Success is in steps. Each step forward is progress while each step backwards provides opportunity to two fold the next step forward.
Kevetrin has only been taking steps forward so far. Certainly not without competition. If Cellceutix were the only company in the world working on cancer research, well then, cancer would be relatively unknown to mankind wouldn't it? Many companies have been working to reactivate P53 though that isn't the end game but seemingly a very optimistic goal. See page 14 of Cellceutix's Cancer Report https://static1.squarespace.com/static/571535...e+Vers.pdf
This shows Roch, Daichii Sankyo, Oprea failures. There are many others striving for the same goal including private companies. Interesting how even the private ones aren't as private as they seem if you have the money to invest with them, or maybe just know how to do the right DD to find them. Millions are poured into this research. Close to $40M placed into another one just this January.
So how is Cellceutix succeeding? Kevetrin, thus far has been shown to reactivate P53.
Lets see how the ovarian trial goes.
Just the basics are posted on the clinical trial site since we know so much more can be gained by the study...
I think what may be flagged by some is how Cellceutix has been able to go in this direction at a cost of virtually peanuts compared to other companies that instantly want to put hundreds of lives and hundreds of millions $$$ on the line for their studies.
So, simply, Cellceutix's plan is to see how it works and show the potential in a very targeted trial for ovarian cancer.
Clever and well thought out. That saves money. And lives.
Take a look at the PDF file from Cellceutix. Worth the read.
Also, some of the best cancer researchers in the world have been and are following their progress.
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Abstract Ovarian cancer (OC) is a molecularly and histologically heterogeneous disease; however, standard treatment is the same for all subtypes. High-grade serous OC initially responds to chemotherapy; however, low-grade serous and clear cell OC are relatively chemoresistant. Limited treatment options . are available upon recurrence. p53 mutations are found in over 90% of high-grade serous OC. Low-grade serous OC harbor wild type p53, but contain other mutations. During later stages of OC, tumors are a heterogeneous population of mutant cells; thus, development of a novel drug that addresses these molecular differences is highly desirable. Previously, we showed that Kevetrin stabilized wild type p53 and induced transcriptional targets in human lung carcinoma. We sought to validate Kevetrin as a potential treatment for OC with varied p53 status. Endometrioid carcinoma (A2780, wt p53), atypical non-serous clear cell (SKOV-3, deleted p53), and high-grade serous (OVCAR-3, mutant p53) OC cell lines were treated with Kevetrin. Kevetrin induced apoptosis in all three OC cell lines, as assayed by cleavage of PARP and caspase-3. Studies showed significant increases in p53 and p21 protein levels in A2780 cells in 24 to 48 hours; however, in OVCAR-3, Kevetrin downregulated oncogenic mutant p53. RNA levels of p53 and p21 were quantified by qRT-PCR 8 to 72 hours after treatment. No significant changes were observed in p53 mRNA, whereas an increase in p21 mRNA was observed in all three cell lines. In A2780, Kevetrin also induced levels of PUMA in a dose-dependent manner. To establish that Kevetrin mediates increased p21 expression requiring p53 in A2780 cells, p53 was depleted by siRNA. p53 depletion reduced p21 expression, as assayed by FACS, indicating p53 directs p21 expression in a dose-dependent manner after Kevetrin treatment. In an in vivo xenograft study in immunocompromised nude mice bearing established A2780 tumors, Kevetrin treatment inhibited tumor growth at well-tolerated doses. The mode of action in vivo also showed enhanced expression of p21 in tumor tissue, indicating p53 pathway activation in A2780 tumors. In contrast, in SKOV-3 cells and xenografts, a p53 independent increase in p21 expression was observed. In OVCAR-3 cells,Kevetrin altered the expression of three microRNAs (miRNA-27a, miRNA-1274b, miRNA-25), that are known to be dysregulated in OC, in a time-dependent manner. To gain further insight into the mechanism of action in cells with diverse p53 status, RNA-Seq is being performed in the three cell lines and tumor tissue from mice before and after Kevetrin exposure. In summary, Kevetrin has promise as an effective therapeutic agent for endometrioid, non-serous clear cell, and high-grade serous OC, with molecularly diverse p53 status. A Phase 1 clinical study was completed and a Phase 2 clinical study in ovarian cancer is scheduled to begin January 2017.
http://www.abstractsonline.com/pp8/#!/4292/presentation/3876
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Feel free to post your thoughts. For some reason I wanted to reply to one of our bashers *over there* with this.
