New Shay lab paper

[cheng_ho]

http://genomemedicine.biomedcentral.com ... 016-0324-x

[biopearl]

Thanks Cheng, nice article. Some of table 2 studies indicate "results not available in public domaine". I interpret this to mean no positive effect. I think a positive study would require release of information to stockholders as a material event and its just not there for the studies noted with the outstanding exception of hematologic diseases (but not lymphocytic lines). Have enjoyed your contributions. Having the Dartmouth library close is a nice perk. Regards, bp

[Fishermangents]

Great article. Thanks, Cheng. Next to the high tech content there is a nice overview on clinical experiences with imetelstat:

"Imetelstat has been extensively evaluated for its activity and efficacy against multiple cancer cell lines and in mouse xenograft models in preclinical studies. Imetelstat demonstrated potent inhibitory action against telomerase, causing shortening of telomeres in a large spectrum of cancer cell lines derived from tumors of the bladder, breast, lung, liver, prostrate and pancreas [62–64]. In vivo preclinical studies in mouse models of human tumor xenografts showed that the compound was well tolerated and highly efficacious in inducing telomerase inhibition, leading to reduced tumor growth, prevention of metastasis, and sensitization of tumors to standard chemotherapy [65]. Imetelstat was also found to efficiently prevent glioblastoma tumor growth in a xenograft model by crossing the blood–brain barrier, probably owing to its highly lipophilic nature [66]. Additionally, simultaneous suppression of homologous recombination and telomerase activity in a mouse model of Barrett’s adenocarcinoma with the combination of nilotinib (tyrosine kinase inhibitor) and imetelstat was reported to be more effective compared to either compound alone [67]."

Also interestig is fig.3, first row:
"GRNVAC1 was found to be safe and well tolerated. Positive immune responses in 55 % of patients. ../.. Clinical trial results have demonstrated that GRNVAC1, Vx001 and GV1001 are promising telomerase-targeting vaccines capable of stimulating CD4+ and CD8+ responses in telomerase-positive tumors, showing minimal effects on normal cells and no autoimmunity."
GRNVAC1 is licensed by Geron to Asterias.

This puzzles me a bit:
"Telomere shortening requires a series of cell division cycles to become apparent, and treatment may have to be given continuously for months to induce therapeutically relevant tumor reduction effects."
At the same time it is reported that imetelstat generates rapid responses. How does that correspond?

[Fishermangents]

Bio, I think there can be more explanations for not making the results public. You're probably right in thinking that the results were not spectaculary positive. But they also don't need to be negative either. There can be various reasons for not publicizing. It can be that they don't exaclty know the nature of the data. Or they don't publicize for competitive reasons. It can also be that they see non-imetelstat related reasons for meager responses. It can also be that there were simply not enough data for making a public statement.

[cheng_ho]

Good point, Fisher, imet often shows an effect long before it "should"... somehow interfering with telomerase, interferes with cell division long before the telomeres shorten. If we understood exactly how we might just use that effect and forget the telomere shortening entirely