In September of 1998, the FDA approved Herceptin to treat breast cancer after it had become metastatic. Yesterday the FDA approved Herceptin's use for women diagnosed with breast cancer just after surgery. The drug is already widely prescribed for adjuvant therapy even without the FDA's approval, a practice called off-label use. Off-label use means that a prescription drug is being prescribed for a purpose not listed on the product's label. This is a common and acceptable practice by doctors and the Food and Drug Administration.
Clinical trials were conducted that showed women who received Herceptin (trastuzumab) given along with chemotherapy had fewer relapses than those who only received chemotherapy. Twenty to thirty percent of women diagnosed with breast cancer have this genetic alteration of the HER2 gene and could benefit by being treated with Herceptin.
1. Is Tykerb better than Herceptin?
Maybe, for these reasons.
Cells are the most basic structure of the body. Cells make up tissues, and tissues make up organs, such as the lungs or liver. Each cell is surrounded by a membrane, a thin layer that separates the outside of the cell from the inside.
For a cell to perform necessary functions for the body and respond to its surroundings, it needs to communicate with other cells in the body. Communication occurs through chemical messages in a process called signal transduction. The purpose of these signals is to tell the cell what to do, such as when to grow, divide into two new cells, and die.
Targeted cancer therapies use drugs that block the growth and spread of cancer by interfering with specific molecules involved in carcinogenesis (the process by which normal cells become cancer cells) and tumor growth. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than current treatments and less harmful to normal cells.
However, the monoclonal antibodies like Herceptin and Erbitux are "large" molecules. These very large molecules don't have a convenient way of getting access to the large majority of cells. Plus, there is multicellular resistance, the drugs affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside, which are protected from the drug. The cells may pass small molecules back and forth.
Exciting results have come from studies of multitargeted tyrosine kinase inhibitors, "small" molecules that act on multiple receptors in the cancerous cells, like Tykerb and Sutent. Targeted "small-molecule" therapies ruled at the recent annual ASCO meeting of oncologists. The trend is away from the monoclonals to the small molecules, a trend in which a new predictive test may be able to hasten.
The EGFRx™ assay is able to test molecularly-targeted anti-cancer drug therapies like Iressa, Tarceva, Tykerb, Sutent and possibly Nexavar, because of being small molecules. The EGFRx™ assay relies upon a technique known as Whole Cell Profiling, in which living tumor cells are removed from an individual cancer patient and exposed in the laboratory to the new drugs.
Basically, Whole Cell Profiling measures the response of the tumor cells to drug exposure. Following this exposure, it measures both cell metabolism and cell morphology. The effect of drugs on the whole cell, resulting in a cellular response to the drug, measures the interaction of the entire genome.
A variety of metabolic and apoptotic measurements are then used to determine if a specific drug was successful at killing the patient's cancer cells. The whole cell profiling method differs from other tests in that it assesses the activity of a drug upon combined effect of all cellular processes, using several metabolic (cell metabolism) and morphologic (structure) endpoints, at the cell "population" level (rather than at the "single cell" level).
Other tests, such as those which identify DNA or RNA sequences or expression of individual proteins often examine only one component of a much larger, interactive process. Whole Cell Profiling measures genes before and after drug exposure. Gene Expression Profiles measures the gene expression only in the "resting" state, prior to drug exposure.
The EGFRx™ Assay is the only assay that involves direct "visualization" of the cancer cells at endpoint. This allows for accurate assessment of drug activity, discriminates tumor from non-tumor cells, and provides a permanent archival record, which improves quality, serves as control, and assesses dose response in vitro.
Source: http://weisenthal.org/ex_targeted_egfr_kinase.pdf
Posted at 7:49PM on Nov 25th 2006 by Gregory D. Pawelski