A 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.
Wafik S. El-Deiry, MD, PhD, American Cancer Society research professor and Rose Dunlap, professor and chief of hematology/oncology, and a team have tested lapatinib, a targeted chemotherapy agent currently approved for breast cancer treatment, in a 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.
“These are therapeutic antibodies that are manufactured very efficiently, and given to patients,” says El-Deiry.
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.
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 up regulates the receptor for the other drug, and maybe now when we combine these two drugs we’ll get an even better synergy between them,” says El-Deiry.
The research was published in Science Translational Medicine.
Release Date: June 8, 2011
Source: Penn State College of Medicine
Filed Under: Drug Discovery
