21st Century Cancer Therapies  

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Jcancom
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30/10/2018 4:18 pm  

There are a range of extremely impressive next generation cancer therapies that I have encountered lately and I think that it would be valuable to have a thread devoted to listing and discussing them. By "21st Century Cancer Therapies" I intend to specifically focus on a new wave of technology that has up till this point been entirely unavailable to us.

Most of our discussions on this forum have stressed currently available chemicals and treatments. It is of course wise to focus on this aspect of treatment that is within the easy reach of patients. However, many of these newer treatments are not that far beyond our reach and they offer substantially more effective and safer potential therapy.

To start off this thread I will mention tumor targeting peptides. At the start of this year a new formulation of 3-BP was reported PMID:29286239. I did not examine it closely because I had assumed it was simply another generic liposomal formulation. It was not. This liposomal formulation used a tumor targeting peptide to bring the 3-BP to the tumor. More specifically, this formulation, used the tumor targeting peptide CREKA to attract the liposomes to the tumor vasculature. 

The in vivo part of the research found no side effects of the treatment, while demonstrating significant anti-tumor effects. In fact, the research presented does not appear to maximize the effectiveness of this approach as previous research used a next generation of this technology to obtain even better results. For example, the more advanced research also included tumor cell targeting  in addition to the tumor vasculature targeting peptide, had a more sophisticated peptide sequence, used decoy liposomes, possibly used clondroate to knock down unwanted liver activity etc.. 

This tumor targeting approach appears to be a highly powerful anti-cancer platform. One could well imagine  a variety of ways to make it even better. For example, one could load up these liposomes with 3-BP and paracetamol, paracetamol alone, include oncolytic viruses, 3-BrOP, MG, circumin and many others. This is very impressive! The cancer drugs would be targeted directly to the tumor. One could use much lower doses and achieve much better results.

Another upgrade might be to find a way to reduce the small amount of systemic exposure by perhaps adding a treatment that would knock down the residual liposomes after about 2 hours that had not accumulated in the tumor (See Figure 4A from the reference above).    

What is even more encouraging is that the method to make these nanoparticles appears to be best described as basic (actually very basic). Making these nanoparticles would result in a truly impressive 21st Century Cancer Therapy.

After learning the basic method one would then have opened a range of other potential treatment options. For example, using an almost identical process, another tumor targeting therapy using the same peptide added in an anti-platelet drug (instead of 3-BP). With this particular nanoparticle, metastasis was almost eliminated!  PMID:28435448

One could easily imagine a treatment strategy which included tumor targeting liposomes were used to attack the primary tumors, while at the same time other tumor targeting liposomes were used to prevent any additional metastatic spread.

There are many other instances of other therapies within this same platform. The liposomes could contain almost any cancer drug which could create nearly unlimited potential. 

 

 

 

 

 

 


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Daniel
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31/10/2018 10:50 am  

Hi J, not liposomes but speaking about targeted drugs and 21st Century, here is a small biotech company with a drug in phase 3 and very good results  http://www.sesenbio.com/vicinium.php


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Jcancom
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02/11/2018 2:57 am  

Good one D!

Here is another one that is a real eye opener! X-Ray PDT!   

https://www.ncbi.nlm.nih.gov/pubmed/30195803  

I posted about this technology about a year ago on the compass thread, though it keeps on getting better. The latest version is giving very extreme ROS generation using a nanoparticle coupled to Rose Bengal. There are still problems with toxicity and with the dosing (the current study is using intratumoral which defeats most of the purpose of an X-Ray approach), however this latest research is a big step forward. If they could load up the nanoparticles perhaps in chitosan and then give targeted X-Rays, you could have a treatment that might reach nearly anywhere in the body and deliver very impressive results. This would not be an expensive treatment. All it needs is the nanoparticles and low dose X-rays.


