DK37 Science Posts List

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DK37
Posts: 510
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Location: San Diego

DK37 Science Posts List

Postby DK37 » Tue Oct 20, 2015 10:26 pm

Following a suggestion/request from Nik - here is a list of links to the various science post threads I've started since I started posting on Colon Talk in last 2014.

I'll try (hard) to remember to update it with new links when I make new posts.

Up to you guys if you think it is useful or not... THANK YOU NIK for compiling this starter list for me! It's in chronological order.

Cheers,
-DK

Nov 25, 2014
New CRC Immunotherapy Trial Announced: anti-PD1 + anti-CSF1R
viewtopic.php?f=1&t=48812&p=371077#p371077

Jan 09, 2015
Forbes - Immuno-oncology Story
viewtopic.php?f=1&t=49692&p=377425#p377425

Feb 20, 2015
New CRC Immunotherapy Paper: PD-L1 + ITK Inhibitors
viewtopic.php?f=1&t=50318&p=385011#p385011

Feb 27, 2015
Advance Screening - Emperor of All Maladies (Ken Burns)
viewtopic.php?f=1&t=50399&p=386106#p386106

Mar 16, 2015
New Pilot Clinical Trial Results for BRAF-mut Stage IV CRC
viewtopic.php?f=1&t=50572&p=388522#p388522

Mar 18, 2015
RRx-001 Prelim. Phase 2 Data - Resensitizing Tumors to chemo
viewtopic.php?f=1&t=50598&p=388897#p388897

Mar 23, 2015
Updated RRx-001 Preliminary Phase 2 Trial Data
viewtopic.php?f=1&t=50662&p=389876#p389876

Apr 19, 2015
Johns Hopkins Immunotherapy Paper: 100% CRC cure rate in a poorly immunogenic CRC Mouse Model
viewtopic.php?f=1&t=51103&p=394260#p394260

Apr 25, 2015
New Arizona Trial: Nivolumab (PD-1 Immunotherapy) + XELIRI/Irinotecan
viewtopic.php?f=1&t=51169&p=395429#p395429

Apr 27, 2015
Update on MGD007 Trial – New Sites Open!
viewtopic.php?f=1&t=51205&p=395783#p395783

May 17, 2015
KRAS-wt: Clinical Trial Results for Sym004 (after cetuximab resistance)
viewtopic.php?f=1&t=51417&p=398909#p398909

May 29, 2015
Potential to be Biggest CRC Drug Breakthrough in Years (ASCO Results - PD1 for MMR-deficient CRC)
viewtopic.php?f=1&t=51551&p=400371#p400371

Jun 27, 2015
My Blood Biopsy Story (From Voxx66's News from Dr appt post)
viewtopic.php?f=1&t=51860&p=404644#p404644

Jul 07, 2015
Preliminary Clinical Trial Data for "Xilonix" - Currently in Phase 3 Trials for mCRC
viewtopic.php?f=1&t=51936&p=405574#p405574

Jul 14, 2015
New Monthly DK Column: The Currently Incurable Scientist
viewtopic.php?f=1&t=52004&p=406248#p406248

Jul 24, 2015
The Currently Incurable Scientist: Turning a Cold CRC Tumor Hot
viewtopic.php?f=1&t=52072&p=407081#p407081

Aug 08, 2015
Anti-4-1BB (CD137) Immunotherapy - e.g. Urelumab CRC Trial
viewtopic.php?f=1&t=52176&p=408263#p408263

Aug 13, 2015
The Currently Incurable Scientist: The Future of anti-EGFR Therapy?
viewtopic.php?f=1&t=52242&p=408851#p408851

Aug 18, 2015
Pushing for Lung RFA & the Power of Hope
viewtopic.php?f=1&t=52286&p=409394#p409394

Aug 20, 2015
RRx-001 Phase 1 Clinical Trial Results Published in Lancet Oncology
viewtopic.php?f=1&t=52306&p=409612#p409612

Aug 21, 2015
Anti-Immunosuppression PD-1 Co-therapies for CRC (Reply to Jortego128’s Bavituximab for Rectal Adenocarcinoma... post)
viewtopic.php?f=1&t=52315&p=409674#p409674

Aug 31, 2015
New PD-1 Inhibitor Combo Studies for CRC (All or MSS Specific)
viewtopic.php?f=1&t=52397&p=410649#p410649

Sep 08, 2015
Immunotherapy Suggestion: Add MSI/MSS Status to Your Signature Line (Explained)
viewtopic.php?f=1&t=52480&p=411684#p411684

Sep 15, 2015
Currently Incurable Scientist: Putting out the Inflammation Fire (Xilonix)
viewtopic.php?f=1&t=52534&p=412532#p412532

Sep 22, 2015
TAS-102 FDA Approved!
viewtopic.php?f=1&t=52603&p=413564#p413564

Oct 01, 2015
Neon Therapeutics - TIL ImmunoTherapy
viewtopic.php?f=1&t=52682&p=414496#p414496

Oct 11, 2015
Sneak Peek - Major MSI Education Project
viewtopic.php?f=1&t=52741&p=415285#p415285

Oct 13, 2015
The Currently Incurable Scientist:Releasing the PD-1 Brakes in MSI-High CRC Patients
viewtopic.php?f=1&t=52758&p=415479#p415479

Oct 14, 2015
The Faces of Successful Colorectal Cancer Immunotherapies Vol. 1
viewtopic.php?f=1&t=52772&p=415599#p415599

Oct 17, 2015
FPA008 (anti-CSF1r) + PD-1 Inhibitor Deal Announced (Trial Already Started)
viewtopic.php?f=1&t=52787&p=415815#p415815

Oct 18, 2015
MSS-CRC Immunotherapy Phase 1 Trial at Johns Hopkins (PD-1 + Epigenetic Drugs)
viewtopic.php?f=1&t=52799&p=415959#p415959

Nov 2, 2015
Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)
viewtopic.php?f=1&t=52938

Nov 9, 2015
Impacts of Gut Bacteria (probiotics) on Immune Response to Tumors - anti-PD(L)1 Synergy but also taken alone.
viewtopic.php?f=1&t=53006&p=418204#p418204

Nov 17, 2015
The Currently Incurable Scientist: REPROGRAMMING A TUMOR FOR DEATH (RRx-001)
viewtopic.php?f=1&t=53072

Nov 24, 2015
RRx-001 Phase 2 Trial: New East Coast Site
viewtopic.php?f=1&t=53122&p=419630#p419630

Dec 6, 2015
Merck (anti-PD-1) + Amgen (anti-CSF1R) CRC Immunotherapy Trial Announcement
viewtopic.php?f=1&t=53218

Jan 12. 2016
BMS (major Opdivo & Yervoy immunotherapy company) announces their 2016 strategic plans, including MSS-CRC at the JP Morgan Healthcare company
viewtopic.php?f=1&t=53460

Jan 15, 2016
New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)
viewtopic.php?f=1&t=53472

Jan 22, 2016
Potential new biomarker to identify Stage 2 CRC patients who would benefit from chemotherapy
viewtopic.php?f=1&t=53523

Jan 25, 2016
New MSS CRC Phase 1 Trial: PF-06671008 (P-cadherin targeting)
viewtopic.php?f=1&t=53552

Jan 28, 2016
BBI-608 Clinical Trial Update
viewtopic.php?f=1&t=53576

Feb 4, 2016
Personalized Immunotherapy: Therapeutic Vaccines
viewtopic.php?f=1&t=53635

Feb 6, 2016
New MSS-CRC Immunotherapy Trial: JNJ-61610588 (anti-VISTA)
viewtopic.php?f=1&t=53643

Feb 10, 2016
MSS-CRC Immunotherapy Trial: AM0010
viewtopic.php?f=1&t=53677

Feb 15, 2016
For KRAS-Mutant CRC: PD-1 Combination Trial with cobimetinib (MEK inhibitor)
viewtopic.php?f=1&t=53710

Feb 26, 2016
DK's Personal Cancer Research Science Project
viewtopic.php?f=1&t=53792

March 19, 2016
New MSS Trial: anti-CSF1R "AMG 820" + anti-PD1
viewtopic.php?f=1&t=54065

March 19, 2016
MSS Trial: Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab)
viewtopic.php?f=1&t=54066

April 4, 2016
Crowdfunding a New CRC Trial at UCSD (Pulse High Dosed erlotinib)
viewtopic.php?f=1&t=54242

April 8, 2016
CCR2 Antag Clinical Immunotherapy Activity Against a "Cold" Tumor Type (Not CRC but Keep Reading!)
viewtopic.php?f=1&t=54282

April 15, 2016
AACR-2016 Clinical Trial Poster Abstracts: IMMU-130, CFI-400945, AM0010
viewtopic.php?f=1&t=54336

viewtopic.php?f=1&t=54337

viewtopic.php?f=1&t=54338

April 20, 2016
AACR-2016 Trial Data Release + 1st MSS-CRC Combo-Immunotherapy Trial Results Announcement for ASCO-2016
viewtopic.php?f=1&t=54391

May 2, 2016
New MSS-CRC Immunotherapy Trial - PDL1/CTLA4/FOLFOX - Liver-only Mets
viewtopic.php?f=1&t=54518

New MSS-CRC Immunotherapy Trial: TIL Trial at MD Anderson
viewtopic.php?f=1&t=54519

May 3, 2016
New MSS-CRC Immunotherapy Trial: Erbitux+Keytruda
viewtopic.php?f=1&t=54525

May 18, 2016
BIG (BIG!) MSS-CRC Immunotherapy News Out of ASCO! (MEKi + PDL1i)
viewtopic.php?f=1&t=54674

May 20, 2016
French MSS-CRC Trial (PDL1 + anti-CSF1R)
viewtopic.php?f=1&t=54684

May 24, 2016
MDA Personalized Therapeutic Vaccine Now Recruiting
viewtopic.php?f=1&t=54713

May 31, 2016
New MSS-Elegible PDL1 Combo Trial (RO6895882, CEA-targetted IL2)
viewtopic.php?f=1&t=54774

June 2, 2016
READ! PHASE 3 MSS-CRC Immunotherapy Trial Just Registered!! (Cobi + Atezo)
viewtopic.php?f=1&t=54792

June 5, 2016
Today's ASCO-2016 Oral Presentation on MSS-CRC PDL1-MEK Immunotherapy Success
viewtopic.php?f=1&t=54825

June 5, 2016
ASCO-2016: Updated PD1 vs PD1-CTLA4 Immunotherapy for MSI-high CRC
viewtopic.php?f=1&t=54816

June 11, 2016
Global Randomized Phase 3 Clinical Trial for BRAF-mut CRC
viewtopic.php?f=1&t=54874

June 15, 2016
Phase 2 Clinical Trial: BAX69 + either 5-FU or Panitumumab SoC
viewtopic.php?f=1&t=54924

June 15, 2016
BRAF-Mutant Small Bowel Cancer (or other rare cancers)
viewtopic.php?f=1&t=54925

June 15, 2016
New RRx-001 Non-Randomized Trial (Northern CA & NJ)
viewtopic.php?f=1&t=54933

June 24, 2016
Interview with Clinical Trial Principal Investigator of MSS-CRC MEK-PDL1 Immunotherapy Breakthrough
viewtopic.php?f=1&t=55021&p=436044#p436044

August 3, 2016
MSS-CRC: New Oncolytic Virus + PD1 Inhibitor Trial
viewtopic.php?f=1&t=55358

August 7, 2016
Combination of radiotherapy (radiation) with PD1 immunotherapy in MSS-CRC
viewtopic.php?f=1&t=55393

August 19, 2016
New MSS-CRC PD1 Immunotherapy Trial in MINNESOTA
viewtopic.php?f=1&t=55522

August 19, 2016
Cleveland Clinic: New CRC Targeted Therapy Trial
viewtopic.php?f=1&t=55523

September 2, 2016
Immunotherapy Trial: Patients WITH Brain Metastases
viewtopic.php?f=1&t=55812

September 18,2016
New MSS-CRC Immunotherapy Trial: Arginase Inhibitor CB-1158
viewtopic.php?f=1&t=55940

September 23, 2016
Big Trial Announcement: MSS-CRC/KRAS-Mut TCR Cellular Immunotherapy Trial from Kite Pharma
viewtopic.php?f=1&t=55999

September 26, 2016
***My personal project***
STAT NEWS: A CANCER RESEARCHER RACES TO FIND A [MSS-CRC] CURE — FOR HIS OWN INCURABLE CANCER
viewtopic.php?f=1&t=56022

September 27, 2016
MSS-CRC: PD1/NKTR-214 Combo Trial Announcement
viewtopic.php?f=1&t=56031

September 29, 2016
Fasting and Chemo: My Take on It
viewtopic.php?f=1&t=56049

October 1, 2016
Citizen Science: Reporting of FASTING and Chemo Results
viewtopic.php?f=1&t=56080

October 16, 2016
***My Personal Trial***
DK37's FIRST MSS-CRC IMMUNOTHERAPY CLINICAL TRIAL (ONCOLYTIC VIRUS + PD1)
viewtopic.php?f=1&t=56213

November 4, 2016
Big New MSS-CRC Immmunotherapy Trial: anti-CD47
viewtopic.php?f=1&t=56383

November 19, 2016
Peri Mets / MSS-CRC Immunotherapy Trial (Oncolytic Virus + anti-PDL1)
viewtopic.php?f=1&t=56499

November 20, 2016
A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc
viewtopic.php?f=1&t=56503

December 7, 2016
MSS-CRC Trial: Phase 2 Study of GVAX (With CY) and Pembrolizumab in MMR-p Advanced Colorectal Cancer
viewtopic.php?f=1&t=56606

December 7, 2016
MSS-CRC Immunotherapy Trial: CEA-CD3 Bifunctional + PDL1 Inhibitor
viewtopic.php?f=1&t=56607

January 4, 2017
DK37's Personal BIG PICTURE Opinions on CLINICAL TRIALS
viewtopic.php?f=1&t=56838

July 6, 2017
My personal choice for best ASCO-2017 MSS CRC Clinical Trial and Presentation
viewtopic.php?f=1&t=58347
Last edited by DK37 on Thu Jul 06, 2017 3:38 pm, edited 57 times in total.
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

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DK37
Posts: 510
Joined: Tue Sep 17, 2013 8:31 am
Location: San Diego

Re: DK37 Science Posts List

Postby DK37 » Sat Jan 30, 2016 10:27 pm


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CRguy
Posts: 10472
Joined: Sun Feb 10, 2008 6:00 pm

Re: DK37 Science Posts List

Postby CRguy » Thu Oct 19, 2017 4:50 pm


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

Re: DK37 Science Posts List

Postby GrouseMan » Tue Nov 27, 2018 1:54 pm

OK since DK (Tom) has passed and we all miss him. And I see that few science posts have been made in a while - I thought I would post a link to something I read this morning concerning a Mushroom extract used in Taiwan that had been used to treat several conditions in folk medicine including bowel cancer. Being a former Drug Discovery chemist doing anticancer research, I have often had occasion to examine plant derived compounds as potential anti-cancer drugs. Typically we isolate the active ingredients and test them look for the one with the most activity and then modify it to make it a better drug candidate.

The paper I am linking to create a extract from the Antrodia cinnamomea mushroom that only grows on a particular type of tree in Asia. They found that a particular isolated fraction containing several natural product carboxylic acids seem to be quite active against many colon cancer cell lines we use in research - they tested about 6 of them and the extract was active against all of them to some degree or other. That is pretty good as some of these are resistant to some other chemotherapy agents. On very close examination using methods that are over even my head not being a molecular biologist they determined that this extract worked on the CHOP/TRB3/Akt/mTOR signaling pathway in colorectal cancer cells. They showed this to be the case in isolated tumor cells as well as in mouse xenographs and in a dose response manner. BTW this was all via direct exposure of the tumor cells to the extracts in a dish or via injection into the blood stream in the mouse.

Of course this is all very early and basic work. There have been many studies of these sorts of extracts from this mushroom showing activity against a couple of different cancers but until now no one knew what the mechanism of action was. So - it may one day provide another natural product derived anti-cancer drug now that they have some idea how the extract works and what the major components of the extract are.

Here is a link to the paper - Antrodia cinnamomea induces autophagic cell death via the CHOP/TRB3/Akt/mTOR pathway in colorectal cancer cells: https://www.nature.com/articles/s41598-018-35780-y

Its rather technical but I found it an interesting read.

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

cartech78
Posts: 78
Joined: Thu Oct 25, 2018 6:22 pm

Re: DK37 Science Posts List

Postby cartech78 » Tue Nov 27, 2018 6:29 pm

Did i read the study right that it could work good with 5fu? Couldn’t make out if they were saying it was good with 5fu or diminished 5fu efficacy. Im on 2g of curcumin, 3g of micronized resveratrol, and low dose aspirin currently With my Folfox regimen. Interested in trying this if it plays well with Folfox.
40 Y/o male
Dx 10/5/18 stage lV CRC
Sg colon
23 inoperable liver mets largest 4.5 cm
Colon resection 10/6/18 clean margins
Starting FolFox on 11/18
2nd opinion at MSK on 12/18
HAI pump installed on 3/6/2019 also found 20 more small tumors on liver scans missed
7/2/2019 MRI and CT show only 2 liver tumors visible and they are shrunk by 3/4
11/25/19- Liver resection at MSK- got out all cancer and am NED. More scans and mop up chemo to follow.
1 month Scan clear! Jun/20 scans still clear. Off chemo since 3/20

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

Re: DK37 Science Posts List

Postby GrouseMan » Wed Nov 28, 2018 12:40 am

cartech78 wrote:Did i read the study right that it could work good with 5fu? Couldn’t make out if they were saying it was good with 5fu or diminished 5fu efficacy. Im on 2g of curcumin, 3g of micronized resveratrol, and low dose aspirin currently With my Folfox regimen. Interested in trying this if it plays well with Folfox.


It was used as a control to compare gene expression following treatment with 5-FU to that with treatment using the ACF2 extract. They were not used together in this paper. I suspect that they might be synergetic but that experiment would have to be done. Also note - even if you can find this extract used in this paper it would have to be prepared fresh, as I suspect it would degrade rather quickly being a mixture of very polar molecules. On going back and reading the actual Mouse experimental details it appears they give the extract orally once daily at 100, 200, and 400 mg/kg body weight. This surprises me as I would expect that the complex polar compounds found in the extract (a lot of complex carboxylic acids) would not survive oral administration and be sufficiently systemically bioavailable. If you weigh about 80 Kg you would have to take 32 grams of this per day at the highest dose. Something like 2.2 tablespoons of this extract per day. That's probably not going to go over very well in your GI track.

I think a lot more work needs to be done with these things, but it is still interesting now that they have a much better idea of their mechanism of action. Its still quite a mixture of chemicals and it might still be hard to determine which ones provide this profile or if its several acting on different parts of the signaling pathway at this point.

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

cartech78
Posts: 78
Joined: Thu Oct 25, 2018 6:22 pm

Re: DK37 Science Posts List

Postby cartech78 » Wed Nov 28, 2018 1:25 am

Thanks for the reply! Yeah you’re right that is a shit ton of that stuff to take. Maybe if they can synthesize the stuff and mix it with pepper extract like curcumin it would be better absorbed. That science is miles and miles over my head. I wish we could get more money to go to research of these types of things. Im fairly certain there is something out there that can be taken with Standard Chemo to put it in overdrive. In the meantime I will keep popping supplements with just enough info to be dangerous :P
40 Y/o male
Dx 10/5/18 stage lV CRC
Sg colon
23 inoperable liver mets largest 4.5 cm
Colon resection 10/6/18 clean margins
Starting FolFox on 11/18
2nd opinion at MSK on 12/18
HAI pump installed on 3/6/2019 also found 20 more small tumors on liver scans missed
7/2/2019 MRI and CT show only 2 liver tumors visible and they are shrunk by 3/4
11/25/19- Liver resection at MSK- got out all cancer and am NED. More scans and mop up chemo to follow.
1 month Scan clear! Jun/20 scans still clear. Off chemo since 3/20

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CRguy
Posts: 10472
Joined: Sun Feb 10, 2008 6:00 pm

Re: DK37 Science Posts List

Postby CRguy » Thu Nov 29, 2018 6:50 pm

GrouseMan wrote:OK since DK (Tom) has passed and we all miss him...
And I see that few science posts have been made in a while - I thought I would post a link to something I read this morning ...

GrouseMan

Thanks GrouseMan
you are a valued member of this family and any input here, especially science / tech based is much appreciated !

