KRAS G12V Mutation Question

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NHMike
Posts: 700
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Wed Nov 22, 2017 2:47 pm

I thought that KRAS G12V was more or less the same as the other G12* mutations but it's associated with worse prognosis. A person posted that his wife has this mutation this morning and the prognosis doesn't sound good. I did a search on the forum for G12V and a few of Maia's posts came up for clinical trials. It sounds like you're still in standard treatments so maybe it's a bit early for trials.
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

rp1954
Posts: 1206
Joined: Mon Jun 13, 2011 1:13 am

Re: KRAS G12V Mutation Question

Postby rp1954 » Wed Nov 22, 2017 9:41 pm

This paper's results had G12V as the marker of the most successfully treated line (SW480) )of the mutant CRC cell lines tested (vs LoVo for KRAS G13D and HT29 for BRAF V600E), for mutant CRC cells treated with vitamin C.

IV vitamin C temporarily reaches much higher levels in the arteries and veins but (dehyro)ascorbate levels will be lower perfused and transported further in.

Our viable cell lab's sensitivity tests showed that multiple adjuncts (5FU chemo + 2 natural) were necessary to kill less sensitive cancer cells. It seemed surprising then that the resistant CRC cells were not very -iri or -oxi sensitive even without prior treatment. Tissue labs struggled with mutant cell identification, which I suspect has to do with all that cimetidine and IV vitamin C distorting results with those cells that didn't disintegrate and also yielded less CA19-9. However higher bloodlevels of CA199 are often associated with KRAS/BRAF mutations, where serum CA199 is easier to monitor frequently anyway.

In any case, parallel to your situation before surgery, we used oral chemo (5FU base), IV vitamin C, cimetidine and heavy duty supplements in the run up to surgery. Although we used higher vitamin dosages, this list looks useful (http://catalyticlongevity.org/prepub_archive/Adjuvants-ColorectalCA.pdf, a different list than my usual LEF links). Multiple chemo and supplement ajuncts substantially drove down the most common Kras indicator, CA199, before surgery. In 1-2 months, a working dosage eliminated 85%-95% of the CA19-9 blood level associated with the conglomerated mass that was finally removed. Since then, we also found celebrex very useful to improve oral immunochemo results.
Last edited by rp1954 on Thu Nov 23, 2017 3:02 pm, edited 1 time in total.
watchful, active caregiver for stage IVb CC since early 2010. immuno"Chemo forever," for mCRC

zephyr
Posts: 43
Joined: Thu Aug 18, 2016 7:31 am

Re: KRAS G12V Mutation Question

Postby zephyr » Thu Nov 23, 2017 8:48 am

I don't know if this will help. It won't directly answer your question but it might approach it from another angle. I just learned that my tumor (removed over a year ago) had a KRAS 13 mutation. I've been on chemo for over a year and I was in a pretty dark place a while back; the chemo - everything, really - one day it was just all too much. I followed up on a recommendation from another CRC patient to see a naturopathic doc who specialized in oncology. Her goal was to build my immune system and help me manage the chemo side effects; my oncologist was familiar with her practice and fully supportive. She started giving me vitamin C by IV and I started feeling better almost immediately. The next chemo round was noticeably easier, the one after that even better, and I began to feel that she had given me back my life. I can tell my immune system is back in the game; I'm feeling better, I'm healing faster, I'm sleeping better, and I've pulled out of a depression that was beginning to scare me. When I handed her a copy of the genetic testing report earlier this week, she commented that vitamin C targets KRAS. I also noticed on the printed recommendations she gave me after our first visit that IV vitamin C is synergistic with 5FU. As a disclaimer, I'm also on a handful of other supplements, as well as mistletoe injections. I believe all are contributing to my overall mental and physical health, but also that vitamin C was the game changer. Other cancer patients I've met, my IV-chair buddies, have expressed similar feelings. The only side effect we've noticed is that sometimes you feel a bit high after an infusion, not goofy-high just happy and energetic. Maybe euphoric is a better word.

How is all this affecting what remains of my cancer? Don't know but I have another scan in 2 weeks. It might be too soon to notice much difference but ... fingers crossed. Even if I don't show improvement this time around, the change in my quality of life is worth it.

