nonsmallcelllung cancer

missspring

anyone else KRAS positive with G12D mutation? If so, are you also adeno stage 4 and what treatment are you on?

dennycee

There is a guy over on
There is a guy over on Inspire.com who was kras. Maybe try there.

CraiginPA

KRAS-driven adenocarcinoma type of NSCLC
missspring,

KRAS is a "driving mutation" for lung cancer. A person's lung cancer would almost always have only one driving mutation, at least initially, so if KRAS is the one you have then you wouldn't have one of the others like EGFR, ALK, ROS1, or a rarer less-useful one. (And it's harder to juggle two unrelated driving mutations than one, anyway.) A driving mutation is more accurately described as a gene molecular rearrangement (a fusion or a deletion or an insertion), but driving mutation the layman's term that everyone understands.

KRAS is very common, especially among smokers, but is not yet so useful. Researchers have been trying hard for years to find KRAS-targeted drugs that might selectively block the KRAS mutation from functioning, and thereby stop the cancer for a while. Unfortunately they haven't been successful yet with a targeted approach -- KRAS is more complicated or tricky than some simpler ones they've found drugs for, so when they tried to block KRAS they found there were still some breezy doors and windows left open instead of locking things down tight, and it didn't work.

There are a couple of interesting experimental drugs with potential specifically for KRAS, though we don't know how successful they will be. One, ganetespib, showed some interesting early results in a portion of the few KRAS patients in their early trial. Another one I find interesting is a UK lab's discovery that I hope will lead to a good trial in the UK then elsewhere (maybe not within 2 years). Other trials targeted at KRAS try to inhibit KRAS and then add a 2nd or even a 3rd drug to try to close the biggest doors & windows alternate paths around the drug.

Because it's been so hard to target KRAS effectively with a drug, KRAS is usually treated by conventional methods, mainly various kinds of chemo and sometimes radiation or palliative surgery. The odds of any one chemo treatment being effective at shrinking or stalling the cancer can't be predicted; I tend to assume it'd have 50%/50% odds for lack of a better guess; your oncologist might be able to tell you better.

If at some point chemo seems to be getting less and less likely to be effective, you might reach a point when you want to try something experimental like ganetespib or something specifically targeted to people with KRAS-driven lung cancer, or something completely different like an immunotherapy drug. Your oncologist should be able to discuss options with you -- for each thing you consider, ask for their guess of odds of being effective and for how long. I list some of those experimental trials at this site, if you can visit there to see it:
http://www.inspire.com/groups/lung-cancer-survivors/discussion/kras-trial-or-not/#cmnt_3228606
and here's a more general one I made about
https://www.inspire.com/groups/lung-cancer-survivors/discussion/anyone-have-success-with-tarceva-with-kraus/#cmnt_3141724

BTW, if you only have cancer in the pleura and very little elsewhere, I've been wondering if a surgery and photodynamic therapy approach used for mesothelioma might be applicable. I don't know -- you'd have to ask the surgeon involved, Dr. Joe Friedberg a UPenn in Philadelphia. Here's an article about it:
http://articles.philly.com/2012-06-25/news/32394457_1_mesothelioma-lung-cancer-penn-scientists

One more thing: I do recommend you seek an oncologist who specializes exclusively in lung cancer. There is far too much research to keep up on every kind of cancer and also see patients, so narrowing to lung cancer should mean they are more "up' on the latest research and experimental trials.

Best hopes,

Craig in PA

CraiginPA

CraiginPA said:

KRAS-driven adenocarcinoma type of NSCLC
missspring,

KRAS is a "driving mutation" for lung cancer. A person's lung cancer would almost always have only one driving mutation, at least initially, so if KRAS is the one you have then you wouldn't have one of the others like EGFR, ALK, ROS1, or a rarer less-useful one. (And it's harder to juggle two unrelated driving mutations than one, anyway.) A driving mutation is more accurately described as a gene molecular rearrangement (a fusion or a deletion or an insertion), but driving mutation the layman's term that everyone understands.

