Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.
As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.
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Interview with Dr. Gregory J. Riggins from Johns Hopkins University
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Dr. Gregory Riggins from Johns Hopkins University discusses his 2017 study published by Oncotarget, entitled, "Synergistic and targeted therapy with a procaspase-3 activator and temozolomide extends survival in glioma rodent models and is feasible for the treatment of canine malignant glioma patients."
So this work with the procaspase-3 activating compound or PAC-1 started several years ago when we saw a paper from Paul Hergenrother that he had developed a new procaspase-3 activating compound that looked very promising. It's a first-in-class drug. It cleaves procaspase-3 to activate caspase-3, and that's in the executioner phase, and it is less likely to have drug resistance because it's at the end of the apoptosis cascade.
A talented post-doctoral fellow in the laboratory Avadhut Joshi saw that this drug got into the brain. In fact, the first publication from Paul suggested that this drug should be reformulated because it gets into the brain and they were trying to avoid any side effects from having the drug enter the CNS.
Figure 2: PAC-1 and TMZ induce synergistic cell death in glioblastoma cells.
We work on glioblastomas, which is a very challenging cancer of the brain. It's one of the most lethal of the brain tumors, and we want drugs to get into the brain. In fact, that's half the challenge for developing new chemotherapies is getting the chemotherapy into the brain in sufficient concentrations. So we requested the drug, we formed the collaboration, and we've worked on this for years, looking at rodents, and then Paul's group has also studied this exclusively.
And as reported in this paper, in dogs that have spontaneous brain tumors and their owners bring them in, their companion canines, and we've tested the combination of PAC-1 and temozolomide to show that it's feasible in these large animals to treat glioblastomas.
This has been exciting work for us. It has led to a phase one clinical trial that is now at the University of Illinois and at Johns Hopkins here in Baltimore, where we're looking at both the safety in metastatic tumors and then now in glioblastomas. One of the aspects of this work is that we show that it works in combination with temozolomide, which is an outcome alkylating agent, it damages the DNA, and it helps trigger apoptosis. And it is synergistic with PAC-1. When used together, they form a improved response, at least in the animals, and we are hoping that we will get along far enough that we can show the synergistic response in glioblastoma patients.
So our next steps are to complete this safety trial on PAC-1 and that has reached some of its important objectives already where we've shown that we can move up safely in dosing. And we are now moving on to the phase where we can combine PAC-1 with temozolomide for glioblastoma patients.