I'm not trying to give anyone medical advice, just relating my own experience is case it's beneficial to someone else. Your mileage may vary. :wink:
Oct-09 Stage I CC
Jun-16 Stage III (T3 N1c)
Jun-16 Surgery
Jul-16 Probable Stage IV with inoperable lung mets
Aug-16 FOLFOX
Jan-17 Dropped Oxi, continuing with 5FU & Avastin
Aug-17 Dropped Avastin, continuing with 5FU
Dec-17 Chemo stopped, lung mets growing but CEA stable, considering other treatment options

NHMike
Posts: 700
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Thu Nov 23, 2017 9:59 am

rp1954 wrote:This paper's results had G12V as the marker of the most successfully treated line (SW480) )of the mutant CRC cell lines tested (vs LoVo for KRAS G13D and HT29 for BRAF V600E), for mutant CRC cells treated with vitamin C.

IV vitamin C temporarily reaches much higher levels in the arteries and veins but (dehyro)ascorbate levels will be lower perfused and transported further in.

Our viable cell lab's sensitivity tests showed that multiple adjuncts (5FU chemo + 2 natural) were necessary to kill less sensitive cancer cells. It seemed surprising then that the resistant CRC cells were not very -iri or -oxi sensitive even without prior treatment. Tissue labs struggled with mutant cell identification, which I suspect has to do with all that cimetidine and IV vitamin C distorting results with those cells that didn't disintegrate and also yielded less CA19-9. However higher bloodlevels of CA199 are often associated with KRAS/BRAF mutations, where serum CA199 is easier to monitor frequently anyway.

In any case, parallel to your situation before surgery, we used oral chemo (5FU base), IV vitamin C, cimetidine and heavy duty supplements in the run up to surgery. Although we used higher vitamin dosages, this list looks useful (a different list than my usual LEF links). Multiple chemo and supplement ajuncts substantially drove down the most common Kras indicator, CA199, before surgery. In 1-2 months, a working dosage eliminated 85%-95% of the CA19-9 blood level associated with the conglomerated mass that was finally removed. Since then, we also found celebrex very useful to improve oral immunochemo results.


I've added a few IV Vitamin C links to papers on this subject to my CRC Cancer page to look at. I'll bring it up with the Oncologist next week. I have a friend using it and she has G12A and said that it helps so it's got my interest.
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

NHMike
Posts: 700
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Thu Nov 23, 2017 10:04 am

zephyr wrote:I don't know if this will help. It won't directly answer your question but it might approach it from another angle. I just learned that my tumor (removed over a year ago) had a KRAS 13 mutation. I've been on chemo for over a year and I was in a pretty dark place a while back; the chemo - everything, really - one day it was just all too much. I followed up on a recommendation from another CRC patient to see a naturopathic doc who specialized in oncology. Her goal was to build my immune system and help me manage the chemo side effects; my oncologist was familiar with her practice and fully supportive. She started giving me vitamin C by IV and I started feeling better almost immediately. The next chemo round was noticeably easier, the one after that even better, and I began to feel that she had given me back my life. I can tell my immune system is back in the game; I'm feeling better, I'm healing faster, I'm sleeping better, and I've pulled out of a depression that was beginning to scare me. When I handed her a copy of the genetic testing report earlier this week, she commented that vitamin C targets KRAS. I also noticed on the printed recommendations she gave me after our first visit that IV vitamin C is synergistic with 5FU. As a disclaimer, I'm also on a handful of other supplements, as well as mistletoe injections. I believe all are contributing to my overall mental and physical health, but also that vitamin C was the game changer. Other cancer patients I've met, my IV-chair buddies, have expressed similar feelings. The only side effect we've noticed is that sometimes you feel a bit high after an infusion, not goofy-high just happy and energetic. Maybe euphoric is a better word.

How is all this affecting what remains of my cancer? Don't know but I have another scan in 2 weeks. It might be too soon to notice much difference but ... fingers crossed. Even if I don't show improvement this time around, the change in my quality of life is worth it.

I'm not trying to give anyone medical advice, just relating my own experience is case it's beneficial to someone else. Your mileage may vary. :wink:


I want to talk to a similar person soon on this stuff. I already have his name and webpage - it will just be about working out an appointment (he's an hour+ away in Boston). I've heard overall good results. This particular guy is a doctor that had cancer himself and he helps cancer patients. My sister mentioned him to me as two of her stage 4 friends use his services.

I looked through the KRAS 13 mutations and didn't see anything bad like BRAF V600E and G12V but do you know your mutation? There are six listed on the MGH Targeted Cancer page and I didn't see major issues with them.
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

zephyr
Posts: 43
Joined: Thu Aug 18, 2016 7:31 am

Re: KRAS G12V Mutation Question

Postby zephyr » Thu Nov 23, 2017 12:05 pm

NHMike wrote:I looked through the KRAS 13 mutations and didn't see anything bad like BRAF V600E and G12V but do you know your mutation? There are six listed on the MGH Targeted Cancer page and I didn't see major issues with them.


