Quote:
slcimmuno Member Level Friday, 05/26/17 09:11:50 AM
Re: cabel post# 183360
Post # of 183404

Good find - def looking fwd to seeing more of Kevetrin in action, doing its P53 thing ... hopefully when orally formulated (sounds promising) keeping cancer away by popping a few K pills a day

The article you sent got me Googling ... another recent interesting P53 read

//

"Injecting activator of a powerful tumor suppressor directly into the cancer increases tumor destruction, decreases toxicity"

Nutlin-3a, which Cui used in the studies in models of lymphoma and melanoma, works to activate more of the normal p53 by suppressing a natural p53 inhibitor that is overexpressed in many tumors.

But early experience in clinical trials have been disappointing, Cui said. Also, given systemically, as many cancer therapies currently are, it can have toxic results like suppressing the bone marrow so patients can become anemic or worse as well as killing potentially helpful immune cells. "There is no selection," Cui said, of impacted cells.

With the study, the scientists instead injected nutlin-3a directly into the tumor. They watched as p53 was activated and immune cells began moving into the area. They also watched the immune cells, now educated on what to attack, move out of the primary tumor site to other areas in the body where tumor cells had traveled. Tumor spread, or metastasis, is a primary reason cancer is lethal.

[...]

Next steps include adding to their mix drugs that can restore normal p53 in tumors with already altered versions, a move they hope will further broaden the future therapeutic potential of their approach.

https://www.sciencedaily.com/releases/2017/05...083348.htm

Gang Guo, Miao Yu, Wei Xiao, Esteban Celis, Yan Cui. Local Activation of p53 in the Tumor Microenvironment Overcomes Immune Suppression and Enhances Antitumor Immunity. Cancer Research, 2017; 77 (9): 2292 DOI: 10.1158/0008-5472.CAN-16-2832

and:

Quote:
slcimmuno Member Level Friday, 05/26/17 11:28:52 AM
Re: KMBJN post# 183369
Post # of 183404

Glad to see u back too KMBJN - your analyses many pay grades above mine Is very interesting to read about these p53 combo-type approaches. Targeting the once-considered "undruggable"... seems we're getting closer and closer.

http://tatcongress.org/wp-content/uploads/201...hwartz.pdf

I recall this is where Aprea (APR-246 / PRIMA-1 MET) is headed as it seems their compound has some toxicity concerns (unlike Kevetrin) as a Monotherapy (like Nutlins) -- below articles, Wiman Group.

Also saw long dormant Aileron posted an abstract at ASCO. Their stapled-peptide approach.

http://www.businesswire.com/news/home/2017051...-ALRN-6924

APREA
https://academic.oup.com/biohorizons/article/...tant-p53-a

"PRIMA-1 acts to restore the mutant p53 by modifying thiol groups in the core domains of the protein. Its success is well documented, with many studies in different cancer models proving its effectiveness. This, however, is not unanimous, with some questions being raised about its efficacy and other aspects such as possible resistance mechanisms as well as potentially harmful degradation products."

https://www.researchgate.net/profile/Vladimir...e34a18.pdf

http://ki.se/en/onkpat/klas-g-wimans-group

http://tatcongress.org/wp-content/uploads/201...-Green.pdf