016 , ... on Thursday, July 7, 2016 , , , , LOCATION: ... , , , , EXPERT PANELISTS:  , , , ... Senior Industry Analyst, Christi Bird; Senior Industry Analyst, Divyaa Ravishankar and ... The global pharmaceutical industry is witnessing an exceptional era. ...
Breaking Medicine Technology: