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very encouraging CRC genetic test

janderson1964
Posts: 1525
Joined: Oct 2011

Go to news@ccalliance.org. click on Vast gene study raises hopes for colon cancer drugs. The link takes you to a NY Times article after you sit through a Starbucks ad. The study is VERY encouraging.

pete43lost_at_sea's picture
pete43lost_at_sea
Posts: 3915
Joined: Nov 2010

great study

i liked this part.

The hope now is that the genetic alterations driving those 1,000 different tumors are operating through only a limited number of genetic pathways that can be targeted by a more manageable number of drugs.

hugs,
Pete

janderson1964
Posts: 1525
Joined: Oct 2011

I agree. Now lets hope research for a drug to bock this pathway is on going and the FDA puts it on the fast track once a drug is developed

tanstaafl's picture
tanstaafl
Posts: 945
Joined: Oct 2010

The hope now is that the genetic alterations driving those 1,000 different tumors are operating through only a limited number of genetic pathways that can be targeted by a more manageable number of drugs.
...or nutrients and extracts

janderson1964
Posts: 1525
Joined: Oct 2011

Good point.

steved
Posts: 836
Joined: Apr 2004

It is interesting to read of common mutations across different cancers that increases the idea that we shouldn't think of cancers in different organs being that different. The big positive this leads to is the potential use of drugs already used in other cancers- stopping the need for new drugs being developed and approved which takes years.

Unfortunately I have not been able to access the original study which is always the more important read (rather than media releases which are selling papers) in order to assess the real value of the research- anyone else gain access to it?

steve

janderson1964
Posts: 1525
Joined: Oct 2011

I read an article in Cure magazine about a year ago talking about treating cancers based on common genetic mutations rather than where the cancer originated.

pete43lost_at_sea's picture
pete43lost_at_sea
Posts: 3915
Joined: Nov 2010

easy bedtime reading

://www.nature.com/nature/journal/v487/n7407/full/nature11252.html

This comprehensive integrative analysis of 224 colorectal tumour and normal pairs provides a number of insights into the biology of CRC and identifies potential therapeutic targets. To identify possible biological differences in colon and rectum tumours, we found, in the non-hypermutated tumours irrespective of their anatomical origin, the same type of copy number, expression profile, DNA methylation and miRNA changes. Over 94% had a mutation in one or more members of the WNT signalling pathway, predominantly in APC. However, there were some differences between tumours from the right colon and all other sites. Hypermethylation was more common in the right colon, and three-quarters of hypermutated samples came from the same site, although not all of them had MSI (Fig. 2). Why most of the hypermutated samples came from the right colon and why there are two classes of tumours at this site is not known. The origins of the colon from embryonic midgut and hindgut may provide an explanation. As the survival rate of patients with high MSI-related cancers is better and these cancers are hypermutated, mutation rate may be a better prognostic indicator.

Whole-exome sequencing and integrative analysis of genomic data provided further insights into the pathways that are dysregulated in CRC. We found that 93% of non-hypermutated and 97% of hypermutated cases had a deregulated WNT signalling pathway. New findings included recurrent mutations in FAM123B, ARID1A and SOX9 and very high levels of overexpression of the WNT ligand receptor gene FZD10. To our knowledge, SOX9 has not previously been described as frequently mutated in any human cancer. SOX9 is transcriptionally repressed by WNT signalling, and the SOX9 protein has been shown to facilitate β-catenin degradation38. ARID1A is frequently mutated in gynaecological cancers and has been shown to suppress MYC transcription39. Activation of WNT signalling and inactivation of the TGF-β signalling pathway are known to result in activation of MYC. Our mutational and integrative analyses emphasize the critical role of MYC in CRC. We also compared our results with other large-scale analyses6 and found many similarities and few differences in mutated genes (Supplementary Table 3).

Our integrated analysis revealed a diverse set of changes in TCF/LEF-encoding genes, suggesting additional roles for TCF/LEF factors in CRC beyond being passive partners for β-catenin.

Our data suggest a number of therapeutic approaches to CRC. Included are WNT-signalling inhibitors and small-molecule β-catenin inhibitors, which are showing initial promise40, 41, 42. We find that several proteins in the RTK–RAS and PI3K pathways, including IGF2, IGFR, ERBB2, ERBB3, MEK, AKT and MTOR could be targets for inhibition.

Our analyses show that non-hypermutated adenocarcinomas of the colon and rectum are not distinguishable at the genomic level. However, tumours from the right/ascending colon were more likely to be hypermethylated and to have elevated mutation rates than were other CRCs. As has been recognized previously, activation of the WNT signalling pathway and inactivation of the TGF-β signalling pathway, resulting in increased activity of MYC, are nearly ubiquitous events in CRC. Genomic aberrations frequently target the MAPK and PI3K pathways but less frequently target receptor tyrosine kinases. In conclusion, the data presented here provide a useful resource for understanding this deadly disease and identifying possibilities for treating it in a targeted way.

hugs,
pete

janderson1964
Posts: 1525
Joined: Oct 2011

I wanted to bump this up in hopes that more of you will read this article. It is so very encouraging to me. Hopefully this information will give us CRC survivors access to treatments for other cancers SOON as well as lead to new break throughs. Things are looking up for us with the approval of Zaltrap and Regergofenib and hopefully new and more effective targeted therapies not far behind.

coloCan
Posts: 1840
Joined: Oct 2009

http://ecancer.org/news/3321

(with link to abstract of original article,which -the original-can't be accessed unless you're a member of that site-I'm not)

scared99
Posts: 73
Joined: Jun 2012

I really hope any promising new treatments are put on the fast track. It is somewhat agravating to see how long the process is for some of these drugs to get approved.

So Worried
Posts: 111
Joined: Aug 2012

Hello Pete,

So....in plain language are they saying that right sided/ascending tumors are more likely to be hypermutated and those have a better outlook? Or...am I completely way off?

You seem very knowledgeable, so thought I would ask :)

Thank you!!

pete43lost_at_sea's picture
pete43lost_at_sea
Posts: 3915
Joined: Nov 2010

now i am worried,

i reread that part of the study to answer your query.

i had your answer, then i thought i will reread it again.

guess what different answer, so heck i am just as confused about this signalling stuff.

and this is just one scientists opnion, anyway.

to find what works is our goal, my goal for me. so thats dam hard when the goal post moves.

its late, i am jet lagged, maybe after another years study and reading this will make more sense.

i think you are pretty close.

what got my attention was the genetic similarity, suggesting the epigenetic environment is key in carinomgenius.

hugs,
Pete

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