Enhancing chemotherapy's efficacy: New agent has synergistic effect with standard drugs

April 15, 2007

Integrating the use of drugs targeted to specific cancer proteins into current chemotherapy regimens to improve the efficacy of systemic treatment is an important clinical goal at Fox Chase Cancer Center. Fox Chase research presented during the 97th Annual Meeting of the American Association for Cancer Research in Los Angeles has found that a new chemical agent, MCP110, has a synergistic effect both in vitro and in vivo when used with current chemotherapy drugs such as taxanes (Taxol and Taxotere) and vinca-alkaloid compounds such as vincristine.

This synergistic effect--in which the effect of two agents is greater than the sum of their individual effects--appeared when using the combination of MCP110 and Taxol on laboratory cell cultures of human Kaposi's sarcoma and mouse models carrying human lung and colon cancer cells.

"Together, these findings indicate that MCP compounds have potential to be effective in combination with other anticancer agents," the authors concluded.

Vladimir Khazak, Ph.D., now director of biology at NexusPharma, Inc., in Langhorne, Pa., and formerly a postdoctoral associate in the Fox Chase laboratory of molecular biologist Erica A. Golemis, Ph.D., presented the research in an AACR poster session. The work also appears in the March 1 issue of the AACR journal Molecular Cancer Therapeutics ("In vitro and in vivo synergy of MCP compounds with mitogen-activated protein kinase pathway--and microtubule-targeting inhibitors").

The work builds on prior findings published by the team in the Proceedings of the National Academy of Sciences, which first identified MCP compounds, and demonstrated that MCP compounds have the ability to inhibit the growth of cultured cancer cells that depend on interactions of the Ras and Raf oncogenes--growth-promoting genes that can transform cells to cancerous ones if the oncogene is activated inappropriately.

The growth signals sent by these oncogenes use a well-traveled enzyme pathway called MAPK (mitogen-activated protein kinase). This pathway is responsible for cell response to various growth factors and is involved in the action of many cancer-causing genes.

A number of new cancer drugs in development such as MCP110 target this pathway to inhibit one or more steps in the growth signaling process. However, many established cancer chemotherapy drugs are cytotoxic--cell-killing--drugs that work in different ways, such as damaging their DNA or attacking the cells' architecture. Several widely used drugs, including paclitaxel (Taxol), docetaxel (Taxotere) and long-time standby vincristine, take the latter approach, targeting important cell components called microtubules.

"Very few clinical agents are as successful by themselves as they are in combination," Golemis pointed out. "Combination chemotherapies may use two drugs that either have the same target or two different targets. Another approach--the one we've taken here--is to combine a pathway-targeted drug with conventional chemotherapy.

"We've found that MCP110 synergizes both with other small molecules targeting the MAPK pathway and with multiple cytotoxic drugs. These studies predict that MCP110 is a potentially useful treatment agent for combination chemotherapy." In addition to Khazak and Golemis, co-authors include Fox Chase visiting scientist Natalia Skobeleva, Ph.D., of St. Petersburg Polytechnical Institute in St. Petersburg, Russia, NexusPharma chemistry director Sanjay Menon, Ph.D.(formerly associated with NexusPharma and now at Boehringer Ingelheim Pharmaceuticals, Inc.,), and NexusPharma executive director Lutz Weber, Ph.D.
-end-
NexusPharma, Inc., has entered into general agreements and has licensed intellectual property from Fox Chase that are providing the basis for its protein interaction technology and enabling the discovery and development of novel therapies by modulating protein-protein interactions with small molecules to advance the treatment of cancer through approaches based on non-cytotoxic mechanisms. In addition, the company has entered into a collaborative research agreement with Fox Chase enabling access to its renowned scientific expertise and first-rate research facilities.

A grant from the Ben Franklin Technology Partners of Pennsylvania supports this research along with the cancer-center support grant from the National Institutes of Health and an appropriation from the Commonwealth of Pennsylvania to Fox Chase Cancer Center. Fox Chase Cancer Center was founded in 1904 in Philadelphia as the nation's first cancer hospital. In 1974, Fox Chase became one of the first institutions designated as a National Cancer Institute Comprehensive Cancer Center. Fox Chase conducts basic, clinical, population and translational research; programs of cancer prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at www.fccc.edu or call 1-888-FOX CHASE.

Fox Chase Cancer Center

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.