Tumor test results are in -- any info or advice?

[lpas]

So I got the results of my Foundation One testing today. Not very uplifting. Apparently, I have 7 mutations and none of them sound good. Here's the rundown:

KRAS - (A146T)
"indicates against the use of cetuximab and panitumumab"

ERBB2 - (amplification)
"associated with resistance to EGFR targeted antibodies in CRC"

TOP2A -(amplification)
"associated with high stage and decreased overall survival in prostate cancer patients"

TP53 - (R248Q, splice site 919+1G>A)
"common in aggressive, advanced cancers"

NOTCH2 - (truncation)
"predicts adverse prognosis and is significantly associated with poor overall survival"

SMAD4 - (loss)
"a marker of poor prognosis and worse relapse-free survival and overall survival in CRC patients."
"strongly correlated with lymph node metastases"

CDK12 - (rearrangment)
"may sensitize cells to PARP inhibitors"

I know the KRAS and TP53 mutations are somewhat common, but anyone here with any of these others? The SMAD4 and NOTCH2 sound particularly concerning. In addition to the above, I found some info indicating the SMAD4 mutation may be less responsive to 5FU. http://www.banglajol.info/index.php/BJP/article/viewFile/20418/14290

Any additional information or advice on any of this? Supplements that may helpful with any of these specific mutations?

Thanks in advance.

[Mastan]

I am not intimately familiar with all of these mutations but the KRAS mutation takes Erbitux off the table as a chemo option. That (KRAS wild type or mutant) is the major diffrentiator between the two most common forms of CRC adenocarcinoma. As such, we have one less chemo option. So my philosophy is to cut or burn it out so that one reduces the tumor volume which then places a lower burden on the chemo. The reality is that there are not that many well established chemo options for CRC. We can hope for new breakthroughs in chemo and immunotherapy. Honestly, the availabilty of treatment drugs is driven by profit rather than by altruism to help humanity. If a drug is found to have potential all the money is poured into its development to potentially recoup the high cost of drug research. If I were a drug company driven by profit I would look to attack the cancer which affects the largest number of people. That is lung cancer. CRC is a distant second if one considers both sexes.

[GrouseMan]

Honestly, the availabilty of treatment drugs is driven by profit rather than by altruism to help humanity. If a drug is found to have potential all the money is poured into its development to potentially recoup the high cost of drug research. If I were a drug company driven by profit I would look to attack the cancer which affects the largest number of people. That is lung cancer. CRC is a distant second if one considers both sexes.

I wish people would quit saying this BS. Getting an anticancer drug out the door is not trivial. It is very difficult in this climate of having to always best what's already there in trials that at best throw the worst patient populations at you. Avastin which is proving to be very useful in colon cancer treatment, was originally fast tracked and later approved for breast cancer, for which it proved to later not be as effective. But it made it to market, due to those early breast cancer trials. This would likely not have made it at all if the decision to approved it rested on the data from the full breast cancer trial, and we would not have it for use today in CRC.

Most companies go after an indication in Lung Cancer, because it has the greatest unmet need. It's actually easier to show if a given treatment will work or not there vs standard treatment, because everything else pretty much SUCKS. So if something shows even a little bit of promise there, it likely will be approved. Today most of the drugs target molecular processes in a tumors cells. All tumors will generally be effected then by the drugs not just those the company sought approval for, so it's likely they will eventually be used in multiple cancers. This is especially true as treatment is moving from a cancer type basis, to a genetic/molecular biology basis. I can tell you the new Pfizer CDK4/CyclinD drug approved yesterday for aggressive breast cancer will be finding its way to CRC, its that good.

When we work in anticancer drug discovery, in the early stages we throw the new candidates at ALL tumor types, seldom do we initially target one vs another. We might think the drug candidate due to its mechanism of action in a given tumor might be better targeted at that tumor than another, only to find out later it proves to work much better in another because that tumor is driven much stronger by that mechanism than the original, and we didn't know that. So when a company seeks approval for a new anticancer drug its on the basis of what they believe their best chances are getting it to the market. Make no bones about it. If the drug looked to work best in a rare form of cancer, the company would still seek approval. There is still money to be made damn the evil pharma company!

GrouseMan

[Mastan]

Hi,

Are you employed by big pharma? You seem to have some inside knowledge. Despite your reply i would still say that we agree to a large extent. Even to your comment about using a drug that was not originally targeted for a specific cancer but is found to work on a less common cancer simply supports the need to recoup the cost of cancer drug development. The other thing that I did not mention is that its likely big pharma driving research rather than the USG. One would like to think that the USG has a big budget for independent cancer research but it is quite likely that most USG research is funded/ directed by big pharma.

Mark

[momof3]

Well your post went slightly off subject...

Im sorry I don't have any info on all of those things, hopefully someone does. But this being a fairly new thing...the testing, maybe not. Have you or will you have an opportunity to discuss with your doc? My first reaction is this is just more info than I would want to know, but I'm sure it can only help in your treatment.

Wish you well, I hope you get your answers soon.

[skypup]

Just signing in to give you a (((hug))) while you process all this...

[KWT]

I would put them in a file and hope you don't need them again. That's where mine are.

[rp1954]

As a practical matter, your F1 information won't make much immediate treatment difference until you drop the oxaliplatin if you follow conventional oncology on "don't do anything else" tx-wise. Assuming you are still doing ADAPT after oxi-, then will be the question of doing the rest of the Life Extension type menu and/or other alternatives which should mostly work with 5FU/X. You can search various alternatives against all your various biomarkers during the Folfox induction period. The HER2/ErbB2 may be addressed by several flavonoids.

In my eyes, the most important biomarkers at this point are a pre-chemo baseline, plus whatever you got before surgery and any tissue stains from path work you can get. Changes in blood tests are likely what would first show any progression while on or off Folfox/ADAPT and what other adjuncts actually improve your situation. For us, the important investments were not costly, as much as they were early enough despite some dr misleads after surgery. After the initial encounters, we didn't argue with doctors over extra work on blood and basic markers, we paid cash and just did them.