Mannose possibly enhancing chemo

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chadwick1
Posts: 28
Joined: Sat Oct 13, 2018 9:04 am
Location: Upstate NY

Mannose possibly enhancing chemo

Postby chadwick1 » Tue Dec 04, 2018 12:19 pm

Anyone else see this new Nature paper on the sugar mannose? It looks like there's some evidence that "mannose impairs tumour growth and enhances chemotherapy." Also that "colorectal tumors tend to have especially low levels [of the relevant enzyme] so might be good candidates for initial treatments with the sugar." Very interesting.

News article: https://arstechnica.com/science/2018/11 ... elp-chemo/
Nature abstract: https://www.nature.com/articles/s41586-018-0729-3
DX 2017, 37yo father of two
Stage 3b RC (T3N1bM0) normal CEA, KRAS G12V
Radiation + 5FU
LAR w/ temp loop ileo. 2/33 lymph
FOLFOX, 9 rounds
2018 CT mass in liver & lung
MRI confirms liver, Stage 4
Liver resection
2019 lung nodule shrank, monitor
Lung nodule grew again, resection
2020 CT new lung nodule + 2 lymph nodes
FOLFIRI, good response
2021 pause FOLFIRI, attempt lobectomy, aborted
Radiation to lung

PeterG
Posts: 52
Joined: Tue Feb 03, 2015 12:32 pm

Re: Mannose possibly enhancing chemo

Postby PeterG » Tue Dec 04, 2018 11:45 pm

Saw it. Wondered if it was the miracle cure. Worried about panaceas. Wondered if it could interfere with current treatment.
DX Aug. 2013 Resection 09/13.
08/14 CT : .7 CM pulmonary nodule--& multiple nodules.
03/15 15 dendritic cell vaccine-monthly
05/16 begin 3000 MG Xeloda & Avastin
11-16 shrinkage.”Sstable"
2/2017: Port installed. Begin Folfiri and Avastin
8/2017: Xeloda, Avastin and Iranotican. 3-wk cycle.
2-6-18: small pulmonary embolim—some growth in one pulmonary tumor. Start Xarelto.
2-8-18 : Change of chemo: Xeloda with Oxaliplatin no avastin.
9/2018: Tumor growth. Begin Stivarga.

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GrouseMan
Posts: 888
Joined: Mon Aug 12, 2013 12:30 pm
Location: SE Michigan USA

Re: Mannose possibly enhancing chemo

Postby GrouseMan » Wed Dec 05, 2018 11:33 am

Here is some additional commentary on this from "In The Pipeline": https://blogs.sciencemag.org/pipeline/a ... ent-298184

In The Pipeline is a blog I read daily written by someone engaged in medicinal chemistry discovery. Someone that is doing the same sort of Job I used to do. I commented on that post about my concern that in practice it might be difficult to see practical application of the use of mannose unless the manufactures retool so as not to make up the common chemotherapy agents as IV solutions in D5W (Dextrose). Which is my belief that it might rescue the tumors from this Mannose effect. Individual research pharmacies at some NCI cancer centers might undertake reformulating these agents themselves, but most infusion centers probably would continue to buy their normal supplies.

I remember not long ago a patient pointed out she had difficulty getting her oncologist to not use Dextrose solutions for her as she was having problems adjusting her blood sugar being diabetic. Also excessive use of Insulin might drive some tumor types. PI3K inhibitors in cancer therapy have been a mixed bag in the clinic because their down steam effects it turns out muck around with insulin signaling. Sometime if I can relocate the paper about this I will post more information.

This mannose discovery could very well be a great leap forward for some, but its not going to happen over night. Its going to require some clinical trial work to determine how much mannose to use in people and when is the optimal time to use before the FOLFOX infusion. Also we need to understand if the use of D5W in the Infusion rescues the tumor cells from the mannose treatment and should we instead formulate the infusion solutions with Mannose.

If any of you decide to try this. You should let your oncologist know. And also try to get them to use a saline solution instead of Dextrose if possible in the IV infusions. Additionally - did you know that 5-FU is given as an Alkaline solution of between pH 8.6 and 9.4 adjusted that way with sodium hydroxide? I just found that out today. Never knew that before.

Regards,

GrouseMan
DW 53 dx Jun 2013
CT mets Liver Spleen lung. IVb CEA~110
Jul 2013 Sig Resct
8/13 FolFox,Avastin 12Tx mild sfx, Ongoing 5-FU Avastin every 3 wks.
CEA: good marker
7/7/14 CT Can't see the spleen Mets.
8/16/15 CEA Up, CT new abdominal mets. Iri, 5-FU, Avastin every 2 wks.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
1/17 CEA up again dropped from Trial, Mets growth 4-6 mm in abdomen
5/2/17 Failed second trial, Hospitalized 15 days 5/11. Home Hospice 5/26, at peace 6/4/2017

chadwick1
Posts: 28
Joined: Sat Oct 13, 2018 9:04 am
Location: Upstate NY

Re: Mannose possibly enhancing chemo

Postby chadwick1 » Thu Dec 06, 2018 10:23 am

Thanks for that link and context, GrouseMan, that’s good information. Great point about the IV solutions being in dextrose, I wasn’t aware of that. It sure seems like there's a relatively easy trial in here for a major center to do, using their clout/budget to get some reformulated in mannose to try with half of a group. But regardless you’re right it will certainly take some time before we see this in use (assuming it holds up). Though, from the article you linked:

Mannose is not known to be a problem for humans, either, so I would say that physicians treating patients with colorectal cancer would be well advised to give it a try. I look forward to controlled data on this idea, but for now the risk/reward looks very favorable.
DX 2017, 37yo father of two
Stage 3b RC (T3N1bM0) normal CEA, KRAS G12V
Radiation + 5FU
LAR w/ temp loop ileo. 2/33 lymph
FOLFOX, 9 rounds
2018 CT mass in liver & lung
MRI confirms liver, Stage 4
Liver resection
2019 lung nodule shrank, monitor
Lung nodule grew again, resection
2020 CT new lung nodule + 2 lymph nodes
FOLFIRI, good response
2021 pause FOLFIRI, attempt lobectomy, aborted
Radiation to lung


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