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dumbcritic
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03/11/2018 12:13 am  

Provectus Bio are running trials of PV-10 (ten percent solution of rose bengal disodium)  https://www.provectusbio.com/publications


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dumbcritic
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Jcancom
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07/11/2018 5:59 pm  

I have been posting about E260 recently on the compass thread. I believe that critic first alerted us to this one. This is a very startling treatment. It is a highly specific, highly safe (in mice), highly effective OXPHOS inhibitor. Probably the biggest insight that we have all gained after all of these years is that combining specific OXPHOS and glycolysis inhibitors can result in very large anti-cancer effects. This is what this article found. Somewhat surprisingly even when they used E260 as monotherapy, the tumor still had exponential growth. Yet by merely adding in caloric restriction (glycolytic stress), the tumor completely stopped growing in vivo.

https://www.nature.com/articles/s41467-017-00832-w#Sec61

This chemical is already appearing online from the chemical suppliers for research purposes. This could be what we have been waiting for. There still could be resistance etc., though at least for the first time that I am aware of we will have a clear test and demonstration of 21st Century metabolic cancer treatment. A phase 1 clinical trial is expected to start in April. I will be interested to see whether the patients realize that taking E260 by itself likely will have no therapeutic effect, though combining it with calorie restriction, and many others could have a very large effect.  


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Jcancom
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13/11/2018 2:51 am  

21st Century TMZ?  It is quite impressive that chemists could take something such as TMZ, tweak it and make it apprarently much more effective.

https://pubs.acs.org/doi/pdf/10.1021/acschembio.8b00864


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dumbcritic
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13/11/2018 8:12 pm  

Has any more info about the PhI trial of E260 been disclosed?

 

Here is a webcast from Nektar and it includes NKTR-262 data starting at 19 mins  https://edge.media-server.com/m6/p/mjtntqda

 

Aduro also hosted another one at SITC  https://edge.media-server.com/m6/p/7uebohba


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Jcancom
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20/11/2018 3:36 pm  

critic, I am also anxious to hear more about E260, though it does seem quite silent out there. I can see no reasonable objection to this moving ahead into clinical trials. This is very exciting! Removing OXPHOS selectively from cancer is an enormous step forward!.

This one might also move things forward. I have been wondering for a while what might happen if it were possible to combine a mito drug with chitosan. The idea would be that you might have the selectivity of targeting to the tumor's acidic environment while at the same time having the power of mito to move drugs to the mitochondria. The below url suggests that this might even been doable. 

This would be great! With mito drugs you have at least some selectivity to cancer based on the charge difference between cancer and normal cells, though increasing this selectivity could help amplify the benefits and reduce risk.

https://www.ncbi.nlm.nih.gov/pubmed/29642447


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Jcancom
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20/11/2018 6:24 pm  

This one seems to be more a cancer treatment from the 21st BC, though surprisingly it seems to work! My interest with glycerol was peaked, when I looked at its metabolism into glycolysis. What I found interesting was that glycerol avoids HKII! Sidestepping HKII seems like a good plan as it is attached to VDAC and is grabbing ATP that other HKs could use in glycolysis. The metabolic pathway that glycerol uses requires 1 fewer ATP (bad news), though also appears to take an extra NAD! My interpretation of this is that perhaps one could upset the NAD/NADH balance of cancer cells by using up more NAD.  Glycolysis might become interrupted because of this. NADH also is worth 3 ATP in OXPHOS. If one were to shut off OXPHOS then this NADH would have little value.

https://chestofbooks.com/health/disease/cancer/Emanuel-Revici-Research-Physiopathology/Butanol-Glycerol-Cancer-Treatment-Continued.html


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Jcancom
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06/01/2019 4:23 am  

Very impressive! Through VDAC1 they were able to "normalize" cancer cells!

https://www.mdpi.com/2072-6694/10/12/499/htm


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Jcancom
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06/01/2019 4:26 am  

This one also is impressive and flew below radar. They have created a new formulation of 3-BP!

https://www.omicsonline.org/conference-proceedings/cellular-therapies-pain-medicine-2018-tracks.digital/#10

Total mystery what the combo with IKK-2 is all about.

https://www.selleckchem.com/products/sc-514.html

 


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