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 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 (in the same way that neighbors can share food).
Exciting results have come from studies of multitargeted tyrosine kinase inhibitors, "small" molecules that act on multiple receptors in the cancerous cells, like Tykerb. The trend has away from the monoclonals to the small molecules, a trend in which new predictive tests may be able to hasten.
Some years ago, GSK had supplied some private cell-based assay labs with small molecule Tykerb so they can work out an assay for it before its impending FDA approval. A variety of metabolic and morphologic measurements were used to determine if it was successful at killing a patient's cancer cells.
Functional profiling can discriminate between the activity of different targeted drugs and identify situations in which it is advantageous to combine the targeted drugs with other types of cancer drugs. It measures over 100,000 genes before and after drug exposure. Gene expression profiles measures the gene expression only in the resting state, prior to drug exposure.
Researchers had put enormous efforts into genetic profiling as a way of predicting patient response to targeted therapies. However, no gene-based test as been described that can discriminate differing levels of anti-tumor activity occurring among different targeted therapy drugs. Nor can an available gene-based test identify situations in which it is advantageous to combine a targeted drug with other types of cancer drugs. Functional profiling tests have demonstrated this critical ability.
The pre-test (EGFRx Anti-Tyrosine Kinase Profile) is able to test molecularly-targeted anti-cancer drug therapies like Tykerb, Sutent and Nexavar, becasue of being small molecules. A variety of metabolic (cell metabolism) and morphologic (structure) measurements are used to determine if a specific drug (or drugs) was successful at killing the patient's cancer cells. The functinal profiling method differs from other tests in that it assesses the activity of a drug upon combined effect of all cellular processes 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. Functional profiling measures genes before and after drug exposure. Gene expression profiles measure the gene expression only in the resting state, prior to drug exposure.
Unlike (reversible) Herceptin, which only goes after the Her2 gene, also known as epidermal growth factor receptor (EGFR) type 2, (irreversible) Tykerb goes after Her1 (EGFR) but also Her2 (EGFR type 2). Tykerb irreversibly binds to EGFR and Her2. It works by blocking these receptors, preventing their activation and hopefully inhibiting the unwanted signaling pathways. And Tykerb is a BBB crossing drug.
So, will Tykerb be better than Herceptin? You be the judge.
http://weisenthalcancer.com/Services.html