HER2 Support Group Forums - View Single Post - Lapatinib: A competitor or companion to trastuzumab?

gdpawel · 01-27-2010, 07:28 AM

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 functional tumor cell profiling assay is able to test molecularly-targeted anti-cancer drug therapies like Iressa, Tarceva, Tykerb, Sutent and Nexavar, because of being small molecules. The cell-based assay relies upon a technique known as Functional Tumor Cell Profiling, in which living tumor cells are removed from an individual cancer patient and exposed in the laboratory to the new drugs.

Basically, Functional Tumor 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. Functional Tumor 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 Functional Tumor Cell Profiling 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:

Functional profiling with cell culture-based assays for kinase and anti-angiogenic agents Eur J Clin Invest 37 (suppl. 1):60, 2007

Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546)

Tykerb (lapatinib) is one of the first oral agents with the potential to compete directly with the IV drugs which is both a high-volume and high-revenue part of office-based practices.

Although oral tyrosine kinase inhibitors, like Tykerb, offer patients a well-tolerated, conveniently administered alternative to intravenous (IV) therapy, Decisions Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, found that oncologists are not yet ready to use Tykerb as a replacement for Herceptin.

Ninety-one percent of surveyed oncologists stated that intravenous (IV) cancer therapies are more remunerative than oral therapies. And fifty-eight percent of oncologists say they would favor IV Herceptin over oral Tykerb because administration of IV drugs remains an important source of income for their practices.

01-27-2010, 07:28 AM	#8
gdpawel Senior Member Join Date: Aug 2006 Location: Pennsylvania Posts: 1,080	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 functional tumor cell profiling assay is able to test molecularly-targeted anti-cancer drug therapies like Iressa, Tarceva, Tykerb, Sutent and Nexavar, because of being small molecules. The cell-based assay relies upon a technique known as Functional Tumor Cell Profiling, in which living tumor cells are removed from an individual cancer patient and exposed in the laboratory to the new drugs. Basically, Functional Tumor 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. Functional Tumor 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 Functional Tumor Cell Profiling 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: Functional profiling with cell culture-based assays for kinase and anti-angiogenic agents Eur J Clin Invest 37 (suppl. 1):60, 2007 Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546) Tykerb (lapatinib) is one of the first oral agents with the potential to compete directly with the IV drugs which is both a high-volume and high-revenue part of office-based practices. Although oral tyrosine kinase inhibitors, like Tykerb, offer patients a well-tolerated, conveniently administered alternative to intravenous (IV) therapy, Decisions Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, found that oncologists are not yet ready to use Tykerb as a replacement for Herceptin. Ninety-one percent of surveyed oncologists stated that intravenous (IV) cancer therapies are more remunerative than oral therapies. And fifty-eight percent of oncologists say they would favor IV Herceptin over oral Tykerb because administration of IV drugs remains an important source of income for their practices.