Tests Could Predict Benefit From Cancer Drugs

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.

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).