Molecular profiling from Caris Diagnostics was utilized to determine the course of treatment for each patient with different types of cancers. For breast cancer the period of progression-free survival increased 44 percent, so overall the question of whether or not personalized medicine works seems to have been answered in this study. BD
TGen, Scottsdale Healthcare and Caris Dx clinical trial shows molecular profiling can result in specific treatments for individual patients that significantly limit the growth and spread of tumors
PHOENIX, Ariz. - April 19, 2009 - Cancer patients can survive longer under treatments based on their individual genetic profiles, according to a nationwide study released jointly today by Phoenix-area healthcare organizations.
The study shows that molecular profiling of patients can identify specific treatments for individuals, helping keep their cancer in check for significantly longer periods, and in some cases even shrinking tumors. The study included 66 patients at nine centers across the United States, including Scottsdale Healthcare. Dr. Von Hoff also is the Chief Scientific Officer of TGen Clinical Research Services (TCRS) at Scottsdale Healthcare, a partnership between TGen and Scottsdale Healthcare that is administered by the Scottsdale Clinical Research Institute (SCRI) at Scottsdale Healthcare.
TGen News - Personalized medicine helps cancer patients survive
The benefits of the newer targeted therapies are marginal. These targeted therapies may impart a clinical benefit by stabilizing tumors, rather than shrinking them (substituting shrinkage for stabilization). Targeted therapies need approaches to determine optimal dosing, to assess patient adherence to therapy, and to evaluate treatment effectiveness.ReplyDelete
What would be more beneficial is to test pharmacodynamic endpoints with the ability to measure multiple parameters in cellular screens now in hand using flow cytometry. Using a systems biology approach where compounds are first screened in cell-based assays, with mechanistic understanding of the target coming only after validation of its impact on the biology.
Unlike a test for the presence of receptors to a specific antigen, which only "implies" dependence upon that antigen, a functional assay actually assesses the direct or indirect effect of the drug upon the whole cell, whether it is a tumor cell or an endothelial cell. Genetic analysis happens to test for one molecule which has been implicated in the process but there may be more.
If there were to be only protein involved, then one would expect that gene profiling expression would correlate with activity 100% of the time but it actually does so only about 20% of the time. The functional assay doesn't just focus on any one protein or mechanism. Whether it's one protein alone (unlikely) or in combination with other proteins and other mechanical factors, the assay works by assessing the net effect of all those factors.
Many of these drugs cry out for validated clinical biomarkers to help set dosage and select people likely to respond. And optimal and reproducible gene expression testing continues to evade the diagnositcs of the disease. Numerous other genes, tumor, and patient factors contribute to the risk of the cancer coming back and the effectiveness of chemotherapy for solid tumors.
It could be vastly more beneficial to measure the net effect of all processes (systems) instead of just individual molecular targets. The cell is a system, an integrated, interacting network of genes, proteins, and other cellular constituents that produce functions. One needs to analyze the systems' response to drug treatments, not just one or a few targets (pathways/mechanisms).
There are many pathways/mechanisms to the altered cellular (forest) function, hence all the different "trees" which correlate in different situations. Improvement can be made by measuring what happens at the end (the effects on the forest), rather than the status of the indivudal trees.
Thank you for your comments and opinions and I assume you work in the field from the depth of your information.ReplyDelete