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Double binding sites on tumor target may provide future combination therapy
April 09, 2008PHILADELPHIA - Researchers from the University of Pennsylvania School of Medicine and colleagues at Merck Serono Research in Germany have found that two drugs bind to receptor sites on some tumors in different places at the same time, suggesting the possibility of a new combination therapy for certain types of cancer.
An increasing number of therapies targeting tumors that have proteins called epidermal growth factor receptors (EGFR) sitting on their surface are already being used in the clinic or are in late stages of development. For example, Herceptin is an established treatment for certain types of breast cancer and Erbitux and Vectibix are in use for other types of cancer. An additional drug called matuzumab is in phase II clinical trials.
Three years ago, Kate Ferguson, PhD, Assistant Professor of Physiology, and colleagues determined the precise molecular details of how Erbitux, a colorectal and head and neck cancer drug, binds to its target on cancer cells. EGFR drugs halt cell proliferation by blocking EGFR's molecular doorway, keeping hormones from binding and signaling tumor growth. X-ray crystallography provided a snapshot of the interaction between Erbitux and the extracellular component of the cancer cell's receptors.
As is characteristic of many epithelial cancers - such as cancers of the colon, head and neck, breast, ovary, lung, and pancreas - the surface of cancer cells possess abnormally high levels of EGFR. In a cancer cell, an extracellular hormone binds to the outer piece of EGFR, and causes the inside part to kick off a series of reactions that signal the cancerous cell to replicate and divide.
In the present study, published in Cancer Cell, Ferguson and Merck colleagues found - again using X-ray crystallography -- that matuzumab binds in a different place from Erbitux. Their binding does not overlap, and they can bind to EGFR at the same time.
"These findings imply that a combination therapy using both types of EGFR drugs could be developed and tested," says Ferguson. "This has important implications for the clinical use of matuzumab and for developing new therapies that target EGFR."
University of Pennsylvania School of Medicine
As is characteristic of many epithelial cancers - such as cancers of the colon, head and neck, breast, ovary, lung, and pancreas - the surface of cancer cells possess abnormally high levels of EGFR. In a cancer cell, an extracellular hormone binds to the outer piece of EGFR, and causes the inside part to kick off a series of reactions that signal the cancerous cell to replicate and divide.
In the present study, published in Cancer Cell, Ferguson and Merck colleagues found - again using X-ray crystallography -- that matuzumab binds in a different place from Erbitux. Their binding does not overlap, and they can bind to EGFR at the same time.
"These findings imply that a combination therapy using both types of EGFR drugs could be developed and tested," says Ferguson. "This has important implications for the clinical use of matuzumab and for developing new therapies that target EGFR."
University of Pennsylvania School of Medicine
Combination Therapy Current Events and Combination Therapy News RSSEarly end to key study on benefits of niacin, a B vitamin, in keeping arteries open was premature
Heart experts at Johns Hopkins are calling premature the early halt of a study by researchers at Walter Reed Army Medical Center and Washington Hospital Center on the benefits of combining extended-release niacin, a B vitamin, with cholesterol-lowering statin medications to prevent blood vessel narrowing.
Ineffective monotherapies common in high-burden malarious countries
ACTwatch, a research project led by PSI, in collaboration with the London School of Hygiene and Tropical Medicine, released evidence today that indicates that artemisinin combination therapy, the most effective medicines for treating malaria, continue to have a significantly low presence on the market among populations considered to be most at risk.
'Difficult-to-treat asthma' may be due to difficult-to-treat patients
Difficult-to-treat asthma often may have more to do with patients who do not take their medication as instructed than ineffective medication, according to researchers in Northern Ireland.
Study examines treatment for olfactory loss after viral infection
Treatment with a glucocorticoid medication, either alone or in combination with Ginkgo biloba, appears to significantly improve the sense of smell in individuals with previous olfactory loss due to upper respiratory infections.
Breast tenderness during hormone replacement therapy linked to elevated cancer risk
Women who developed new-onset breast tenderness after starting estrogen plus progestin hormone replacement therapy were at significantly higher risk for developing breast cancer than women on the combination therapy who didn't experience such tenderness, according to a new UCLA study.
Self-monitoring of blood glucose
Diabetes patients should always control their own blood sugar values if this leads to improvements in their treatment.
Diabetes drug kills cancer stem cells in combination treatment in mice
In a one-two punch, a familiar diabetes drug reduced tumors faster and prolonged remission in mice longer than chemotherapy alone by targeting cancer stem cells, Harvard Medical School researchers reported in the September 14 online first edition of Cancer Research, a journal of the American Association for Cancer Research.
Men experience sexual dysfunction during hepatitis C therapy
Sexual impairment is common among men with chronic hepatitis C undergoing antiviral therapy, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute.
Chemotherapy resistance: Checkpoint protein provides armor against cancer drugs
Cell cycle checkpoints act like molecular tripwires for damaged cells, forcing them to pause and take stock.
Hepatitis C virus channels efforts into cell survival
Researchers at the University of Leeds have discovered a previously unknown mechanism that allows the hepatitis C virus (HCV) to remain in the body for decades.
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