24-hour Test Predicts Breast Cancer's Likely Response To Chemotherapy

[News]

A new test has been developed which can predict whether a breast cancer patient will respond to chemotherapy within 24-hours of starting treatment, thus sparing her unnecessary treatment and side effects, according to a study published in the medical journal Clinical Cancer Research...

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[gdpawel]

The idea of searching for clinical responders by testing for a single protein seems nice, but you may have to test for dozens of protein expressions that may be involved in determining sensitivity/resistance to a given drug. Because if you miss just one, that might be the one which continues cancer growth.

The aim here (protein expression), in regards to chemotherapy selection, is to tell if there is a throretical predisposition to drug response. The goal is to look for patterns of normal and abnormal expression which could "suggest" that certain proteins might or might not be produced within a cell. Just because a gene is present, it does not mean that an associated protein has been produced.

So you test one step further to see if the relevant protein actually has been produced. However, even protein testing cannot tell us if a protein is "functional" or how it will interact with other proteins in the presence of conventional or targeted anti-cancer drugs.

Functional profiling tests not only for the presence of genes and proteins but also for their functionality, for their interaction with other genes, proteins and processes occurring within the cell, and for their response to targeted anti-cancer drugs. It measures genes and proteins before and after drug exposure, before putting the anti-cancer drug into the patient.

Functional profiling allows the identification of clinically relevant gene/protein expression patterns which correlate with clinical drug sensitivity and resistance for different drugs in specific diseases. There is no single gene/protein whose expression accurately predicts outcome.

Functional profiling 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, measuring the interaction of the entire genome.

The original Human Genome Project dealth with a homogeneous population of normal diploid cells. This is different from primary tumors, which are heterogeneous and have a genomic signature unique to each and every patient. Functional profiling is a biomarker of heterogeneous cancer cells and genomic signatures unique to every individual patient.

[Rich66]

Abstract

May not be the best test available..but quick and likely better guidance than random chemo selection:

Low RAD51 score was strongly predictive of pathological complete response to chemotherapy, with 33% low RAD51 score cancers achieving pathological complete response compared to 3% of other cancers (p=0.011).

It's all relative to guessing.....

I do like the idea that these coming PARP inhibitors may be useful outside their initial boundaries...(more tools please)

[gdpawel]

A challenge is to identify which of the PARP (enzyme) inhibitor combinations will be effective. What better way than using a cell-based functional profiling assay to identify a potential target population of breast cancer patients that a PARP inhibitor manufacturer thinks will benefit from the drug (and combinations with it) and then conduct a randomized clinical trial among this group.

With so many new targeted drugs on the market today and in the pipeline, it is a big challenge is to identify which of the targeted treatments will be effective (enzyme [PARP] inhibitors, proteasome inhibitors, angiogenesis inhibitors, and monoclonal antibodies), for patients going into clinical trials, or patients' treatment as a result of a clinical trial (community oncology).

Despite its allure, the "genetic" pathway is not all that personalized. Treatment based on "genetic profile" is still a guessing game. That part is still lone in the future, in dealing with proper "drug selection." However, a treatment regimen based on a "functional profile" (a real-time test of treatment on the actual cancer tissue) can predict with accuracy an individual's response to treatment.