TalkNew Test for Lung Cancer Treatment
Tumor typing - or testing the genetic signature of a cancer - is currently helping doctors distinguish between more aggressive and less agressive cancers. As a result, they can recommend treatment that will be most effective for individual patients. Now, researchers have developed a similar test for lung cancer.
The Lung Metagene Predictor (described in this week’s New England Journal of Medicine) scans non-small cell lung cancer cells’ genetic material for patterns that occur in cancers that are likely to reappear. It is 90 percent accurate, its developers said.
If a patient’s tumor shows such patterns, doctors can prescribe more aggressive treatments that are more likely to prevent a recurrence of cancer.
See Scientific American online for details
Lung cancer is the most common form of cancer, and it’s the number one cancer killer in the States. It also has one of the most easily preventable risk factors: smoking. (More statistics)
I had a fascinating discussion yesterday with geneticist Huijun Ring of UCSF about her current research into the pharmacogenetics and -kinetics of smoking. In the not-so-distant future, there may be a “smoking cessation” genetic panel that will tell us about the way in a person metabolizes nicotine and the medications (such as Zyban) that will be most effective in helping her quit.
Technorati Tags: lung cancer, treatment, genes, genetic test, recurrence, smoking, nicotine, pharmacogenetics, pharmacokinetics, buproprion
April 6th, 2007 at 6:27 pm
The new genomic test - Lung Metagene Predictor - is supposed to tell physicians which lung cancer patients will benefit from chemotherapy and which ones do not need to be unnecessarily exposed to toxic chemotherapy cocktails.
The test doesn’t predict which patients will benefit from chemotherapy (i.e. which patients are chemosensitive). Rather, it’s like the Oncotype Dx test, which identifies patients who are unlikely to have a recurrence if treated with surgery alone. If you aren’t going 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. Also, the test has a 10% false reassurance rate (10% of the good prognosis patients none the less recurred).
A genomic test can help to find out if a cancer patient will benefit from chemotherapy or not, and if they do, Whole Cell Profiling can help see what treatments have the best opportunity of being successful. 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.
Whole Cell Profiling (via Cell Function Analysis) measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. No matter which genes are being affected, Whole Cell Profiling is measuring them through the surrogate of measuring if the cell is alive or dead.
For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn’t tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack.
It doesn’t tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.
One of the most promising new approaches that may deal with early detection of cancer is called Proteomics (Protein Expression Analysis), the study of proteins in the cells, tissues and body fluids. Even before a tumor can be felt, some researchers have found, the tumor begins secreting a distinctive pattern, or fingerprint of proteins. Here, you go beyond genes (DNA, the Genomic Analysis or structure of the human genome) and beyond Gene Expression (the measure of RNA content, like Her2/neu in breast cancer) to measure the actual proteins themselves.
Genomic Analysis is only important insofar as it influences Gene Expression Analysis, which is only important insofar as it influences Protein Expression Analysis (Proteonomics), which is only important insofar as it influences Protein Function Analysis (are proteins active or inactive), which is only important insofar as it influences Cell Function Analysis (cell culture testing), which is only important insofar as it influences Disease Analysis (doing something to treat the patient and then making a measurement on the patient with CT/PET scanning), in that order. There is an inverse hierachy between relevance and ease of measurement.
There are many pathways to altered cellular (forest) function (hence all the different “trees” which correlate in different situations). It serves to validate Whole Cell Profiling. The forest is looked at, and not the trees. Whole Cell Profiling measures what happens at the end (the effects on the forest), rather than the status of the individual trees. Cancer is a complex disease and needs to be attacked on many fronts. The best thing to do is to combine these different tests in ways which make the most sense. The future of cancer therapy will be personalized treatments for individual patients, and will require a combination of novel diagnostics and therapeutics.
Improving cancer patient diagnosis and treatment through a combination of cellular and gene-based testing will offer predictive insight into the nature of an individual’s particular cancer and enable 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.
April 21st, 2008 at 2:24 pm
Lung cancer is one of the most common cancers in the US, accounting for about 15% of all cancer patients. There are also approx or 175,000 new cases every single year. Lung cancer is the top cancer-killer in both men and women alike, in the US. Somthing to think about!