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Genetic pattern key to colorectal cancer, research shows 

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Colorectal cancer

A genetic pattern could explain how colorectal cancer develops, new research suggests. 

Findings from ChristianaCare’s Helen F Graham Cancer Center & Research Institute identified a developmental genetic pattern that helps explain how colorectal cancer develops, why it becomes aggressive and how long patients are likely to survive. 

The study, published in Stem Cells Translational Medicine, shows that when normal cell signalling pathways fall out of balance, colon stem cells stop maturing and begin to overgrow. This disruption alters key developmental genes, known as HOX genes, driving cancer growth and resistance. 

The team identified an eight‑gene HOX signature that strongly predicts poor survival in colorectal cancer patients, making it a powerful marker of disease behaviour and a potential target for future therapies. 

“Cancer cells don’t just grow,” said Bruce Boman, Senior Researcher at ChristianaCare’s Cawley Center, who led the study. 

“They adapt by activating early developmental programmes. This flexibility helps them survive therapy.” 

Findings could help ‘improve long-term outcomes for patients’

Research shows the HOX gene network contains 39 transcription factors critical for animal embryonic development. The exact timing of HOX gene expression dictates proper embryo development and, according to findings, dysregulation of this precise timing is linked to colon cancer formation. 

HOX genes normally guide early cell development and are tightly controlled in healthy tissue. The researchers found that when WNT signalling becomes overactive and retinoic acid signalling is disrupted, HOX genes become misregulated in colon stem cells. 

Instead of maturing, these stem cells multiply, with overpopulation fuelling tumour growth and leading to more aggressive disease. 

“This explains why tumours that look similar can behave very differently in patients,” said Brian Osmond, Lead Author of the study.  

“The difference lies in which developmental programme the cancer is using.” 

Because HOX genes are closely tied to WNT and retinoic acid signalling, the researchers suggest that carefully designed combination therapies could help restore balance in cancer stem cells and limit resistance. 

“These cancers are using normal developmental tools in the wrong context,” Boman added.  

“If we can interrupt that process, we may be able to improve long‑term outcomes for patients.” 

 

 

 

 

 

The post Genetic pattern key to colorectal cancer, research shows  appeared first on Drug Discovery World (DDW).

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New webinar: Tackling drug discovery challenges in cancer research

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Cancer cells

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.

Register for free now.

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

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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

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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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