Veterinary researchers have harnessed the power of organoids, 3D structures grown from stem cells and tissue samples, to delve into the enigma of lung cancer in dogs. While relatively rare in canines, this disease is often lethal once diagnosed.
Organoids, these organ-like structures cultivated in labs, offer a superior window into complex biological processes compared to traditional 2D cell cultures. Originally designed for human research, this technology is now making its debut in canine lung cancer studies.
Published in the journal Biomedicine & Pharmacotherapy, this groundbreaking research shines a light on a severe issue in the canine world – canine primary lung cancer.
For dogs battling lung cancer, the outlook can be dire. Often, the disease is detected only when it has advanced significantly, leaving limited treatment options. Surgery to remove lung tissue (lung lobectomy) is common but often insufficient for advanced cases. Even with chemotherapy, the median survival time for dogs after lung lobectomy ranges from 160 to 450 days. For those with extensive cancer, survival drops to a mere 60 to 180 days.
Unlike in human medicine, where molecular targeted therapies have been revolutionary, veterinary medicine lags behind in this regard, leaving our furry companions with few choices.
Enter 3D organoid cultures, a cutting-edge technology mimicking living tissue dynamics better than conventional cell cultures. These miniature structures, grown from stem cells or tissue samples, self-organize into complex, organ-like formations – hence the name “organoid.” These structures allow researchers to explore intricate biological processes.
Veterinary researchers seized the opportunity to apply this technique to canine lung cancer, aiming to uncover new treatment avenues. They collected tumor samples from dogs with lung cancer and healthy lung tissue, creating canine primary lung cancer organoids (cPLCO) and canine normal lung organoids (cNLO).
The researchers aimed to replicate the tissue architecture of canine lung cancer more faithfully than previous cell culture attempts. Remarkably, cPLCO closely mirrored the characteristics of the original tumor tissues in terms of morphology (tissue shape and structure) and molecular profiles, including the expression of specific tumor markers. These markers, produced in higher amounts in cancer, provide crucial information about cancer aggressiveness and treatment response.
Moreover, different canine lung cancer strains exhibited varying sensitivity to anti-cancer drugs, opening doors to personalized treatment approaches.
The researchers also discovered a link between organoid cell viability and the expression levels of specific target molecules, such as Human Epidermal Growth Factor Receptor 2 (HER2) and Epidermal Growth Factor Receptor (EGFR). These proteins play pivotal roles in cell signaling, growth, and regulation, hinting at potential future therapies.
RNA sequencing revealed a significant increase in the activation of 11 genes associated with tumor proliferation in other cancers within the cancerous organoid.
Most intriguingly, the cancerous organoid showed enrichment in the Mitogen-Activated Protein Kinase (MEK) signaling pathway, crucial for cell proliferation, differentiation, and survival. The researchers tested a MEK inhibitor called trametinib, which significantly reduced the cancerous organoid’s viability and inhibited tumor growth when grafted onto healthy cell models.
The creation of dog lung cancer organoids offers a potent tool to scrutinize the disease in unprecedented detail, potentially leading to more effective treatments for our four-legged friends. It may also influence human lung cancer research, offering fresh diagnostic markers and therapeutic targets.
Source: Tokyo University of Agriculture and Technology
