Navigation Links
Emerging cancer drugs may drive bone tumors
Date:2/13/2013

Cancer drugs should kill tumors, not encourage their spread. But new evidence suggests that an otherwise promising class of drugs may actually increase the risk of tumors spreading to bone, according to researchers at Washington University School of Medicine in St. Louis.

The drugs, IAP antagonists, block survival signals that many cancer cells rely on to stay alive. Working in mice, the investigators found that targeting the same protein that makes tumors vulnerable to death also overactivates cells called osteoclasts, which are responsible for tearing down bone.

"These investigational drugs are getting broad attention right now because they seem to be very effective against primary tumors," says senior author Deborah V. Novack, MD, PhD, associate professor of medicine. "There is also excitement because until now, these drugs have not appeared to have major side effects."

The research appears in the February issue of Cancer Discovery.

In light of the study, Novack urges oncologists to think about protecting bone in patients taking IAP antagonists, including patients with cancers that don't typically spread to bone. Numerous IAP antagonists are in early clinical trials against breast, lung, pancreatic, ovarian, prostate, liver, skin and blood cancers.

"For many of these cancers, doctors are not watching bone," Novack says. "Osteoporosis is not the biggest concern when treating cancer, but if they're not doing bone scans, they may miss a cancer spreading to bone."

To maintain healthy bone, osteoclasts work in tandem with cells that build new bone. But IAP antagonists overactivate osteoclasts, destroying bone that is not replaced. In mice, the researchers showed that the drug led to osteoporosis, creating an environment that encouraged tumor growth in degrading bone, even while simultaneously killing breast cancer cells elsewhere.

After showing that the problem with IAP antagonists is specific to bone, Novack and her colleagues tested long-established drugs called bisphosphonates that inhibit osteoclasts and are used to treat osteoporosis.

"We found that bisphosphonate treatment protected bone from the negative effects of these drugs," Novack says. "While bisphosphonates are common for breast cancer patients, they're not, for example, commonly given to lung cancer patients. But since IAP antagonists are now in lung cancer trials, we're saying doctors may want to consider bisphosphonate treatment for lung cancer or other cancer patients receiving these drugs. Or at least closely monitor the bone status."

IAP antagonists are now only available to patients enrolled in phase 1 or 2 clinical trials. While these kinds of trials examine the short-term safety and effectiveness of new drugs, the researchers say they may not catch bone metastasis.

"These trials do not necessarily look for long-term effects of the drugs," says Chang Yang, MD, PhD, staff scientist and the paper's first author. "If the cancer is going to metastasize to bone, it may take six months to two years to see that outcome. This may not be seen during the clinical trial."

Numerous drug companies are developing IAP antagonists intended for many kinds of cancer, but only Genentech agreed to provide Novack and her colleagues with its drug, called BV6, to evaluate in the study. Because the investigators could not obtain other proprietary IAP antagonists, they also made two other similar drug compounds and found them to have the same detrimental effects on the bone.

And to further ensure that over-stimulated osteoclasts are the only culprit in the bone metastasis associated with these new drugs, they performed studies in mice that lack the ability to dial up the production of osteoclasts. Even when given IAP antagonists, these mice were protected from osteoporosis and osteoclast activation.

Together, Novack says the studies have demonstrated that these results are unlikely to be a quirk of a particular compound.

"The osteoporosis and spread of tumors we see in bone are unintended side effects of IAP antagonists, but they're not off-target effects," she says. "They're based on the mechanism of action for the entire class of drugs."


'/>"/>
Contact: Julia Evangelou Strait
straitj@wustl.edu
314-286-0141
Washington University School of Medicine
Source:Eurekalert  

Related medicine news :

1. NIH scientists reflect on gains in emerging infectious disease awareness, research and response
2. Chicago Hat Designer Tonya Gross Selected by Online Retailer Zappos.com for 2013 Emerging Designer Program
3. Queens scientist is named Emerging Scientist 2012
4. CWRUs Maxwell J. Mehlmans book examines issues emerging in genetic engineering
5. Expanding database enables discoveries in emerging field of metabolomics
6. New Immune-Deficiency Illness Emerging in East Asia
7. CDC Warns of Another Emerging Tick-Borne Threat
8. New Treatments Emerging from Immune and Inflammatory Disease R&D Pipelines
9. Lung cancer set to overtake breast cancer as the main cause of cancer deaths among European women
10. Watch and Wait Approach Often Best for Older Patients With Kidney Cancer
11. Research from the 2013 Genitourinary Cancers Symposium highlights new insights on high-risk prostate cancer prevalence and treatment, compares benefit of surveillance and surgery for management of small kidney tumors
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Emerging cancer drugs may drive bone tumors
(Date:2/12/2016)... FL (PRWEB) , ... February 12, 2016 , ... ... as a Service (WaaS), today announced the integration of Clarity Intelligence Platform (CIP) ... channel partners to offer real-time business intelligence (BI) to their small and medium ...
(Date:2/12/2016)... ... February 12, 2016 , ... The Jones Agency, a family owned ... Texas, is launching a cooperative charity drive with the Tarrant Area Food Bank in ... 50,000 individuals and families in need, the Tarrant County Food Bank offers hope and ...
(Date:2/12/2016)... San Ramon, CA (PRWEB) , ... February 12, 2016 , ... ... tissue donation in northern California and Nevada, announced a partnership with San Ramon Regional ... be transferred to the hospital’s facilities as a way to accommodate a more certain ...
(Date:2/12/2016)... ... February 12, 2016 , ... Mediaplanet today announces the launch ... component of “Revolutionizing Cancer Care” is distributed within the February 12 issue of ... a circulation of approximately 250,000 copies and an estimated readership of 750,000 readers. ...
(Date:2/12/2016)... ... ... US Sport Camps is pleased to announce the addition of junior golf ... the host site and directing the camps is PGA Professional and 2008 Iowa State ... recent years around Des Moines and are fortunate to have such a well-respected instructor ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... , Feb. 11, 2016 The primary goal ... future adoption patterns on the usage of liquid biopsy. ... following: - Timeframe of liquid biopsy adoption ... cfDNA and Evs—by organization type - Sample inflow to ... blood, saliva, stool, serum, and so on. - Correlation ...
(Date:2/11/2016)...  Kindred Biosciences, Inc. (NASDAQ: KIN ), a ... of pets, today announced the submission to FDA of ... Application (NADA) for Zimeta™ (dipyrone injection, KIND-012).  Positive topline ... for the control of pyrexia (fever) in horses were ... --> The Chemistry, Manufacturing, and Controls ...
(Date:2/11/2016)... 11, 2016 Potrero Medical, Inc., the developer of ... the appointment of George M. Rapier, III , MD, ... TX , WellMed is one of the nation,s largest ... HMO members in Texas and ... of his own internal medicine practice, he has been instrumental ...
Breaking Medicine Technology: