Navigation Links
Double-pronged attack could treat common children's cancer
Date:11/1/2013

A dual-pronged strategy using two experimental cancer drugs together could successfully treat a childhood cancer by inhibiting tumour growth and blocking off the escape routes it uses to become resistant to treatment, finds a new study.

Scientists at The Institute of Cancer Research, London, found that combining two separate molecularly targeted therapies could stop processes driving growth in a cancer called rhabdomyosarcoma, a major cause of cancer death in children.

The drugs, called AZD8055 and AZD6244, block two different signalling pathways involved in cancer growth acting like road-blocks on two separate routes that cancers could otherwise use to evade treatment.

The study, published in Clinical Cancer Research today (Friday, 1 November), was funded by the NIHR Biomedical Research Centre for Cancer at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (ICR), with additional funding from Cancer Research UK, The Royal Marsden Hospital Charitable Fund and the Chris Lucas Trust.

Rhabdomyosarcoma tumours can form anywhere in the body and resemble primitive muscle tissue. Despite advances in treatment options, there has been little improvement in outcome for patients with rhabdomyosarcoma in decades and they remain difficult to treat.

Previous research has shown that many rhabdomyosarcomas display activity of the PI3 Kinase signalling pathway, which plays a key role in cancer growth. However, blocking this pathway in other cancer types can lead to alternative signalling pathways becoming active to compensate, allowing resistance to treatment to develop.

In this study, scientists at the ICR targeted the PI3 Kinase pathway and a second pathway called MAP Kinase, to assess any compensatory signalling and determine if blocking both pathways could effectively inhibit rhabdomyosarcoma cell growth.

The researchers found that the PI3 Kinase pathway was active in 83% of rhabdomyosarcoma samples from patients, and that 43% of these also showed activation of the MAP Kinase pathway. In experiments on rhabdomyosarcoma cells to block either pathway alone, they saw compensatory signalling through the alternative pathway, suggesting that inhibiting both pathways is an essential approach to treatment, irrespective of whether MAP kinase signalling was initially activated.

The researchers tested rhabdomyosarcomas with drugs known to be effective against the PI3 Kinase and MAP Kinase pathways. When they tried the drugs AZD8055 and AZD6244 separately they saw reduced cell growth and a decrease in levels of markers showing the activity of the signalling pathways. However, compensatory activity was clearly evident.

But when they combined the two drugs they found a synergistic effect, with cell growth reduced to a greater extent than with either treatment alone. They saw similar synergistic results when AZD8055 and AZD6244 were used together in mice with rhabdomyosarcoma tumours, with tumour marker levels reduced to less than 30% of those in controls.

Co-author Dr Janet Shipley, Team Leader in Sarcoma Molecular Pathology at The Institute of Cancer Research, said:

"Rhabdomyosarcoma is the main type of sarcoma to affect children and little improvement has been made recently using conventional treatments like chemotherapy and radiotherapy - survival rates for some patients with this disease remain bleak. More effective targeted treatment is desperately needed. Our study shows that treating with one or other of these two drugs is not a good strategy but that combining them is a very promising option."

Co-author Dr Jane Renshaw, Senior Scientific Officer at The Institute of Cancer Research, said:

"We found that while most rhabdomyosarcoma tumours seem to have active PI3K signalling, inhibiting this pathway alone isn't enough to be an effective treatment. Cross-talk between the PI3 Kinase and MAP Kinase pathways means that cancer is able to find an alternative route, like traffic finding a way around a road-block. Targeting both pathways using two drugs together stops that compensatory action.

"These two drugs are being tested for use against cancers in adults so the next step will be to progress with clinical trials for children using the dual approach."

Nell Barrie, Cancer Research UK's Senior Science Communication Manager, said:

"Understanding the inner workings of cancer cells is crucial to finding the best ways to tackle the disease. This lab research emphasises the importance of targeting each cancer's weak points and combining drugs to develop more effective treatments which are urgently needed to improve survival for children's cancers like rhabdomyosarcoma. Further research and clinical trials will shed light on whether this promising drug combination could help save more lives."


'/>"/>

Contact: Lauren King
lauren.king@icr.ac.uk
020-715-35380
Institute of Cancer Research
Source:Eurekalert

Related medicine news :

1. Heart Attack Season Survival Tips
2. New Paper Argues Attacks on Family Planning Funds Limit Affordable Care Act's Effectiveness
3. Practical Self-Defense Teaching Manual, “One Strong Move,” Uses Cartoon-Illustrations To Engage Teens And Adults In Learning How To Spot Danger And Stop An Attack
4. Study shows no increased risk for heart attacks among HIV-positive patients with high CD4 cell count
5. Panic Away Review Reveals Natural Ways to Stop Panic Attacks
6. Flu shot halves risk of heart attack or stroke in people with history of heart attack, study finds
7. Flu shot halves risk of heart attack or stroke in people with history of heart attack, study finds
8. Heart Attack Reinforces Farmers’ Market Manager’s Mission and Alliance with HMHP
9. Asthma attack prevention proposal awarded NIH New Innovator grant
10. Medicare expenses for patients with heart attacks increase between 1998 and 2008
11. Brown & Toland Physicians Honors Heart Attack Survivor Jeffrey Houck with Lifestyle Change Award During Heart Walk
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... 2016 , ... "With 30 hand-drawn hand gesture animations, FCPX users can easily ... of Pixel Film Studios. , ProHand Cartoon’s package transforms over 1,300 hand-drawn pictures ... . Simply select a ProHand generator and drag it above media or text in ...
(Date:6/25/2016)... ... 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe earned his ... David Geffen School of Medicine at UCLA. He trained in Internal Medicine at Scripps ... in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the opportunity to ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, Van ... Wellness at Work award to iHire in recognition of their exemplary accomplishments in worksite ... 7th annual Maryland Workplace Health & Wellness Symposium at the BWI Marriott in Linthicum ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article ... are unfamiliar with. The article goes on to state that individuals are now more ... these less common operations such as calf and cheek reduction. The Los Angeles area ...
(Date:6/24/2016)... ... 2016 , ... June 19, 2016 is World Sickle Cell Observance Day. In ... benefits of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued ... Sickle Cell Disease (SCD) is a disorder of the red blood cells, which can ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 2016  Consumers have taken a more active ... more emphasis on patient outcomes. ... the pharmaceutical industry have evolved beyond just providing ... are focusing on becoming more patient-oriented across their ... services that improve health. ...
(Date:6/24/2016)... June 24, 2016   Bay Area Lyme ... Dean Center for Tick Borne Illness , ... Rehabilitation, MIT Hacking Medicine, University of California, Berkeley, ... announced the five finalists of Lyme Innovation ... More than 100 scientists, clinicians, researchers, entrepreneurs, and ...
(Date:6/24/2016)... The Academy of Managed Care Pharmacy (AMCP) ... would allow biopharmaceutical companies to more easily share health ... and coverage decisions, a move that addresses the growing ... The recommendations address restrictions in the sharing of ... label, a prohibition that hinders decision makers from accessing ...
Breaking Medicine Technology: