Pediatric Consortium Study

[biopearl123]

We have previously discussed the recent completion of the previously terminated (2016) Pediatric Consortium Study which was forced to close early due to unfortunate intra cerebral hemorrhages in two patients. We have discussed possible etiologies for the bleeds but mostly this was likely related to Imetelstat induced thrombocytopenia and friable tissue, not to mention unknown factors like surgery, biopsy etc. I and others have posted previously about the curious updates to this study with no elaboration until the recent posting of "results." If one looks at the other studies before the MF and MDS studies few if any have results posted. This includes the MM study, and solid tissue studies (although some had published finding in the medical literature or presentations at meetings), the clinical trials site was none the less not updated with "results" with the notable exception of the Pediatric Consortium Study. This suggests that Janssen/ Geron is setting the stage for a follow on study now that much more is known about dosing. IMHO, FWIW. bp

[jpheis]

I found this on anr2018.org. A Molecularly Driven Pharmacological Approach for Neuroblastoma: Targeting TERT and CKS1b
Neuroblastoma is the most common extracrainal solid tumour in childhood. The high risk, metastatic form of neuroblastoma has very poor prognosis, and the survival rate after 5 years is of only about 50% in the face of aggressive treatments. The protooncogene and transcription factor MYCN is a direct cause of the disease when activated by amplification in a fraction (30%) of high-risk neuroblastomas. Using a genome- wide shRNA screen, we have recently unveiled a network of druggable MYCN synthetic lethal genes. One of the synthetic lethal interactors identified in the screen is CKS1b, inhibited by the small molecule fluoxetine, also known as Prozac. Fluoxetine is an antipsychotic drug and due to its relatively low toxicity profile is also used in the context of childhood behavioural control. Another important genomic rearrangement present in about a third of high risk neuroblastomas occurs in the chromosomal 5p15.33 region, proximal to the telomerase reverse transcriptase gene (TERT). Notably, an oligonucleotide inhibitor of TERT activity developed by the biotech company Janssen, Imetelstat, has been recently used in multiple clinical trials for human solid and haematological malignancies.
In vitro, both Fluoxetine and Imetelstat reduced neuroblastoma cell proliferation and caused apotosis of MYCN-amplified neuroblastoma cell lines. The effect was much more pronounced when the drugs were used in combination. In vivo, the combination of Fluoxetine and Imetelstat significantly reduced the growth of small but not large tumour masses. Interestingly, Fluoxetine alone showed antitumour activity if treatments were started shortly after subcutaneous tumour cells inoculations.
In conclusion, Fluoxetine and Imetelstat could represent potential candidates for second line therapy in relapsing neuroblastoma.

[biopearl123]

This is a a very interesting article. Who would have thought that an antidepressant would have anti tumor activity. (I could see where it might help attitude at least). It just goes to show that so many compounds have been testing in the search for anti neoplastic agents (including vitamin C for Linus Pauling fans). In it's hey day Geron was said to have tested over 1 million compounds in its search for other agents with telomerase inhibition activity. bp