Anyway, wanted to post it here as well. Very quickly put together so for that my apologies. Wife is waiting.
Cheers you guys!!
Kevetrin has only been taking steps forward so far. Certainly not without competition. If Cellceutix were the only company in the world working on cancer research, well then, cancer would be relatively unknown to mankind wouldn't it? Many companies have been working to reactivate P53 though that isn't the end game but seemingly a very optimistic goal. See page 14 of Cellceutix's Cancer Report https://static1.squarespace.com/static/571535...e+Vers.pdf
This shows Roch, Daichii Sankyo, Oprea failures. There are many others striving for the same goal including private companies. Interesting how even the private ones aren't as private as they seem if you have the money to invest with them, or maybe just know how to do the right DD to find them. Millions are poured into this research. Close to $40M placed into another one just this January.
So how is Cellceutix succeeding? Kevetrin, thus far has been shown to reactivate P53.
Lets see how the ovarian trial goes.
Just the basics are posted on the clinical trial site since we know so much more can be gained by the study...
Quote:Primary Outcome Measures: •Incidence of Treatment-Emergent Adverse Events [ Time Frame: 6 Weeks ]
Reporting of Adverse Events, and severity of adverse events
•Evaluate changes in biomarkers between pre-treatment sample and post-treatment sample [ Time Frame: 3 Weeks ]
Changes in RNA and/or protein level of pre-specified biomarkers associated with the p53 signalling pathway and apoptosis will be compared between pre-treatment sample (tumor biopsy, ascites fluid, and peripheral blood) and post-treatment sample (tumor biopsy, ascites fluid, and peripheral blood)
Secondary Outcome Measures: •Objective tumor response to treatment with Kevetrin [ Time Frame: 3 Weeks ]
Number of subjects in each response category (complete response, partial response, stable disease or progressive disease) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
•Plasma concentrations of Kevetrin [ Time Frame: 5 Days ]
Measurement of Kevetrin systemic concentrations
https://clinicaltrials.gov/ct2/show/NCT030427...amp;rank=2
I think what may be flagged by some is how Cellceutix has been able to go in this direction at a cost of virtually peanuts compared to other companies that instantly want to put hundreds of lives and hundreds of millions $$$ on the line for their studies.
So, simply, Cellceutix's plan is to see how it works and show the potential in a very targeted trial for ovarian cancer.
Clever and well thought out. That saves money. And lives.
Take a look at the PDF file from Cellceutix. Worth the read.
Also, some of the best cancer researchers in the world have been and are following their progress.
Quote:“What Cellceutix is doing with Kevetrin™ can lead to a groundbreaking moment in the world of oncology,” commented Cellceutix Scientific Advisor Dr. Emil Frei III, M.D. “In my career, including my tenure as Chief of Medicine at National Cancer Institute, I have seen countless companies throughout the world striving to bridge the gap between damaged or mutated p53 and carcinomas with little to no success. p53 can hold a vital key to the next generation of chemotherapy. Cellceutix’s discovery of Kevetrin™, which has been shown to reactivate p53 in a non-genotoxic manner, is a very promising advance in the fight against cancer.”
Quote:“What Cellceutix is doing with Kevetrin can lead to a groundbreaking moment in the world of oncology and is a vital key to the next generation of chemotherapy.”
— Dr. Emil Frei III
Quote:Cellceutix consultant Dr. Sylvia Holden commented, “I have been researching new drugs for nearly 30 years. Cellceutix is now a true pioneer in oncology discovery with this very special compound, Kevetrin. The Mechanism of Action of Kevetrin™, impacting both wild and mutant types of p53 to induce apoptosis and cell cycle arrest through multiple pathways while being well-tolerated, is what sets it apart from other chemotherapies today. Rather than being a traditional drug that targets and attempts to seek and destroy cancer cells independently, Kevetrin™ revitalizes p53 so that the body’s natural defense system eliminates the tumor on its own. As a stand-alone or combination front-line therapy, the magnitude of the potential of Kevetrin™ is simply unparalleled by anything that I have ever seen in the laboratory before.”
Dr. Krishna Menon, Chief Scientific Officer at Cellceutix commented, “I will be attending the American Society of Clinical Oncology (“ASCO”) Meeting in June to continue discussions regarding Kevetrin™. We anticipate that next year we will be presenting data from this year’s planned clinical trials.”
About Dr. Sylvia Holden: Dr. Holden received her PhD from Boston University followed by an NIH-funded post-doctoral fellowship at Dana-Farber Cancer Institute in the Division of Cancer Pharmacology headed by chemotherapy pioneer and Cellceutix Scientific Advisor Dr. Emil Frei III. Before joining Cellceutix, Dr. Holden was the Director of Pharmacology at EMD Serono in Billerica, MA (Merck KGaA) and Director of Tumor Biology at Shionogi BioResearch Corp., in Lexington, MA (presently Synta Pharmaceuticals). She was awarded 5 US patents and has published over 100 publications in peer-reviewed journals, including 12 first-authored papers and publications in Science and Nature Medicine.
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Abstract Ovarian cancer (OC) is a molecularly and histologically heterogeneous disease; however, standard treatment is the same for all subtypes. High-grade serous OC initially responds to chemotherapy; however, low-grade serous and clear cell OC are relatively chemoresistant. Limited treatment options . are available upon recurrence. p53 mutations are found in over 90% of high-grade serous OC. Low-grade serous OC harbor wild type p53, but contain other mutations. During later stages of OC, tumors are a heterogeneous population of mutant cells; thus, development of a novel drug that addresses these molecular differences is highly desirable. Previously, we showed that Kevetrin stabilized wild type p53 and induced transcriptional targets in human lung carcinoma. We sought to validate Kevetrin as a potential treatment for OC with varied p53 status. Endometrioid carcinoma (A2780, wt p53), atypical non-serous clear cell (SKOV-3, deleted p53), and high-grade serous (OVCAR-3, mutant p53) OC cell lines were treated with Kevetrin. Kevetrin induced apoptosis in all three OC cell lines, as assayed by cleavage of PARP and caspase-3. Studies showed significant increases in p53 and p21 protein levels in A2780 cells in 24 to 48 hours; however, in OVCAR-3, Kevetrin downregulated oncogenic mutant p53. RNA levels of p53 and p21 were quantified by qRT-PCR 8 to 72 hours after treatment. No significant changes were observed in p53 mRNA, whereas an increase in p21 mRNA was observed in all three cell lines. In A2780, Kevetrin also induced levels of PUMA in a dose-dependent manner. To establish that Kevetrin mediates increased p21 expression requiring p53 in A2780 cells, p53 was depleted by siRNA. p53 depletion reduced p21 expression, as assayed by FACS, indicating p53 directs p21 expression in a dose-dependent manner after Kevetrin treatment. In an in vivo xenograft study in immunocompromised nude mice bearing established A2780 tumors, Kevetrin treatment inhibited tumor growth at well-tolerated doses. The mode of action in vivo also showed enhanced expression of p21 in tumor tissue, indicating p53 pathway activation in A2780 tumors. In contrast, in SKOV-3 cells and xenografts, a p53 independent increase in p21 expression was observed. In OVCAR-3 cells,Kevetrin altered the expression of three microRNAs (miRNA-27a, miRNA-1274b, miRNA-25), that are known to be dysregulated in OC, in a time-dependent manner. To gain further insight into the mechanism of action in cells with diverse p53 status, RNA-Seq is being performed in the three cell lines and tumor tissue from mice before and after Kevetrin exposure. In summary, Kevetrin has promise as an effective therapeutic agent for endometrioid, non-serous clear cell, and high-grade serous OC, with molecularly diverse p53 status. A Phase 1 clinical study was completed and a Phase 2 clinical study in ovarian cancer is scheduled to begin January 2017.
http://www.abstractsonline.com/pp8/#!/4292/presentation/3876
==========================================================
===============++++++++++++++++++++++++++++++++
Feel free to post your thoughts. For some reason I wanted to reply to one of our bashers *over there* with this.
Anyway, wanted to post it here as well. Very quickly put together so for that my apologies. Wife is waiting.
Cheers you guys!!
8
