By Charles Ying
Special to LiveLung
First, it’s OK to feel sorry for yourself...OK, now stop and let’s get to work. This is the battle of your Life! You are the Commander-in-Chief. You will need all the help you can get.
There is so much stuff out there from diet, herbal, chi, immunotherapy to Holy Water. There’s nothing wrong with any form of treatment as long as it works for you. The thing about this disease, from a Western Medicine perspective, is that it is in the midst of a major transition. Think Infectious Diseases before Alexander Fleming discovered penicillin. Soldiers in WW1 died from infections. The treatment then was blood-letting and cupping. After penicillin and other more targeted antibiotics, we no longer treat infection by blood-letting.
With NSCLC, chemo, radiation, and surgery were the only options. Then came 2003 and the complete mapping of the Human Genome. Now, we’ve learned that NSCLC can be studied by examining what went wrong with the tumor cells at the DNA level. We can develop medicine to block the failed signaling mechanisms that falsely signal cells to divide. Some of those discoveries improve chemo drugs, like Alimta. Most of the others are known as “small molecule” drugs that target tiny, tiny structures on our cell surfaces where things have gone terribly wrong.
Second, let’s say you just found out you have Non Small Cell Lung Cancer (NSCLC). If you never smoked, you have a better chance of having one of the mutations they have a drug for today. That is only 20% of cancer patients. One big group in this subgroup is what everybody has heard of, namely Epidermal Growth Factor Receptor (EGFR) mutations. This is a mistake in the DNA that is the blueprint for creating the EGFR which is a component on the cell surface of many of our cells that receives the stimuli to trigger the cell to divide. Unfortunately, cells with a defective EGF Receptor can think they are getting the stimuli when there are no such stimuli present outside the cell. So the cell divides and since the daughter cells have the same defect, they divide as well and we get a tumor.
By now, you probably know that Tarceva happens to block the Tyrosine Kinase (the antenna part of the EGF Receptor) and mutes the signaling pathway so the cell no longer gets a signal to divide. Tarceva is the first Tyrosine Kinase Inhibitor (TKI) that is proven to work in more than 90% of NSCLC patients WHO TESTED POSITIVE TO EGFR MUTATIONS. Because of the specific ways TKI works (like a Lego piece that plugs into the receptor), it is highly unlikely that if a cell is dividing because of some other mechanism that the EGFR wild type (opposite of mutant) patient will respond to Tarceva.
Bottom Line: Get your Bio-Markers tested. Know what genetic defect caused your tumor cells to divide.
Easier said than done. No lab on Earth today will perform this test. First of all, the list keeps growing because, as of June 2010, they have only found mutations covering a small percentage of NSCLC. These include household names like:
· KRAS
· EGFR
· NF1
· ALK
· BRAF
· ERBB2
· MEK
· MET
· PDGFR
· PIK3CA
· HER2
· ROS
You get the idea. So find a research hospital and ask them how many of these bio-markers they test for. Pay for it, at all possible, no matter what the cost. (I got mine done at Mass General in Boston. I live in Hawaii. You get the idea.) Ideally, get your biopsy at the same hospital that will run the tests. You can get your local hospital to do a CT-guided needle biopsy, which should be relatively painless. Make sure the lab that will be doing the test provides specifics to your pathologist about how to prepare your tissue sample for shipment.
Remember the old Saturday Night skit where John Belushi plays Julia Child and admonished us to “Save the Liver...” while preparing a turkey for Thanksgiving dinner? Well, “Save your biopsy samples.” Have your radiologist doing the biopsy get as much tissue from your tumor as possible. Tell your pathologist to SAVE YOUR TISSUE sample. The reason is, if you are lucky enough to live a year or two down the road, they may discover more mutations that may or may not apply to you. If your tumors are in remission by then, or are too small, too damaged by radiation or chemo to be tested, then otherwise you may not know whether a new drug would help you or not.
