Navigation Links
VCU Massey first to combine targeted agents to kill multiple myeloma cells
Date:2/10/2011

Richmond, Va. (Feb. 10, 2011) Scientists at Virginia Commonwealth University Massey Cancer Center have developed a novel treatment strategy for multiple myeloma that pairs two targeted agents to kill cancer cells. The study's findings, published in today's edition of the journal "Blood," are the first to demonstrate the synergistic, anti-myeloma effects of this combination regimen both in vitro and in vivo.

Multiple myeloma is a cancer involving antibody-producing cells in the bone marrow, and, in most cases, is incurable. Targeted therapies work by interfering with biological and biochemical functions critical for cancer cell survival and proliferation. The new treatment strategy from VCU Massey combines Src inhibitors, which block the activity of an important group of proteins that regulate cancer cell behavior, with Chk1 inhibitors, which interfere with cancer cells' ability to undergo cell cycle arrest and repair DNA damage.

"Chk1 inhibitors are currently used primarily in conjunction with conventional DNA-damaging chemotherapeutic agents," says the study's lead investigator Steven Grant, M.D., associate director for translational research, Shirley Carter and Sture Gordon Olsson Chair in Oncology Research and professor of internal medicine at VCU Massey Cancer Center. "By combining Chk1 inhibitors with another targeted agent, such as Src inhibitors, we were able to induce cell death in multiple myeloma cells while sparing healthy, normal cells."

When multiple myeloma cells are subjected to DNA-damaging agents, or even when they are undergoing normal DNA replication, their DNA is subject to breakage. To survive, they must slow down their progression through the cell cycle in order to repair the DNA, or, if the damage is too severe, undergo a form of cell suicide.

Chk1 is an enzyme that allows cells to undergo cell cycle arrest, a process required to repair the DNA damage. When cancer cells are exposed to Chk1 inhibitors, they experience DNA damage and, as a consequence, launch another defense mechanism by activating a protein known as ERK1/2.

"The activation of ERK1/2 explains why multiple myeloma cells are able to survive the lethal effects of Chk1 inhibitors," says Grant. "Therefore, we used Src inhibitors to block the activation of ERK1/2." The results were more promising than even the researchers had hoped.

Grant's team discovered that Src inhibitors not only blocked ERK1/2 activation, but also synergized with Chk1 inhibitors to trigger a dramatic increase in cell death. In addition, the combined treatment greatly reduced blood vessel formation, which plays an important role in the maintenance of many tumors, including multiple myeloma. Significantly, the treatment exerted virtually no effects on healthy, normal cells.

"We found tumors treated with the combined regimen were noticeably smaller and showed signs of a lack of blood supply when compared to tumors from the control group or those treated only with Chk1 inhibitors," says Grant. "This study is not only the first to demonstrate that Src inhibitors can dramatically increase the effects of Chk1 inhibitors, but it is also the first to show that preventing blood vessel formation may contribute to the effectiveness of this combination strategy."

This study builds upon more than seven years of research by Grant's team investigating cell signaling in relation to DNA damage repair and survival pathways involving Src and ERK1/2 proteins. The researchers are now developing more complex experiments as a prelude to clinical trials in multiple myeloma patients. "We're hopeful the approach of combining targeted agents will open up the possibility of developing entirely new therapies for patients with multiple myeloma and potentially other blood cancers," says Grant.


'/>"/>

Contact: John Wallace
wallacej@vcu.edu
804-628-1550
Virginia Commonwealth University
Source:Eurekalert

Related medicine news :

1. Novel therapy for metastatic kidney cancer developed at VCU Massey Cancer Center
2. VCU Massey Cancer Center awarded $2.4 million grant from Virginia Tobacco Commission
3. Key leukemia defense mechanism discovered by VCU Massey Cancer Center
4. VCU Massey research finds new link between inflammation and cancer
5. When first-time mothers are induced, breaking the amniotic membrane shortens delivery time
6. First Look at Prostate Cancer Genome Yields Insights
7. First Lady Says President Obama Has Quit Smoking
8. FDA Approves First Pacemaker Deemed Safe During MRIs
9. FDA Approves First Drug to Prevent Premature Births
10. HPV vaccine works for boys: Study shows first clear benefits
11. UofL awarded $9.56 million to form first-ever multicenter cardiovascular research network
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/15/2017)... ... 2017 , ... The city of Los Angeles is a west coast style fashion center as ... Style List, a website that spotlights fashion news from Los Angeles and around the world, ... long. , According to the senior editor of latsl.com , “For a business that ...
(Date:8/15/2017)... ... August 15, 2017 , ... Horizon Goodwill ... McCain said, “We are overwhelmed with gratitude for the very generous donation from ... need assistance to both get a job and keep it. This donation will ...
(Date:8/15/2017)... ... August 15, 2017 , ... Progressive Dental, a leading dental marketing ... 2017 Fast 50 list of Fastest Growing Companies in Tampa Bay. The Tampa Bay ... has shown three consecutive years of growth. For this year’s award, Progressive Dental ranked ...
(Date:8/15/2017)... ... August 15, 2017 , ... ... announced today the introduction of the innovative new 10x10 bladder pad ( isocomforter.com/product/10x10-sterile-pad/ ... The plush design enhances comfort and enables the patient to enjoy the benefits ...
(Date:8/15/2017)... , ... August 15, 2017 , ... ... referral for Snap-on Smile® consultations. Patients interested in orthodontics, dental crowns and ... option. Dr. Nash provides Snap-on Smile treatment at his state-of-the-art practice, Nash Family ...
Breaking Medicine News(10 mins):
(Date:8/11/2017)... Israel , Aug. 11, 2017 DarioHealth ... with mobile health and big data solutions, today announced ... on Monday, August 14 and host a conference call ... quarter 2017 operating and financial results and its strategy ... will be hosted by Erez Raphael , Chief ...
(Date:8/7/2017)... , Aug. 7, 2017 Insightin Health, ... acquisition, retention, and engagement, announced the selection of ... and Product Development, effective as of February 2017. In ... technology implementation strategy for our clients. Wood brings ... in consulting and business analytics within the healthcare ...
(Date:8/7/2017)... 7, 2017  Endo International plc (NASDAQ: ... resolve virtually all known U.S. mesh product liability claims ... the known remaining U.S. claims at reasonable values. Under ... the fourth quarter of 2017 and continuing through the ... quarter 2017 results, the Company intends to increase its ...
Breaking Medicine Technology: