- |||||||||| Jakafi oral (ruxolitinib) / Novartis, Incyte
Identifying and Treating “Progression” in Myelofibrosis () - Sep 26, 2019 - Abstract #SOHO2019SOHO_257; P2a/2b KRT-232 is an oral MDM2 inhibitor that has also entered the clinic in this setting (NCT03662126)...Besides CPI-0610, these include the phosphatidylinositol-3-kinase delta isoform inhibitors parsaclisib20 and umbralisib,21 the BH3-mimetic navitoclax, the heat shock protein 90 antagonist PU-H71, etc. Table 3 lists three such trials, early results from which have been presented. Like ruxolitinib failure, there is also no uniformly accepted definition of sub-optimal response to ruxolitinib, and various criteria are in use.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Journal: Imetelstat, a telomerase inhibitor, is capable of depleting myelofibrosis stem and progenitor cells. (Pubmed Central) - Aug 28, 2019 These actions of imetelstat on MF HSCs/HPCs were associated with inhibition of telomerase activity and the induction of apoptosis. Our findings indicate that the effects of imetelstat therapy observed in MF patients are likely attributable to the greater sensitivity of imetelstat against MF as compared with normal HSCs/HPCs as well as the intensity of the imetelstat dose schedule.
- |||||||||| Jakafi oral (ruxolitinib) / Novartis, Incyte
Journal: Novel treatments to tackle myelofibrosis. (Pubmed Central) - Apr 28, 2019 Despite the dramatic progress made in the treatment of patients with myelofibrosis since the introduction of the JAK1/2 inhibitor ruxolitinib, a therapeutic option that can modify the natural history of the disease and prevent evolution to blast-phase is still lacking...Expert commentary: The most mature advances in treatment of myelofibrosis are the development of second-generation JAK1/2 inhibitors and improvements in expanding access to donors for transplantation. In addition, there are efforts to identify drugs that target pathways other than JAK/STAT signaling that might improve the survival of myelofibrosis patients, and limit the need for stem-cell transplantation.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Review, Journal: Oligonucleotides Targeting Telomeres and Telomerase in Cancer. (Pubmed Central) - Dec 13, 2018 Specifically, GRN163L and T-oligos have demonstrated promising anticancer activity in multiple cancers types via induction of potent DNA damage responses...This review aims to provide a comprehensive understanding of current oligonucleotide-based anticancer therapies that target telomeres and telomerase. These studies may help design novel therapeutic approaches to overcome the challenges of oligonucleotide therapy in a clinical setting.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Trial completion, Trial completion date, Trial primary completion date: Imetelstat Sodium in Treating Participants With Primary or Secondary Myelofibrosis (clinicaltrials.gov) - Jul 20, 2018 P2, N=81, Completed, Trial completion date: Oct 2021 --> Feb 2022 Active, not recruiting --> Completed | Trial completion date: Jan 2019 --> May 2018 | Trial primary completion date: Jan 2019 --> May 2018
- |||||||||| imetelstat (GRN163L) / Geron
Trial termination: Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors (clinicaltrials.gov) - Jul 20, 2018 P2, N=43, Terminated, Active, not recruiting --> Completed | Trial completion date: Jan 2019 --> May 2018 | Trial primary completion date: Jan 2019 --> May 2018 Completed --> Terminated; Due to several intracranial hemorrhages and recommendation by the PBTC DSMB.
- |||||||||| Review, Journal: Developmental Therapeutics in Myeloproliferative Neoplasms. (Pubmed Central) - Apr 24, 2018
In polycythemia vera, a novel interferon administered every 2 weeks is being developed for front-line therapy in high-risk individuals, and inhibitors of human double minute 2 (HDM2) have shown promise in preclinical studies, as have HDAC inhibitors such as givinostat (both in the laboratory and in the clinic). Ruxolitinib is approved for second-line therapy of polycythemia vera and is being developed for essential thrombocythemia.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Biomarker, Journal: Epigenetic landscape of the TERT promoter: a potential biomarker for high risk AML/MDS. (Pubmed Central) - May 18, 2017 The activity of the telomerase inhibitor, imetelstat, was measured using leukaemia cell lines...AML cell lines and primary blasts harbour distinct TERTpro/Ex1 methylation profiles that could serve as a prognostic biomarker of AML. However, validation in a large cohort of patients is necessary to confirm our findings.
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