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Trying to gain on glioblastoma
UPPSALA, Sweden—Aimed at ultimately blasting glioblastoma, an aggressive tumor that carries an almost surefire death sentence, Beactica AB has launched a new research collaboration with Uppsala University and the Science for Life Laboratory (SciLifeLab, which is affiliated with Uppsala) to study the effects on brain cancer stem cells of specific small molecules under development by Beactica.
Patients with glioblastoma, on average, only survive 15 months after diagnosis, and the cancer in most cases is fatal. Scientists believe that the difficulties in treating the disease are caused by cells in the tumors called glioma-initiating cells (GICs), defined as similar to stem cells, that can start growing again—even after treatment.
In a study published Dec. 13, 2016, in the journal Cell Reports, scientists from Uppsala University indicate that a type of stem cell in the tumor is present in different states, with different responses to drugs and radiation. This may open a door leading to the development of new treatment strategies designed to reverse therapy-resistant cell states.
If successful, this discovery and resulting treatment strategy would have significant lifesaving effects on brain cancer patients across the globe.
The early, specific goal of the collaboration is to evaluate and characterize the preclinical efficacy of Beactica’s allosteric modulators of the epigenetic protein LSD1 in glioma-inducing cells, according to Uppsala researchers. The collaboration will also evaluate Beactica’s compounds in combination with multiple other anticancer agents.
But scientists immersed in this venture are still on the starting blocks and have a way to go before reaching the proverbial finish line.
The collaboration is the brainchild of Uppsala University’s Faculty of Medicine faculty members Prof. Bengt Westermark and Dr. Anna Segerman, who have developed a unique capability to study glioma-initiating stem cells with cell clones established from fresh biopsies and characterized to genotype, phenotype and treatment response including standard-of-care treatment for glioblastoma.
The Beactica/Uppsala research will be conducted at the In Vitro and Systems Pharmacology Facility of the SciLifeLab Drug Discovery and Development Platform. A Swedish national center for molecular biosciences, with the mission to develop, use and provide advanced technologies, SciLifeLab was created through the concerted efforts of four academic institutions in Sweden: Uppsala University, Karolinska Institutet, KTH Royal Institute of Technology and Stockholm University.
“We are eager to apply our expertise and capabilities to help Beactica deliver promising therapies,” Westermark stated in a press release. “The company’s LSD1 program is impressive and has the potential to address the largely unmet medical need of glioblastoma patients.”
Segerman, lead researcher at the glioma clone platform, adds, “Early results from the collaboration indicate a potential to enhance the effect of established treatment in glioblastoma cells.”
Dr. Per Källblad, CEO of Beactica, states, “We are excited to take this next step in our relationship with Uppsala University and SciLifeLab. These studies will provide important insights into our compounds’ ability to show efficacy in a cancer with extremely poor prognosis. We want to stake out a path for a first-in-class therapeutic that will benefit patients.”
Segerman wrote in an article entitled “Therapy response in brain tumor cells is linked to disease prognosis” that: “The new results from Uppsala University show that a single tumor contained GICs in different states are differently resistant to therapy. Cell states that were resistant to radiation were also resistant to drugs, and cell states that were resistant to one drug tended to be resistant to most of the other tested drugs.”
“Another interesting result was that the GICs did not fall into distinct response groups. Instead, the difference in their response can best be described as a continuum of cells with different resistance levels,” she continued. “We also discovered a relationship between the resistance level and molecular characteristics of the tumor that are associated with disease prognosis. A resistant cell state of the GICs was linked to characteristics associated with poor prognosis, and a sensitive cell state was linked to characteristics associated with better outcome.
“A new strategy to treat glioblastoma could be to target the intertumor heterogeneity, i.e. the presence in the same tumor of a mix of GICs that have different resistance levels and are linked to different prognoses.”
Segerman’s Uppsala colleague Westermark concludes, “We hypothesize that the mix of GICs with different resistance levels is formed by a drift between the different cell states. With more knowledge about the mechanisms behind this, it might be possible to develop new therapies that reprogram the GICs to render them more sensitive to radiation and drugs.”