Yes ... we do all miss Tom, and since Maia has also been MIA lately :(
I admit we could use some more input in this topic.

Cheers and Best wishes
CRguy
Caregiver x 4
Stage IV A rectal cancer/lung met
17 Year survivor
my life is an ongoing totally randomized UNcontrolled experiment with N=1 !
Review of my Journey so far

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

Re: DK37 Science Posts List

Postby GrouseMan » Thu Jan 24, 2019 12:00 pm

OK - I know plenty of you have an interest in MSI, MSS and TMB with regards to Immunotherapy agent usage. There have been a number of studies publish in the last year or so, but I have found the following ones to be quite interesting, and I am hopeful that before long more people will have their tumors profiled for TMB (Tumor Mutation Burden). The first paper is the following:

https://www.nature.com/articles/s41588-018-0312-8

Unfortunately I don't have a subscription to this journal so I can't access the paper at this time directly. Perhaps if I make a trip to the university I can get a copy of the paper. However - The following link I feel does a very good job of reporting the results of the above paper very well.

https://www.ajmc.com/newsroom/tumor-mut ... unotherapy

In these paper they point out different solid tumor types have different TMB cutoff levels where Immunotherapy drugs have a significant benefit. For Colon Cancer they indicate a TMB of about 52. But I suspect there are exceptions where lower than this immunotherapy is still useful. The following paper is also quite interesting.

https://bmcimmunol.biomedcentral.com/ar ... 018-0285-5

It is quite detailed. Note all these papers I presented so far concern overall TMB for multiple tumor types. Thing is most of the data so far has been for Melanoma and NSCLC where these immunotherapy drugs have been approved the longest and the vast majority of patients have come from. So its probably a bit biased towards the TMB numbers associated with these tumor types.

Here is a citation just concerned with Colon Cancer MSI, MSS and TMB

https://europepmc.org/abstract/med/30638897

Again I am sorry I don't have access to the last one directly either, but hopefully can get to a major research library sometime soon to read it. These are all very recent research publications. (Jan 2019) Hope everyone considering use of one of the immunotherapy drugs has a look, and armed with this new data perhaps can talk their oncologist into doing appropriate testing and consider these new treatments.

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

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

Re: DK37 Science Posts List

Postby GrouseMan » Thu Sep 12, 2019 2:03 pm

OK - Its been a while since I posed anything scientifically interesting. But I saw an publication in Science Translational Medicine ( 11 Sep 2019: Vol. 11, Issue 509 ) which I found very compelling. Title:

Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.

Seems some mechanisms of action for clinical candidates might be in error or have more to do with other cytotoxic effects than the proposed mechanism that brought them to the clinic in the first place. First off I'll provide a link to the original work. I read about this first and pondered it for a while as to if I should post about it.

https://stm.sciencemag.org/content/11/509/eaaw8412

Now this is very technical and I hardly understand the full methodology they used in this myself. I am not a Biologist (instead a drug discovery chemist) and don't understand completely how these methods work. Needless to say drug discovery chemists believe we are targeting the correct mechanism when we are working on doing drug discovery. Generally - in this work they are setting up common cancer cell lines NOT to produce the target proteins that the clinical candidate drugs are supposedly the substrate for. I was worried about trying to summarize this for everyone such that it would be accessible to some of you. But then another forum I read called In The Pipeline had a discussion about this paper today. Its link is here. Derek does a better job summarizing it than I could.

https://blogs.sciencemag.org/pipeline/a ... ot-be-real

This has some interesting implications to me. We often talk about doing genetic testing to see what mutations tumors have so the Oncologist can tailor treatment. Select inhibitors (Drugs) based on cancer mutations these drugs might target. As indicated in the original publication, some targets might actually be misidentified. This could be why often directed therapy hasn't been as successful as we believed it should have been. Could be the target of the drug isn't what we think it is? Hopefully this get more wide spread consideration and further research perhaps into existing drugs targeting tumors.

I added the following later in the day 9/12/2019:

it seems there is some commentary I saw later today from the latest issue of Science Magazine.

https://science.sciencemag.org/content/ ... id=2985387

I hope this gives you all something to think about.

Good Luck

GrouseMan
Last edited by GrouseMan on Fri Sep 13, 2019 12:07 am, edited 1 time in total.
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

User avatar
CRguy
Posts: 10472
Joined: Sun Feb 10, 2008 6:00 pm

Re: DK37 Science Posts List

Postby CRguy » Thu Sep 12, 2019 6:16 pm

Thanks GrouseMan, very interesting indeed.

I can't say I have digested all the info yet BUTT I think the more we learn,
the more we know we NEED to learn, and this would seem to be a case in point.

Whether the discoveries come from inspiration, desperation, exasperation or good old perspiration !!!!
Good science WILL always lead us to where we need to be.

Harmony
CRguy
Caregiver x 4
Stage IV A rectal cancer/lung met
17 Year survivor
my life is an ongoing totally randomized UNcontrolled experiment with N=1 !
Review of my Journey so far

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

Re: DK37 Science Posts List

Postby GrouseMan » Fri Oct 04, 2019 12:16 pm

Here is something interesting I came across today. It concerns supplemental Anti-oxidants and NAC (N-Acetyl Cysteine) in particular. Have a look at the following post in The Pipeline by Derek Lowe.

https://blogs.sciencemag.org/pipeline/a ... rning-shot

Implications here as I see it is that the use of Anti-Oxidants as we age - permits formation of cancers because cells under oxidative stress as we age don't die as they should and instead under anti-oxidant supplementation live to form cancerous cells. So trying to prevent oxidation is not helping as we get older but likely stabilizing damaged cells that we want to die.

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

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

Re: DK37 Science Posts List

Postby GrouseMan » Wed Feb 26, 2020 3:14 pm

OK - Here is a new post on Vitamin C. We have in the past had members of this forum try High dose IV Vitamin C infusions to treat their cancers. Its been long held that this has anti-cancer properties, but so far not enough evidence, and certainly - I doubt it has done little more that stem the tide a little with members of this forum that tried it and passed. Well seems it just might have some effect when used along with Immunotherapy treatment.

High-dose vitamin C enhances cancer immunotherapy: Science Translational Medicine 26 Feb 2020: Vol. 12, Issue 532, eaay8707
See: https://stm.sciencemag.org/content/12/5 ... id=3222322

Seems bottom line is, Combination of Vitamin C and Immune Checkpoint Therapy can be curative in models of mismatch repair–deficient tumors with high mutational burden. This work provides a rationale for clinical trials combining Immune Checkpoint Therapy with high doses of Vitamin C. This work was done in a mouse model and includes colon cancer tumor types.

This looks promising and hopefully someone will attempt a clinical trial using high dose Vitamin C, in connection with an Immune Checkpoint Therapy such a PL-1 etc. I was always skeptical of Vitamin C therapy as its been extensively studied but never has panned out in the clinic. Maybe this will help some with MSI High mutational burdened patients.

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

User avatar
CRguy
Posts: 10472
Joined: Sun Feb 10, 2008 6:00 pm

Re: DK37 Science Posts List

Postby CRguy » Sat Feb 29, 2020 9:06 pm

Thanks for that updated info GrouseMan

I was always skeptical of Vitamin C therapy as its been extensively studied but never has panned out in the clinic.
Maybe this will help some with MSI High mutational burdened patients.


That would be most welcome !!!!

Cheers
CRguy
Caregiver x 4
Stage IV A rectal cancer/lung met
17 Year survivor
my life is an ongoing totally randomized UNcontrolled experiment with N=1 !
Review of my Journey so far

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

Re: DK37 Science Posts List

Postby GrouseMan » Mon Mar 02, 2020 10:46 am

Follow up about Vitamin C. I recommend a quick read of the following which gives some perspective and is bound to result in some discussion on Derek's Blog Forums. This is from In the Pipeline by Derek Lowe a Medicinal Chemist who is a well known blogger, of Chemistry and Drug Discovery:

https://blogs.sciencemag.org/pipeline/a ... o-oncology

In this he discusses this latest research from the Italian team on Vitamin C I posted on previously with work done by Linus Pauling a two time Nobel Prize winning chemist. Being a chemist myself I greatly admired Professor Pauling but still took his thoughts and research on Vitamin C with a grain of salt!

Enjoy,

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


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