Mine was G13D but I got the feeling that she was talking about KRAS generally, not just my particular mutation.
Oct-09 Stage I CC
Jun-16 Stage III (T3 N1c)
Jun-16 Surgery
Jul-16 Probable Stage IV with inoperable lung mets
Aug-16 FOLFOX
Jan-17 Dropped Oxi, continuing with 5FU & Avastin
Aug-17 Dropped Avastin, continuing with 5FU
Dec-17 Chemo stopped, lung mets growing but CEA stable, considering other treatment options

NHMike
Posts: 700
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Tue Nov 28, 2017 2:42 pm

I found a paper on a new approach for Immunotherapy for G12D (which is what I have). There was a NY Times article along with several other articles on this approach. It appears that this approach can also be used for G12V. The belief in the past is that there wasn't a marker on the cell surface for KRAS but that apparently is no longer true. Here's a poster image of the science.

https://pbs.twimg.com/media/CgbOEKEUMAANFL5.jpg

Poster from #AACR16 NCI Human TCRs for KRAS-G12D & KRAS-G12V. HLA-A1101 "Trial will be starting soon". CRC & Panc Ca
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

SweetC80
Posts: 72
Joined: Fri Sep 01, 2017 1:28 pm

Re: KRAS G12V Mutation Question

Postby SweetC80 » Wed Nov 29, 2017 9:07 am

This is really interesting. I never thought to look into my mom's specific type of mutation. I've looked back at her pathology and see it is G12C, so I'm off to research.
My Mom
12/16 Stage IIIb Rectal Ca CEA 1.2
1/17-2/17 Chemoradiation CEA 4.4
5/17 Entire Colon, Rectum & Anus removed Perm Ileostomy Bag
7/17 FOLFOX
9/17 Stage IVb 9cm Liver Met & 7mm Lung Nodule CEA 197
9/17 Irincotecan CEA 160
10/17 Confirmed KRAS Pos CEA 210
11/17 Met growths, Liver 10cm & Lung 8mm CEA 425
12/17 Onco Apt to discuss options after treatment for abscess. Mom's not giving up

NHMike
Posts: 700
Joined: Fri Jul 21, 2017 3:43 am

Re: KRAS G12V Mutation Question

Postby NHMike » Thu Nov 30, 2017 9:35 am

SweetC80 wrote:This is really interesting. I never thought to look into my mom's specific type of mutation. I've looked back at her pathology and see it is G12C, so I'm off to research.


I just tried a Twitter search for KRAS G12C and there has been developmental work on this mutation this past year. The research seems interesting but all of the articles about it are behind paywalls.

Here's an example:

http://www.sciencedirect.com/science/ar ... 5617302313
6/23/17: ER rectal bleeding; Colonoscopy+Biopsy
7/13: Stage 3B rectal cancer. T3, N1b, M0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6 mm, 5 x 5 mm
7/31-9/8: Xeloda 3,400 mg/day+radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8. 11/30: 0.6
MSS, KRAS G12D
10/6: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 mm (-75%), 5 x 3 mm (-40%). 5.1 CM from AV
10/30: Surgery: LAR, Temp Ileostomy
Path report: Tumor regression grade: 0 (complete response).

SweetC80
Posts: 72
Joined: Fri Sep 01, 2017 1:28 pm

Re: KRAS G12V Mutation Question

Postby SweetC80 » Thu Nov 30, 2017 10:59 am

NHMike wrote:
SweetC80 wrote:This is really interesting. I never thought to look into my mom's specific type of mutation. I've looked back at her pathology and see it is G12C, so I'm off to research.


I just tried a Twitter search for KRAS G12C and there has been developmental work on this mutation this past year. The research seems interesting but all of the articles about it are behind paywalls.

Here's an example:

http://www.sciencedirect.com/science/ar ... 5617302313


Thank you!!
My Mom
12/16 Stage IIIb Rectal Ca CEA 1.2
1/17-2/17 Chemoradiation CEA 4.4
5/17 Entire Colon, Rectum & Anus removed Perm Ileostomy Bag
7/17 FOLFOX
9/17 Stage IVb 9cm Liver Met & 7mm Lung Nodule CEA 197
9/17 Irincotecan CEA 160
10/17 Confirmed KRAS Pos CEA 210
11/17 Met growths, Liver 10cm & Lung 8mm CEA 425
12/17 Onco Apt to discuss options after treatment for abscess. Mom's not giving up


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