A new study of mice implanted with human breast cancer cells shows the spread of the disease to the lungs -- a common metastasis site -- is caused by the abnormal activation of four specific genes working together.The study, published in the journal Nature, indicates that shutting off the genes one by one can slow the growth and spread of this cancer. But turning off all four at one time almost completely stops the process. In mice anyway.
These genes are no strangers to researchers who have known for some time about their existence and functions. They just know more about them now.
The four genes work together at every step of the metastatic process to allow a breast tumor to develop blood vessels, let tumor cells enter the vessel walls and lungs, and permit them to pass out of the lung vessels and resume growth. New analysis shows that blocking these genes significantly reduces the tangle of blood vessels, making it harder for cancer cells to escape.
Researchers, who say the four genes are among 18 they associate with breast cancer metastasis, report that one implication of this study is clear: combined use of drug therapy may be more effective at inhibiting the activity of multiple gene targets.
1. While it may be very important to zero in on different genes and proteins, when actually taking these drugs, do the drugs even enter the cancer cell? Once entered, does it immediately get metabolized or pumped out, or does it accumulate? In some cases, these and other drugs, kill tumor cells without killing microvascular cells in the same time frame. In other cases they kill microvascular cells without killing tumor cells. In yet other cases they kill both type of cells or neither type of cells. The ability of these agents to kill tumor and/or microvascular cells in the same tumor specimen is highly variable among the different agents.
There are assays that allow for the study of anti-microvascular drug effects of standard and targeted agents. They are based upon the principle that microvascular (endothelial and associated) cells are present in tumor cell microclusters obtained from solid tumor specimens. The assay which has a morphological endpoint, allows for visualization of both tumor and microvascular cells and direct assessment of both anti-tumor and anti-microvascular drug effect.
Direct visualization of the cancer cells at endpoint allows for accurate assessment of drug activity, discriminates tumor from non-tumor cells, and provides a permanent archival record to improve quality, serve as control and assess dose response in vitro. Photomicrographs show that sometimes clones of tumor cells don't accumulate a drug or combination of drugs. These cells won't get killed by it. The assay can measure the net effect of everything which goes on. Are the cells ultimately killed, or aren't they? Each of the new targeted drugs will not work for everybody. It would be nice to know if they will work for your particular cancer.
Source: Cell Function Analysis
Posted at 6:19PM on Apr 24th 2007 by Gregory D. Pawelski