KRAS is very common, especially among smokers, but is not yet so useful. Researchers have been trying hard for years to find KRAS-targeted drugs that might selectively block the KRAS mutation from functioning, and thereby stop the cancer for a while. Unfortunately they haven't been successful yet with a targeted approach -- KRAS is more complicated or tricky than some simpler ones they've found drugs for, so when they tried to block KRAS they found there were still some breezy doors and windows left open instead of locking things down tight, and it didn't work.

There are a couple of interesting experimental drugs with potential specifically for KRAS, though we don't know how successful they will be. One, ganetespib, showed some interesting early results in a portion of the few KRAS patients in their early trial. Another one I find interesting is a UK lab's discovery that I hope will lead to a good trial in the UK then elsewhere (maybe not within 2 years). Other trials targeted at KRAS try to inhibit KRAS and then add a 2nd or even a 3rd drug to try to close the biggest doors & windows alternate paths around the drug.

Because it's been so hard to target KRAS effectively with a drug, KRAS is usually treated by conventional methods, mainly various kinds of chemo and sometimes radiation or palliative surgery. The odds of any one chemo treatment being effective at shrinking or stalling the cancer can't be predicted; I tend to assume it'd have 50%/50% odds for lack of a better guess; your oncologist might be able to tell you better.

If at some point chemo seems to be getting less and less likely to be effective, you might reach a point when you want to try something experimental like ganetespib or something specifically targeted to people with KRAS-driven lung cancer, or something completely different like an immunotherapy drug. Your oncologist should be able to discuss options with you -- for each thing you consider, ask for their guess of odds of being effective and for how long. I list some of those experimental trials at this site, if you can visit there to see it:
http://www.inspire.com/groups/lung-cancer-survivors/discussion/kras-trial-or-not/#cmnt_3228606
and here's a more general one I made about
https://www.inspire.com/groups/lung-cancer-survivors/discussion/anyone-have-success-with-tarceva-with-kraus/#cmnt_3141724

BTW, if you only have cancer in the pleura and very little elsewhere, I've been wondering if a surgery and photodynamic therapy approach used for mesothelioma might be applicable. I don't know -- you'd have to ask the surgeon involved, Dr. Joe Friedberg a UPenn in Philadelphia. Here's an article about it:
http://articles.philly.com/2012-06-25/news/32394457_1_mesothelioma-lung-cancer-penn-scientists

One more thing: I do recommend you seek an oncologist who specializes exclusively in lung cancer. There is far too much research to keep up on every kind of cancer and also see patients, so narrowing to lung cancer should mean they are more "up' on the latest research and experimental trials.

Best hopes,

Craig in PA

P.S.
P.S.#1, here are clickable versions of those three URL links:

http://www.inspire.com/groups/lung-cancer-survivors/discussion/kras-trial-or-not/#cmnt_3228606

https://www.inspire.com/groups/lung-cancer-survivors/discussion/anyone-have-success-with-tarceva-with-kraus/#cmnt_3141724

http://articles.philly.com/2012-06-25/news/32394457_1_mesothelioma-lung-cancer-penn-scientists

P.S.#2 If your KRAS-driven lung cancer also has EGFR amplification (EGFR getting very busy rather than being a mutation), the EGFR-targeted drug Tarceva (erlotinib) might be useful:
http://www.ncbi.nlm.nih.gov/pubmed/21518819
so it might be worth asking your oncologist if your KRAS-driven cancer also has EGFR amplification.
(Don't be fooled by that article calling KRAS "Kirsten rat sarcoma;" the full name is "V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog," i.e., similar to, not identical to a rat sarcoma mutation.)

Best hopes,

Craig in PA

sleepless in jersey

missspring
Hello I had contacted craiginpa to see what he could offer, with all of his research to see what he could do to help you.
Sleepless