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Research uncovers how prostate cancer cells resist treatment

Researchers at Texas A&M Health have identified a molecular mechanism that increases cholesterol levels inside prostate cancer cells—an important process that may help explain how some tumours progress and become resistant to treatment.
The study, led by Ziying Liu, a former student in the lab of Fen Wang, at the Institute of Biosciences and Technology and the Naresh K Vashisht College of Medicine, found that a cell signalling receptor called fibroblast growth factor receptor 1 (FGFR1) helps prostate cancer cells increase their internal supply of cholesterol.
When the research team removed FGFR1 from prostate cancer cells, cholesterol levels dropped. Genes responsible for taking up low-density lipoprotein (LDL) and producing cholesterol within the cell became less active.
The standard first-line treatment for prostate cancer is androgen deprivation therapy (ADT). Although many patients initially respond to this therapy, most cases progress within one to three years to a more aggressive form known as castration-resistant prostate cancer.
One of the biological processes contributing to this transition is steroidogenesis—the production of steroid hormones derived from cholesterol. Because these hormones can fuel tumour growth even when androgen levels are suppressed, understanding how cancer cells obtain and regulate cholesterol has become an important focus of prostate cancer research.
By clarifying the molecular mechanisms that control cholesterol metabolism in prostate cancer cells, the research may help identify potential targets for future therapies aimed at slowing or preventing disease progression.
“Cancer cells frequently rewire metabolic pathways to sustain growth, and evade therapeutic treatment,” Wang said. “Our group has previously shown that aberrant FGFR1 signalling drives several metabolic programmes in prostate cancer, including glycolysis, choline metabolism and iron metabolism. This study adds cholesterol metabolism to that list and further highlights FGFR1 as a multifunctional pathway that could be exploited for future immunotherapy strategies.”
The post Research uncovers how prostate cancer cells resist treatment appeared first on Drug Discovery World (DDW).
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New webinar: Tackling drug discovery challenges in cancer research

Hosted by Drug Discovery World and supported by Sartorius and BioIVT, this webinar will explore the opportunities and challenges that exist within cancer research drug discovery and development.
You will hear from Dr Sudha Rao, Chief Scientific Officer of Kazia Therapeutics, Karol Budzik, PhD, Business Development Associate at Vyriad Therapeutics and Lars van der Veen, Chief Scientific Officer at iOnctura.
Presentations will cover how cancer treatments have shifted towards reprogramming the biology driving tumour growth, immune escape and treatment resistance, the trajectory that in vivo CAR-T treatments are taking, and how challenging tumours burdened by stroma and immune-mediated resistance can be tackled.
Q&A with the speakers follows the presentations.
The post New webinar: Tackling drug discovery challenges in cancer research appeared first on Drug Discovery World (DDW).
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Psilocybin proves promising in neuropathic pain mouse study
Amid the rise of psychedelics in the mental health space, researchers have begun to explore psilocybin as a treatment for chemotherapy-induced peripheral neuropathy.
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New Spectrometry Technique Could Aid Formulation Development
New Spectrometry Technique Could Aid Formulation Development
A new technique combining two forms of spectrometry could help biopharmaceutical companies improve their choice of formulation buffer for antibody manufacturing by revealing how molecular forms and three-dimensional shapes of complex biologics respond to their environment. That’s the view of Christian Bleiholder, PhD, a professor at Florida State University who helped develop the technique.
According to Bleiholder, what happens structurally when a complex biological molecule, such as an antibody or viral spike protein, binds to its target is currently poorly understood.
“This is where [this approach] can help with the bioprocessing and formulation,” he says, as structural changes “can affect the lifespan [of the product] and lead to issues, such as aggregation.”
Because antibodies are complex, existing techniques tend to be powerful at different levels of complexity, he explains. Mass spectrometry is particularly powerful for distinguishing molecular composition, while structural approaches such as X-ray crystallography and cryo-electron microscopy can provide high-resolution structural information.
The challenge is understanding the link between these things within a heterogeneous sample, he says.
To overcome this, Bleiholder and his team worked with Bruker Daltonics to develop Tandem-Trapped Ion Mobility Spectrometry (Tandem-TIMS). This combines tandem ion mobility spectrometry with tandem mass spectrometry to disentangle three overlapping layers of molecular complexity: molecular form, three-dimensional shape, and binding or assembly state, he says.
He explains that, if the proteins have different structures, they can be characterized with tandem ion mobility spectrometry, and then mass spectrometry can be used to look at their molecular forms and binding states.
Going forward, Bleiholder hopes the technique can be used for formulation development but also earlier, during drug discovery of new products, such as multi-specific antibodies, to determine which molecular states are important and how those change when a biologic engages its target. He also plans to look at automating the technique.
Bleiholder spoke about using Tandem-TIMS at the Bioprocessing Summit in Boston earlier this year.
The post New Spectrometry Technique Could Aid Formulation Development appeared first on GEN – Genetic Engineering and Biotechnology News.
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