Tests Could Predict Benefit From Cancer Drugs

[gpawelski]

What if a blood test or biopsy could predict if a cancer therapy will help cure you, or only make you feel worse?

Tests like these, based on genes, proteins or other "molecular markers" may someday do just that for people battling colon, lung and pancreatic tumors, scientists reported at a news conference.

"The ultimate goal is to bring personalized medicine to reality, to identify characteristics of tumors or patients where we can make a relatively dramatic impact using targeted agents," said Dr. Bruce Johnson of the Dana-Farber Cancer Institute and Harvard Medical School, in Boston.

http://health.usnews.com/articles/health/healthday/2008/10/29/tests-could-predict-benefit-from-cancer-drugs.html

[gpawelski]

Genomics are far too limited in scope to encompass the vagaries and complexities of human cancer biology. The human genome project will give way to the human epigenome project which will give way to the human proteome and human kinome project. The next generation of tests will be biosystematic.

If you find one or more implicated genes in a patient’s tumor cells, how do you know if they are functional; is the encoded protein actually produced? If the protein is produced, is it functional? If the protein is functional, how is it interacting with other functional proteins in the cell?

Without the advantage of knowing how cancer cells will respond to a chemotherapy drug before it is administered, physicians face an unmitigated risk that the wrong chemotherapy could further weaken a patient’s immune system while allowing the cancer to continue its progression. Ultimately, use of ineffective drugs during initial therapy may lead to treatment failure.

The most effective use of cytotoxic chemotherapy is in the first-line setting. While some patients present with inherently resistant disease, it is possible that the resistance identified against one "standard" regimen may not be obtained with all regimens.

Functional profiling has the capacity to measure genetic and epigenetic events as a real-time adjunct to static genomic and proteomic testing, by examining small clusters of cancer cells in their native state, which contains all the complex elements of tumor bio-systems found in the human body and have a major impact on clinical response.

It can help make the right choices for patients whether at first-line therapy or thereafter by providing a snapshot of the response of tumor cells to drugs, combinations and targeted therapies.

[Keggy]

This sounds like the Oncotype DX test they have for persons dx with bresast cancer. It assesses the benefit from chemotherapy the likelihood of breast cancer recurrenc.

[gpawelski]

The OncotypeDx test identifies patients who are unlikely to have a recurrence if treated with surgery alone. If you aren't likely to have a recurrence, you don't need chemotherapy. The test doesn't do anything to indicate if chemotherapy would or would not be helpful for those patients at higher risk for recurrence, much less which chemotherapy would be most likely to be helpful.

As far as using a genetic test to select the individual drugs that will best match a tumor's molecular makeup, 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.

All the mutation or amplification studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if drug A is better or worse than drug B which may target this. There are differences. The drug has to get inside the cells in order to target anything.

Targeted drugs are poorly-predicted by measuring the ostansible target, but can be well-predicted by measuring the effect of a drug on the "function" of live cells. A "functional" targeted therapy profile includes analysis of numerous targeted drugs, as well as conventional cytotoxic agents.

Improving cancer patient diagnosis and treatment through a combination of cellular and gene-based testing could offer predictive insight into the nature of an individual's particular cancer and enable medical oncologists to prescribe treatment more in keeping with the heterogeneity of the disease. The biologies are very different and the response to given drugs is very different.

[gpawelski]

In a press release from Harvard’s Dana-Farber Cancer Center, an oncologist announced that they are eager for this technology to be widely available to physicians and their lung cancer patients, as it can help identify those who are likely to dramatically respond and survive for extended periods of time with a relatively benign treatment.

And what are the data which support the value of this new technology to patients? Two entirely retrospective studies, from two Harvard-affiliated hospitals, showing slightly improved response, but not improved survival, with a grand total of 26 assay/treatment correlations.

And yet the Harvard press release reports that fully 50% of Dana Farber lung cancer patients now receive the test and Harvard has licensed it to Genzyme, a huge commercial laboratory which markets it for use in planning treatments for cancer patients, at $1,000 per test.

Meanwhile a different study, by a different institution and published in the New England Journal of Medicine failed to find any correlation at all between gene mutations and patient survival (N Engl J Med Volume 353:133-144, July 14, 2005, Number 2).