Navigation Links
Study shows blood markers can help choose best dose for antiangiogenic drugs
Date:10/25/2007

Scientists at Sunnybrook have new information that may help to improve the use of anti-cancer drugs designed to block the growth of new blood vessels in tumors, a process called angiogenesis that is critical to tumor growth. While these antiangiogenic drugs are effective, at present there are no reliable methods for determining whether they are working, if the right dose is used, or if a patient will benefit (or not) from treatment.

A team led by Dr. Robert Kerbel - a senior scientist in Molecular and Cellular Biology at Sunnybrook and Canada Research Chair - has just published a paper in the October issue of the Proceedings of the National Academy of Sciences which may help to answer these questions. In the clinic, patients receiving these antiangiogenic drugs have a number of blood plasma proteins that rise and fall after treatment, so it is speculated that they could be used as surrogate biomarkers to tell us about drug activity and efficacy - our studies in mice show that this is correct, says Dr. Kerbel. In the study, Kerbels team found that drug-induced molecular changes observed in mice occurred at the same doses that had the best anti-tumor effect, suggesting that monitoring these changes in patients could predict the optimal dose of drug.

Surprisingly, the team also uncovered some unexpected insight into the nature of these observations. The current hypothesis to explain these drug-induced molecular changes is that they are tumor dependent, possibly because blocking blood flow would starve tumors of oxygen, which in turn would cause tumors to produce more proteins to recruit new vessels, says John Ebos, a doctoral student in Medical Biophysics at the University of Toronto and lead author of the study. However, our study shows that the same molecular changes occur in normal mice, that have no tumors, and come from multiple organs - suggesting that these changes come mainly from the body not the disease.

The study also found that, in addition to the molecular changes observed in the clinic, there were many other proteins that were also elevated after treatment. Ironically, many of these have been shown to have angiogenesis promoting properties and Kerbels team is now investigating the possible implications of these findings. The fact that these molecular changes occur independent of the tumor and involve many proteins that are unrelated to the drug activity, could explain why they have not been useful so far as predictors of patient benefit. They could also contribute to some of the observed drug associated toxicities seen with these drugs, play a role in drug resistance, and even may explain some recent observations where tumors rapidly regrow in some patients when therapy is stopped, using antiangiogenic drugs says Dr. Kerbel, who is also a professor in the Departments of Medical Biophysics and Laboratory Medicine/Pathobiology at University of Toronto. We are testing these hypotheses now.

In the study, the research team used a class of drugs designed to block the activation of receptors (known as receptor tyrosine kinase inhibitors, or RTKIs) activated by an important regulator of angiogenesis called vascular endothelial growth factor (VEGF). The drug they used is called sunitinib which is used for the treatment of kidney cancer, and is now being evaluated for its effects on many other types of cancer. Dr. Kerbels results have led to collaborations between his team and several medical oncologists leading clinical trials at Sunnybrooks Odette Cancer Centre involving late stage kidney cancer and early stage breast cancer therapy with the aim to determine if these preclinical findings are observed in patients, and if so, how the results might be exploited in the future to improve the benefits of antiangiogenic drugs for cancer treatment. This is a major goal of the Toronto Angiogenesis Research Centre established at Sunnybrook with the support of an infrastructure grant from the Canadian Foundation for Innovation (CFI).


'/>"/>

Contact: Natalie Chung-Sayers
natalie.chung-sayers@sunnybrook.ca
416-480-4040
Sunnybrook Health Sciences Centre
Source:Eurekalert

Related medicine news :

1. Rural Canadians travel far for specialists: study
2. A new study surpasses Gene Therapy Hurdle
3. Tomato Sauce reduces Cancer Risk- Study
4. A question on study of Adult Stem Cell
5. Study on obesity and heart failure
6. National Lung Study in the process
7. Marijuana gateway theory strengthened by study of twins
8. Old theory of adaptation confirmed by new study
9. Study casts doubt on keyboard ills
10. Gene study links endometriosis, infertility
11. Study reveals how stress can make you sick
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/1/2017)... ... March 01, 2017 , ... The Industrial Designers Society of America (IDSA) ... awareness of the profession of industrial design (ID) and relaunching "What Is ID?" ... school students and counselors; parents; and the greater public. , Share details and photos ...
(Date:3/1/2017)... Philadelphia, Pennsylvania (PRWEB) , ... March 01, 2017 , ... ... the Bucci Law Firm, filed a civil sex abuse lawsuit in the Circuit Court ... adult males, who have only been identified by their initials. See L.B. and T.B. ...
(Date:3/1/2017)... ... March 01, 2017 , ... Expert on international living and leading a healthy ... Go. , Time & Go app is the ultimate strategic compass that helps users ... management methods enable people to work smarter, not harder, that's why Time & Go ...
(Date:3/1/2017)... ... March 01, 2017 , ... ... special pricing in the month of March for treatments aimed at tightening skin ... features use on Thermage skin tightening, with 30 percent off all Thermage face ...
(Date:3/1/2017)... ... March 01, 2017 , ... “Marriage...God's Way: Key To One ... Key To One Flesh” is the creation of published author Cecilia Chiam, a writer ... Publishing, Cecilia Chiam‘s new book presents solutions to many marital problems with the guidance ...
Breaking Medicine News(10 mins):
(Date:2/28/2017)... 2017 Summary This report provides ... and its partnering interests and activities since 2010. ... The Partnering Deals and Alliance since 2010 report provides ... of the world,s leading life sciences companies. ... ensure inclusion of the most up to date deal ...
(Date:2/28/2017)... 2017 The presence of ... vendor landscape of the  Global Lap on Chips ... high degree of consolidation with the top 8 ... market in 2016. Among these enterprises Danaher Corporation, ... Laboratories enjoy dominance on account of extensive geographical ...
(Date:2/28/2017)... ... Research and Markets has announced the addition of the "Ovarian ... offering. The latest research Ovarian Cancer Drugs Price Analysis ... global Ovarian Cancer market. The research answers the following questions: ... Ovarian Cancer and their clinical attributes? How are they positioned in the ...
Breaking Medicine Technology: