for data behind the Abstract google sorafenib imetelstat and select Doanload Appendix
7 Cancer types tested p value less than 0001
Over 90% of cancer cells express telomerase, which is required for their survival. However, telomerase inhibitors alone have so far failed to provide any significant clinical benefit. Therefore, identifying and targeting genes that can enhance the effects of telomerase inhibitors will greatly benefit a large population of cancer patients. We find that simultaneous inhibition of p21 and telomerase synergistically suppresses tumor growth. We also show that our approach is useful for treating p53 mutant cancers, when used with therapies that restore the function of mutant p53. We anticipate that simultaneous targeting of p21 and telomerase will overcome the current limitation of single-agent telomerase therapeutics and provide an effective method to treat cancers that rely on telomerase activity for survival.
Tumor suppressor p53 plays an important role in mediating growth inhibition upon telomere dysfunction. Here, we show that loss of the p53 target gene cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21WAF1/CIP1) increases apoptosis induction following telomerase inhibition in a variety of cancer cell lines and mouse xenografts. This effect is highly specific to p21, as loss of other checkpoint proteins and CDK inhibitors did not affect apoptosis. In telomerase, inhibited cell loss of p21 leads to E2F1- and p53-mediated transcriptional activation of p53-upregulated modulator of apoptosis, resulting in increased apoptosis. Combined genetic or pharmacological inhibition of telomerase and p21 synergistically suppresses tumor growth. Furthermore, we demonstrate that simultaneous inhibition of telomerase and p21 also suppresses growth of tumors containing mutant p53 following pharmacological restoration of p53 activity. Collectively, our results establish that inactivation of p21 leads to increased apoptosis upon telomerase inhibition and thus identify a genetic vulnerability that can be exploited to treat many human cancers containing either wild-type or mutant p53.
Five hours ago, for our reading pleasure... Amgen Inc. (AMGN) announced that AMG 416 has met the primary as well as secondary endpoints in the second phase III registration study evaluating the candidate for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (:CKD), receiving hemodialysis. We expect investors to react positively to the news.
Sentiment: Strong Buy
Report out for Dan Loeb's fund, opened new position Q3 in AMGN. Could be getting ready to get "active" with the board here.
I think its time Amgen/Onyx ann this. http://www.patrys.net.au/images/stories/mediareleases/PABReleaseOnyxpartnership.pdf
Patrys to initiate an Investigator-Sponsored
Clinical Trial using PAT-SM6 in combination
with Onyx Pharmaceuticals’ carfilzomib
Combination study with Patrys’ PAT-SM6 and Onyx Pharmaceuticals’ carfilzomib
Trial to be conducted at the University of Würzburg, Germany under the leadership of
Professor Dr. Hermann Einsele, a world-acclaimed expert in blood cancers
Melbourne, Australia; 11 November, 2013: Patrys Limited (ASX: PAB), a clinical stage biotechnology
company has today announced that it is initiating an investigator-sponsored trial (IST) evaluating the
effectiveness of Patrys’ lead anti-cancer drug PAT-SM6 in combination with carfilzomib, in patients
with relapsed and refractory multiple myeloma (MM). The trial will be headed by Professor Dr.
Hermann Einsele, Director of the Department of Medicine II, University of Würzburg, Germany, and
is being funded by Onyx Pharmaceuticals, Inc., an Amgen subsidiary.
Both clinical and preclinical studies of PAT-SM6 conducted to date have shown evidence of activity in
patients with relapsed and refractory MM. One of the notable features of PAT-SM6, being
demonstrated in the currently-ongoing Phase I/IIa clinical trial, is the lack of serious side-effects in
treated patients. This feature of PAT-SM6 may allow it to be safely administered in combination with
carfilzomib and may have the potential to improve current treatments for MM. Carfilzomib is a
proteasome inhibitor owned by Onyx, and is marketed in the United States (U.S.) under the brand
name Kyprolis® (carfilzomib) for Injection. Onyx will provide carfilzomib study drug for the trial.
Selling because of the results of FOCUS makes no sense to me because it was a poorly designed study. The trial compares two active arms in heavily pretreated patients in which Kyprolis was used at the standard dose, which no one believes is the optimal dose of the drug. The control arm was a steroid with the option of a Dr. adding cyclophosphamide if he/she wanted to (and almost all did) - Why was there not a third arm that combined steroid/cyclo + Kyprolis? The way this study was designed is the major reason for its failure, not the drug.
EU approval will go forward with the better designed ASPIRE data set.
oro I sayit yo have two bubbles. One in yo head and one in yo back side. which one is going to burst first? I aint got no idea but yo not very smart and could be a dummy short .
Sentiment: Strong Buy
So people who took the original pumper's advice, enjoying a 7% loss in ARIA and missing a 5% increase in AMGN are geniuses like you then?
Makes me wonder if the cutbacks are somehow connected to the anticipation of this announcement. Overall, AMGN has been a big disappointment as an investment for the past 14 years. It's up but not by as much as the S&P 500 Index over the same period of time. From 2000 to 2012, it just bounced back and forth between about $40 and $80 and went nowhere fast. Looks like we could be in for more of the same. AMGN might be a good trading stock, but it sucks for long-term investors.