Squamous NSCLC Stage 4 & Functional Profiling

As most of you know, this is my father's diagnosis. I ask today if he could have the functional profiling. He oncologist said that no, he could not because of the type of lung cancer he has. His onc (Dr. Dhruva from Georgia Cancer Specialists) said that it isn't possible to complete a functional profile on Squamous. Does anyone have any other options? He tried carbo/taxol chemo and didn't work. Today he began his Taxotere (Docetaxol). Hoping it works...but I would feel better if there were other options I could investigate, too.

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Kayla, all I can suggest is posting at cancergrace.org. Just copy and paste this. Let them know what stage and type and where his mets are, if any. I'm sure you can get some help there with answers. Good luck and take care, Judy

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Kayla my dad tried taxol and it didn't work he is doing taxotere now and it's working. Just hold on to hope lady. Pray and make him smile and he will keep going!!!! Just believe!!!! I wish you the best!!!!

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I am sure Greg will arrive soon! - But I cant see any reason why FP cant be applied to any sort of tumor - my only reservation would/might be risks in obtaining the sample - perhaps he means he doesnt want to go in and get the sample? But as for the testing per-se I can't see why squamous would be differrent (not that I know this - it just doesnt seem to make sense)

I am not actually endorsing any form of profiling (functional/genetic etc), though I am a user of these services.

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p.s. There was some recent evidence that Abraxane worked very well in sqamous NSCLC, but at present that trial can only report response rates, not overall survival, but very impressive none the less.


I am not sure of the status of this drug re funding/insurance re NSCLC

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The onc might not know what functional profiling means and is getting it confsused with genetic testing (which does not hold mush promise for squamous).

Call Rational Therapeutics and they will explain it to you. In all likelihood your onc will be uninformed and even resistant because this is new technology.

If it is at all possible to get a fresh biopsy without too much trauma, DO IT.

My mom passed away this week and she had squamous cell. She went through carbo, taxol, cisplatin, etopside and navelbine and nothing worked. I wish we had done the profiling to find out what WOULD have worked.

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Could someone please share what functional profiling is? Never heard of it. Glad that this combination worked for my husband but if not we would have tried something else for sure.

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In short, fucntional profiling is a tool used by a handful of cutting edge companies that takes a live biopsy of your cancer and does a bunch of tests on it to see what chemos would work best on it - thus sparing the patient from multiple rounds of chemo that may or may not work.

When an ONC chooses a chemo, they are going by statistics and their own personal experience - there is no way to tell for sure if the chemo will work on any particular patient because each person's cancer is unique and there are several different mechanisms involved. Functional profiling doesn't care WHAT those mechanisms are - it just focused on finding what will work to stop them. Functional profiling takes the guesswork out of deciding which chemo to use I guess.

Does that make sense?

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I'll post it straight from Pat-M, who recently presented it as one of the best "laypersons" terminology of it.

[Gene tests attempt to figure out the "recipe" for your cancer. If it turns out that you have a certain mutation, statistically you may be more likely to respond to a particular treatment. But that is only based on statistics - what worked for other people with a similar cancer recipe.

A functional profile assay uses a freshly biopsied piece of your tumor and throws all the various anticancer drug agents at it to see which ones actually cause the most cancer cells to commit suicide (cell death or apoptosis). The drugs are ranked on their actual effectiveness. The most active is the drug you want to go with. It is a "real time" analysis of how your cancer cells are most likely to respond. No statistics and no guessing.

You do have to undergo a tissue biopsy in order to have a big enough sample to be tested. The reason this is important is that cancer cells don't grow in a vacuum. How they live or die has a lot to do with the chemistry and other biological functions that go on in your own body, so the cancer cells must be kept in a cluster and tested alive as if they were still inside you. You would have to arrange the biopsy through your oncologist or other doctor. The sample would then be sent to the lab for testing. It usually takes a week to get the results.

A functional profiling assay helps you and your doctor determine which anticancer drugs will most likely work best for you as an individual. The reason so many people suffer from chemotherapy is that treatment usually follows a "standard protocol" and many patients have to try 2 or 3 kinds before one works, making them sicker in the process.]

I'll just add that functional 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. Functional profiling looks at the entire genome.

Functional profiling 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, functional profiling is measuring them through the surrogate of measuring if the cell is alive or dead.

In this case, functional profiling can analyze all solid tumors, including squamous cell.

A tumor cell amplifies (copies) DNA segments as a result of cell signals. Gene amplification's role in cancer cells, a tumor cell amplifies, or copies, DNA seqments as a result of cell signals. Drug resistance in cancer cells is linked to amplification of the gene that prevents absorption of the chemotherapeutic agent by the cell. Gene and protein tests are better suited for ruling out "inactive" (resistant) drugs than for identifying "active" drugs.

The focal amplification of a gene in a chromosome plays a key role in squamous cell lineage specificity of the disease. The genetic activation of it represents a unique mechanism of lung squamous cell carcinoma.

All the gene 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 one drug is better or worse than some other drug which may target this.

The cell is a system, an intergrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems' response to drug treatments, before you find clinical responders.

Genetic profiles cannot discriminate differing levels of anti-tumor activity occurring among different targeted therapy drugs. Nor can they identify situations in which it advantageous to combine a targeted drug with other types of conventional cancer drugs.

Gene and protein-targeted drugs are poorly-predicted by measuring the ostensible target, but can be well-predicted by measuring the effect of the drug (or combinations of drugs) on the function (is the cell being killed regardless of the mechanism) of live cells.

Also, one gets more accurate information when using intact RNA isolated from "fresh" live tissue than from using degraded RNA, which is present iin paraffin-fixed tissue.

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Two and a half years ago I was diagnosed with squamous cell and given cisplatin/vinoralbean, then carboplatin/taxol along with 40 treatments of IMRT radiation. None of this did anything to the tumor (it even grew) but sure did make me beaten down. Next I had a risky biopsy (my tumor was in my left lung and tucked up by my aorta and pulmonary artery) so that my onc could sent it to a company called T-Gen in Arizona. After two weeks of study they recommended six types of chemo that would work on my particular cancer, and indeed the very first one (Gemzar) reduced the tumor to nothing. After one clear scan and no chemo for 11 months, the cancer came back in three lymph nodes so I got more Gemzar to reduce them as well. Since I now have cancer in multiple nodes, my chemo has been changed to Alimta which is for metastatic cancer maintenance, and I also get Novalis TX radiosurgery to knock out the bigger nodes when they show up. All of this has been very effective on my particular cancer.

Three months ago (two years after my original diagnosis) my onc also sent a piece of the earlier biopsy to the University of Colorado and they studied it for about a month. They came back with their report and I don't even have squamous cell, I have adenocarcinoma! They also tested for genetic mutations and I have one (C-met). I guess this gives me more treatment options, but it also makes me wonder if that is why all of the original treatments didn't work.

I guess the moral of this story is not to give up because other types of chemo could very well help even though the first few treatments did not work. I was very glad I had the genetic testing so you may want to get another docs opinion about this.

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Yes. Examing a patient's DNA can give physicians a lot of information, there is no doubt about it. But as the NCI has concluded recently, it cannot determine treatment plans for patients. Teasing out the genetic patterns associated with particular drug responses involves some intricate and time-consuming scientific detective work. A challenge facing pharmacogenetics (the study or clinical testing of genetic variation) is the number and complexity of interactions a drug has with biological molecules in the body. Variations in many different molecules may influence how someone responds to a medicine. Cancer is very heterogeneous.

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