Breast cancer drug pushes colon cancer cells to their death
A new treatment for colon cancer that combines a chemotherapy agent approved to treat breast cancer and a cancer-fighting antibody is ready for clinical trials, according to Penn State College of Medicine researchers.
More than 150,000 cases of colorectal cancer are diagnosed each year, and about 50,000 people die from colorectal cancer yearly. Currently there are limited chemotherapy treatments for colorectal cancer with little that has been in the pipeline in recent years.
Wafik S. El-Deiry, M.D. Ph.D., American Cancer Society Research Professor and Rose Dunlap Professor and chief of hematology/oncology, and his team have tested lapatinib, a targeted chemotherapy agent currently approved for breast cancer treatment, in a new combination with artificial antibodies that mimic a natural cancer-fighting protein produced in the human body. The monoclonal antibodies mapatumumab and lexatumumab act similarly to TRAIL -- tumor necrosis factor [TNF]-related apoptosis-inducing ligand -- a naturally occurring molecule in the body that tells a cell it is time to die. TRAIL sets a process in motion that targets and shuts down tumor cells and keeps them from spreading.
The TRAIL receptors -- death receptors -- on the cancer cells respond to TRAIL by dying. The artificial antibodies act as surrogates of TRAIL by activating the same signaling pathway resulting in tumor cell death.
The monoclonal antibodies have an advantage over TRAIL because they remain active in the body for a longer period of time. TRAIL receptor antibodies last for less than 30 minutes, while the artificial monoclonal antibodies last for about nine days. Although the antibodies can act similarly to TRAIL, they do not completely substitute for TRAIL and ultimately which one gets used in what situation is still being tested in clinical trials. But for the purpose of these new advances either one works.
Lapatinib increases the amount of "death receptor" protein available for TRAIL to do its job -- killing off cancerous cells -- El-Deiry and his colleagues report in this week's issue of Science Translational Medicine.
The researchers tested the lapatinib and monoclonal antibody combination in mice. Separately, the two treatments did not increase tumor cell suppression -- but when the drugs were administered together, the researcher found that cell death escalated.
"We have discovered a mechanistic basis for combining these drugs that says one drug upregulates the receptor for the other drug, and maybe now when we combine these two drugs we'll get an even better synergy between them," said El-Deiry. "I think that's probably the most exciting result, to be able to provide a molecular rationale for a new treatment combination for difficult-to-treat advanced colorectal cancers."
The Food and Drug Administration approved lapatinib in 2007 for use as a breast cancer chemotherapy. It blocks two specific types of proteins located on tumor cell surfaces from causing tumors to grow. These proteins are a potent way that tumors are signaled to grow -- and if the proteins are blocked, there is one less mechanism for tumors to proliferate. However, in the treatment El-Deiry has proposed, lapatinib would be used off-label by increasing a different tumor cell death-inducing protein to help colon cancer patients.
Provided by Pennsylvania State University
- Researchers find targeted therapy combination overcomes treatment resistance in liver cancer Apr 13, 2008 | not rated yet | 0
- Penn researchers identify new combination therapy that promotes cancer cell death Jul 17, 2007 | not rated yet | 0
- Overcoming tumor resistance to anti-cancer agent TRAIL Mar 22, 2010 | not rated yet | 0
- Scientists find cancer cell defense method Oct 05, 2005 | not rated yet | 0
- Antibody offers new hope against ovarian cancer Apr 12, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
12 hours ago Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
Even while being dragged to its destruction inside a cell, a cancer-promoting growth factor receptor fires away, sending signals that thwart the development of tumor-suppressing microRNAs (miRNAs) before it's dissolved, researchers ...
Cancer 3 minutes ago | not rated yet | 0 |
Treating pediatric leukemia patients with a liposomal formulation of anthracycline-based chemotherapy at a more intense-than-standard dose during initial treatment may result in high survival rates without causing any added ...
Cancer 4 hours ago | not rated yet | 0
Scientists have uncovered a survival mechanism that occurs in breast cells that have just turned premalignant-cells on the cusp between normalcy and cancers-which may lead to new methods of stopping tumors.
Cancer 4 hours ago | not rated yet | 0 |
Frequent heartburn was positively associated with cancers of the throat and vocal cord among nonsmokers and nondrinkers, and the use of antacids, but not prescription medications, had a protective effect, according to data ...
Cancer 5 hours ago | not rated yet | 0
Ethnic background plays a surprisingly large role in how diabetes develops on a cellular level, according to two new studies led by researchers at the Stanford University School of Medicine.
30 minutes ago | not rated yet | 0 |
Cinnamon: Can the red-brown spice with the unmistakable fragrance and variety of uses offer an important benefit? The common baking spice might hold the key to delaying the onset of –– or warding off ...
52 minutes ago | not rated yet | 0 |
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
53 minutes ago | not rated yet | 0 |
Finnish researchers unveiled new data Thursday to link the Pandemrix flu vaccine to a higher risk of the sleeping disorder narcolepsy in adults.
3 minutes ago | not rated yet | 0
UCLA researchers examining outcomes for advanced heart-failure patients over the past two decades have found that, coinciding with the increased availability and use of new therapies, overall mortality has decreased and sudden ...
57 minutes ago | not rated yet | 0
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
57 minutes ago | not rated yet | 0