Even if you are not EGFR mutant, and Tarceva cannot help you, there are now new drugs like the recent Pfizer drug Crizotinib (formerly PF-02341066) which targets MET and ALK. Now, if you had only been tested for EGFR and it showed no mutations (wild type), and you have no tissue left and have done some radiation and chemo and your tumors are smaller than 2cm, doctors may not be able to harvest enough tissue for another biomarker test. How sad would that be?
Thirdly, make yourself Portable. Research and clinical trials are going on all over the country. Do you want to fight this battle with only the soldiers in your town or do you want to have the best of the best from around the world on your side?
Unfortunate for us, other than Tarceva and Crizotinib, most of the 50+ drugs in development have names like XL184, ARQ197, i.e. they are not yet FDA approved. But they are designed and proven to work in the lab with tumor cells that have certain specific mutations. So if you know you have a certain mutation like T790M or MET, you will be able to find new drugs that target your mutation in various stages of Clinical Trial. The problem is getting onto one of those trials. Unless you live in NYC, Boston, Houston or some major Cancer Research City, you are unlikely to find it in your local hospital; hence, the need to be portable.
From day one, insist on getting all CT scan images on CD. The industry has a standard and any oncologist can read the CT scan CD. Also, it’s best to be consistent and get contrast CT with 64 slice scanner. Anyway, time to get a laptop (Mac, of course because life is too short for Windows). Download the free OsiriX software and learn how to import your CD into the program and be able to navigate OsiriX to find your tumor and be able to take screen capture (cmd-shift-4) images to email your doctors. Get all radiologist reports either on the same CT CD or in computer-readable form and convert to PDF so you can print and forward to new doctors.
Make a paper file with duplicate CDs (I use Toast on Mac to burn duplicate CDs and create bin/cue image files and post it to Dropbox so any oncologist can download my CT scan CD images).
To get into any clinical trial, you basically have to become a patient of the doctor running that trial at that hospital. They will ask for your patient records. You should have a summary page showing dates since initial diagnosis and treatment with dates you had CT scans and the CDs of each scan in that packet. You should be able to put that packet together in an hour on demand and rush that packet to FedEx if needed for next day delivery.
I keep all of that in a USB flash drive I can FedEx to a tech-savvy oncologist. For the rest, I have a folder of reports and CDs I have duplicated and organized in a folder to be FedEx'ed.
OK. So much for Battle preparation. Now, recruit your Army and prepare for Battle!
You may want to watch this video of Professor Lander of MIT talking about the new field of Genomics that is popping out with drugs like Tarceva and Crizotinib for NSCLC. I posted his 2008 talk on my mobileme account. It is a one hour talk to the staff at USC Medical School, so it is a bit technical but you get the gist even if you have not taken high school biology in this century. BTW, Prof. Lander's freshman biology lectures at MIT 7.012 are wonderful to watch and free to download from Apple's iTunesU store. Here's the link to his talk :
http://lander.ying.com
After viewing this, if you missed more than 80% of what he says, then you should brush up on your high-school biology by downloading this lecture series and put it on your iPhone so you can watch it over and over until you get it.
http://deimos3.apple.com/WebObjects/Core.woa/Browse/mit.edu.1299942944
The Lander talk is one hour long so make sure you have a high bandwidth internet connection and make yourself a cup of tea and sit back and enjoy. This is the science behind what will someday cure this dreadful disease. Just hope we all live long enough.
The MIT Freshman Biology class may take you a year or two to digest. But it is a good thing to do when you are in Hospital waiting rooms waiting for blood work or CT scans.
HTH!
Charles Ying, of Kailua, Hawaii, was diagnosed with Stage IIIB NSCLC in January 2008. He passed away less than three months after writing his Tips for Lung Cancer Newbies. To read a tribute published in the Vail Daily about this extraordinary person, click on this link: http://www.vaildaily.com/apps/pbcs.dll/article?AID=/20100929/OBITS/100929763/0/