A Small Sample of CSF Research Activities
Articles & Resources
NOVEMBER 2020 RESEARCH UPDATE
From 2014-2016, CSF did all within it’s power to help bring 3 new promising therapies into phase 1 clinical trials that are specific to Ewing’s. It took quite a bit of time & $ to get through all pre clinical testing/FDA requirements but with the help of CSF and many others, this became a reality for all three therapies. Please see below for specifics.
Current Targeted therapies for relapsed Ewing’s patients (all Phase 1)
Oncternal TK216/ TK 216 + Vincristine (see last article)
SALARIUS SP-2577 (LSD1)
GRADALIS Pbi-shRNA™ EWS/FLI1 Type 1 LPX
CSF Combination research
(PDX/Microdevise) MD Anderson, Dr. Joseph Ludwig
With 3 targeted therapies in clinical trials, CSF decided to move into another very promising area of research. Combination Therapy. CSF does not believe in the MAGIC bullet theory. The idea that ONE therapy can cure Ewing’s or any other cancer for that matter. Yes, there are some examples but they are extremely small in number.
PDX (Dr. Joseph Ludwig, MD Anderson)
CSF partnered with Dr. Joseph Ludwig of MD Anderson in early 2016 and began to build a PDX (Patient Derived Xenograph) “factory” in order to accomplish multiple Ewing’s combination testing concurrently. PDX is simply the process of utilizing a patients own tumor which is then implanted into a mouse for testing. The norm is to utilize immunosuppressed nude female mice with cell lines when testing combinations. Unfortunately, we (and many others) feel this method is outdated and rarely is a good predictor for measuring patient outcomes to specific combinations . The PDX format gives researchers an improved microenvironment for testing combination therapies.
As of March of 2018, we have 500+ PDX mice. Ewing’s combination testing is under way and our goal is to keep this resource strong. Additionally, we have opened this resource up to Ewing’s researchers, other Ewing’s foundations & Pharma companies (Pharma must pay nominal fee and MUST be Ewing’s related). Two of the three clinical trials stated above are utilizing PDX testing to help push their therapies forward (should combinations increase the level of efficacy). We’re happy to report that we have multiple combinations that look promising in early testing against Ewing’s. We hope these combination therapies continue to show promise and we are thus able to begin clinical trials as soon as possible.
Microdevise (Dr. Joseph Ludwig, MD Anderson)
Imagine a grain of rice with 18 reservoirs. Each one of these reservoirs can hold a therapeutic combination or individual therapy that could potentially have activity against Ewing’s. We are currently working with Dr. Ludwig and MD Anderson to help push this devise forward and ensure that Ewing’s is at the forefront of this technology.
Now, imagine a Ewing’s patient (or any cancer patient for that matter) who is able to have this grain of rice implanted surgically, 18 combinations released and 24 hrs later have the microdevise removed with a portion of the cancerous tissue. Researchers can then look at the tissue and see what combination worked/didn’t work. We believe this is the next “level” when it comes to improving the cancer microenvironment for combination testing. Please see attachment for more information/visual representations.
Dr Ludwig is working with engineers at MIT to devise a potential improvement when studying combination therapy. A microdevise that could completely alter how anti-cancer drug development occurs in the future. If early tests establish it’s viability, the microdevise could eventually allow scientists to directly study drug efficacy within actual human tumors, eliminating the costly & time consuming step of completing pre clinical research in human animals. Plus, the microdevise could simultaneously access tumor response in 18 medicines or therapeutic combinations in the same amount of time traditionally needed to evaluate just one drug. If the technology can be validated, it could dramatically accelerate drug discovery in Ewing’s by 10-20 fold.
CSF New Project, 2018/2019
Utilizing evolutionary biology of Ewing’s Sarcoma in order to help us make smarter decisions while treating patients who have relapsed and/or have refractory disease. (Dr. Jacob Scott, Cleveland Clinic)
Dr. Scott’s work aims to use evolution to help teach doctors what chemotherapies a patient's tumor will respond to. To do this, he is using experimental evolution and state of the art genomics to describe how Ewings changes during therapy, and to make a map, or matrix, or description of tumor weaknesses exposed during this process. We all know that Ewings changes during therapy as it learns how to beat whatever chemo lays in it's path. What Dr. Scott's work has shown in lung cancer is that during that process, as the cancer evolves resistance, it sometimes also becomes very specifically sensitive to other drugs- sort of a cost to it's learning to be resistant to the drug in front of it. Dr. Scott's work seeks to create a matrix (or lookup table) whereby Ewing’s clinicians will be able to compare the current genetic makeup of the patient's tumor with those he observes during the controlled evolution experiments, so they can understand what sensitivities a specific patient's tumor has at the time of relapse.
We are excited to report that the NIH just gave this project a $350,000 grant based off a project that CSF initiated.
Please see below attachments for further info,
Dr. Scott Chess (explains hypothesis via chess)
Dr. Scott Matrix (past scientific publication on same strategy utilized against other cancers)
Improvement of clinical trials for Ewing’s Sarcoma patients