Navigation Links
New combo of chemo and well-known malaria drug delivers double punch to tumors
Date:2/18/2012

Vancouver, British Columbia - Blocking autophagy -- the process of "self-eating" within cells -- is turning out to be a viable way to enhance the effectiveness of a wide variety of cancer treatments.

Specifically, blocking the action of an acidic inner cell part, which acts like a stomach and chews up proteins for recycling, is the main attack strategy, says Ravi K. Amaravadi, MD, an assistant professor of Medicine at the Perelman School of Medicine and Abramson Cancer Center at the University of Pennsylvania. Amaravadi will give a presentation on the role of autophagy in fighting cancer at the annual American Association for Advancement of Science meeting in Vancouver, British Columbia.

His lab and others have demonstrated that adding hydroxychloroquine (HCQ) an FDA-approved drug used commonly for malaria and rheumatoid arthritis -- to many cancer therapies, including chemotherapy, targeted therapy, radiation, and immunotherapy, can enhance the antitumor activity of these drugs in laboratory models of treatment-resistant cancers, and ongoing clinical trials.

Autophagy is increased in cancer cells. Normally, it is a survival pathway allowing a cell to recycle damaged proteins when it's under stress and reuse the damaged parts to fuel further growth.

Cancer cells might be addicted to autophagy, since this innate response may be a critical means by which the cells survive nutrient limitation and lack of oxygen commonly found within tumors. And, it is likely to explain how some cancer cells evade chemotherapies by using, essentially, a work around.

Nearly 30 phase I and Phase II clinical trials involving HCQ have been launched or are in planning stages in many different malignancies, including melanoma, multiple myeloma, renal cell carcinoma, colon cancer, prostate cancer, breast cancer, and others.

Preliminary results for most of the trials are encouraging. "Our assays performed on human blood and tissue samples indicate that high doses of HCQ are required to block autophagy in patients, and in some cases, such as in a brain tumor trial, these high doses, in combination with specific anticancer agents, can lead to toxicity for the tumor," says Amaravadi. "As the first phase I trials of HCQ are being completed, it is clear that in most cases the high-dose HCQ, in combination with existing cancer therapy, is well tolerated."

Randomized controlled trials using HCQ combinations to truly determine the effectiveness of the approach are planned. While these are being considered, the team will conduct additional laboratory experiments to identify more potent and specific inhibitors of autophagy and to identify biomarkers that can predict which patients are most likely to respond to this approach. To that end, the Amaravadi lab has identified a compound called Lys05, which is 10-fold more potent than HCQ at blocking the cell from giving the cancer cell a source of raw energy.

"While our knowledge of the role of autophagy in cancer is still in its infancy, the opportunity to learn about autophagy, both at the bench and the bedside, could accelerate the translation of basic advances in this field into clinical benefit for patients with cancer," says Amaravadi.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-459-0544
University of Pennsylvania School of Medicine
Source:Eurekalert

Related medicine news :

1. New Drug Combo for Hepatitis C Shows Promise
2. Two New Drug Combos May Fight Advanced Breast Cancers
3. Anti-estrogen combo better than single drug for hormone-sensitive breast cancer
4. Tender Breasts From Combo HRT Linked to Higher Cancer Risk
5. Combo hormone therapy has increased breast cancer risk over estrogen alone
6. New drug combo targets multiple cancers
7. Breast tenderness in women getting combo hormone therapy associated with increase in breast density
8. FDA Approves First Combo Drug for Diabetes, Cholesterol
9. Drug Combo Might Fight Aggressive Breast Cancer More Safely
10. For Some Prostate Cancer Patients, Combo Treatment Improves Survival
11. New Combo Therapy May Prevent TB, Save Lives in People With HIV
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/16/2017)... ... August 16, 2017 , ... ... eBook, 9781498499620    ) shares that during the time of a cancer diagnosis, surgery and ... God's love, and all the many ways God shows love to those who ...
(Date:8/16/2017)... Lake Orion, Rochester, Michigan (PRWEB) , ... August ... ... now offer treatment options to patients suffering from chronic pelvic pain. In ... treatment of various pelvic pain disorders including endometriosis, menorrhagia (abnormal heavy bleeding during ...
(Date:8/16/2017)... ... 16, 2017 , ... With low back pain afflicting 8 of 10 Americans at some point ... – upper back pain. But this equally vexing condition stems from a variety of causes ... Liu, MD, PhD , founder and president of Atlantic Spine Center. , Nestled between ...
(Date:8/15/2017)... ... 15, 2017 , ... Western University of Health Sciences President ... forward in bold new directions while using its foundational values of humanism and ... the traditional opening of the academic year, on August 12, 2017 at Fairplex ...
(Date:8/15/2017)... ... August 15, 2017 , ... An ... who fell into a coma and died after receiving silicone injections for buttock ... performed in the alleged perpetrator’s apartment after the victim was fetched from a ...
Breaking Medicine News(10 mins):
(Date:8/7/2017)... , Aug. 7, 2017 Diplomat Pharmacy, Inc. ... Joel Saban as president, effective Aug. 7, 2017. ... has decided to pursue other interests and will serve ... his tenure, Paul has served us in multiple leadership roles ... Pharmacy in Jun. 2015 and has provided decisive, strategic leadership ...
(Date:8/4/2017)... , Aug. 3, 2017  Agragen, LLC, ... company active in the biopharmaceutical, nutraceutical, and aquacultural ... development of its lead drug candidates, AGR131.  This ... proinflammatory cytokine from the blood of patients suffering ... and inflammatory bowel disease. ...
(Date:8/2/2017)... 2, 2017  Life Flight Network and PeaceHealth Oregon Network ... patient care and operational efficiency for patients at hospitals in ... Cottage Grove , and Florence, ... and Life Flight Network work collaboratively to move patients who ... when a time sensitive emergency exists. ...
Breaking Medicine Technology: