Predict Response To Cancer Treatment?

Issue 20 Volume 8

Hello, Summarians!

Life has gotten expensive, especially medical care. It doesn’t matter what species of animal you are; costs have risen dramatically. This issue includes some of the newest high-tech ways to improve our medical care, but also asks us to consider the issue of cost.

How does the spectrum of care fit into our daily lives? I don’t have all the answers, but it is time that we start pondering the questions.

Emergencies and Spectrum of Care

This study investigated how emergency veterinarians respond to owner-reported financial limitations (ORFLs) in common treatable emergencies. An anonymous survey collected responses from 168 emergency veterinarians about their recommendations for cases where clients could not afford the proposed treatment plans. The results showed a wide variety of approaches depending on the scenario. Recommendations included returning the patient to a primary care veterinarian, referring to shelters or high-quality, high-volume (HQHV) spay-neuter clinics, performing procedures themselves, surrendering the pet, or euthanasia. 

Although a spectrum-of-care approach is increasingly advocated, options in emergency settings often remain limited. Not all clinicians were aware of alternatives such as HQHV clinic referral, which was infrequently selected even when evidence supported it as a reasonable option (for example, in stable pyometra cases). Life-threatening conditions, like dystocia or gastrointestinal foreign bodies, frequently led to euthanasia recommendations, highlighting the tension between urgency, available resources, and hospital policies. 

The study also underscored how ORFLs contribute significantly to moral distress and dissatisfaction among veterinarians, with many feeling powerless when unable to offer affordable care. This is compounded by factors such as fixed hospital pricing, limited surgical experience among some emergency clinicians, and the corporate structures of many practices that restrict flexibility. 

Overall, the findings point to the need for improved partnerships between emergency hospitals, general practitioners, shelters, and HQHV clinics to expand access to care. Training emergency veterinarians in additional surgical procedures and fostering community networks could also help mitigate barriers. The study acknowledged limitations, including potential survey bias and the hypothetical nature of the scenarios, and called for further research to identify effective strategies to improve care access and reduce moral distress in emergency veterinary practice. 

Wilcox, Z., McCobb, E., Dowling-Guyer, S., & Rozanski, E. (2025). Emergency clinicians need more information about offering a spectrum of care and solutions for clients with financial limitations. Journal of the American Veterinary Medical Association https://doi.org/10.2460/javma.25.01.0034 

Bottom line — There are some possible answers to this frustrating situation

Genetic Markers and Clinical Outcomes for Lymphoma

This study explored the genetic landscape of canine lymphoma and its relationship to clinical outcomes, leveraging targeted next-generation sequencing (tNGS) of 308 cancer-relevant genes in 238 dogs with lymphoma. Canine lymphoma, mirroring human non-Hodgkin lymphoma in heterogeneity and genetic underpinnings, represents a significant proportion of canine cancers. Prior research had largely focused on B-cell lymphomas (BCL), with less known about the genetic drivers and prognostic markers of T-cell lymphomas (TCL). 

The analysis revealed several genes of prognostic significance. In BCLs, somatic loss-of-function mutations in TRAF3 were associated with longer overall survival (OS) and progression-free survival (PFS), suggesting enhanced sensitivity to chemotherapy, potentially through dependence on non-canonical NF-κB signaling. Conversely, in TCLs, somatic mutations in PIK3CD and CREBBP correlated with shorter PFS when treated with CHOP-like or CCNU-containing regimens. PIK3CD mutations likely promote the constitutive activation of survival pathways such as PI3K/AKT/mTOR, diminishing chemotherapy efficacy. CREBBP loss impairs histone acetylation and tumor suppressor gene expression, potentially contributing to chemoresistance, though such tumors may be sensitized by histone deacetylase inhibitors. 

Other notable findings included mutations in NOTCH2 and KMT2C in TCLs and KMT2D in BCLs, with KMT2 mutations linked to longer PFS in some cases, though their prognostic relevance remains inconsistent across cancer types. SETD2 and SATB1 mutations were recurrent in BCLs and TCLs, respectively, reflecting their known roles in epigenetic regulation and T-cell differentiation, though SETD2 mutations did not significantly impact survival in this cohort. 

Immunophenotyping confirmed the cohort was broadly representative of clinical lymphoma subtypes, with BCLs predominating. However, the findings may not generalize to less common T-cell subtypes like double-negative or T-zone lymphoma. The use of whole blood as the germline comparator posed challenges in distinguishing somatic from low-frequency circulating tumor variants, mitigated by conservative allele frequency thresholds. 

The study highlighted the potential of integrating genomic profiling into veterinary oncology, identifying driver mutations with prognostic and potentially therapeutic relevance. It underscored the need for further functional validation of mutations, broader subtype representation, and larger breed-controlled cohorts. While the results advance precision oncology in dogs, translating these insights into routine clinical practice will require expanded studies, assessments of copy number alterations, and possibly whole-exome or whole-genome sequencing to capture the full mutational landscape. 

Tsang, J., Yap, Q.J., Kapoor, S. et al. Identification of novel genetic mutations for the treatment prognostication of canine lymphoma. npj Precis. Onc. 9, 174 (2025). https://doi.org/10.1038/s41698-025-00988-5 

Bottom line — Early results support this as a potential tool.

Safety of Injectable Hydrogels

This study examined whether the injectable hydrogel 2.5 iPAAG, the active component in Arthrosamid®, Arthramid®, Bulkamid®, and Mictamid®, exerts neurotoxic effects in vitro. These products, used in humans and animals to treat osteoarthritis and urinary incontinence, contain crosslinked polyacrylamide polymerized from acrylamide (AM), a known neurotoxin. Regulatory concerns have questioned whether residual AM could account for their pain-reducing effects by damaging sensory neurons. 

To address this, human iCell® GlutaNeurons derived from induced pluripotent stem cells were exposed to up to 20% 2.5 iPAAG for 96 hours. Neuronal viability, cell death, apoptosis, and neurite network formation were assessed. Negative controls (Fish Gelatin) did not negatively impact neuronal health, while positive controls (acrylamide, A23187, and Tunicamycin) caused marked reductions in cell survival and neurite networks, with AM and A23187 inducing pronounced cytotoxicity and neurite degeneration, and Tunicamycin increasing apoptotic death. 

In contrast, 2.5 iPAAG showed no statistically significant adverse effects on cell survival, non-apoptotic or apoptotic cell death, or neurite networks compared to untreated controls. While both Fish Gelatin and 2.5 iPAAG demonstrated a mild trend toward increased neurite network formation, this effect was likely mechanical rather than chemical. 

The study also emphasized that 2.5 iPAAG has passed extensive biocompatibility testing and, in real-world use, degrades negligibly in vivo. Residual monomer content is minimal, with potential exposure far below typical dietary intake levels. 

Overall, the findings demonstrate that 2.5 iPAAG does not exhibit apparent in vitro neurotoxicity or cytotoxicity in human neurons, supporting its continued use in medical and veterinary applications without evidence that its pain relief arises from neurotoxic mechanisms. 

Walmod Peter S., Kusk Philip, Jøhnk Nina, Ankorina-Stark Ieva, Essex Anthony. An injectable 2.5% cross-linked polyacrylamide hydrogel (2.5 iPAAG) demonstrates no neurotoxicity in human induced pluripotent stem cells-derived iCell® GlutaNeurons Frontiers in Toxicology Volume 7–2025 2025 https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2025.1585430 DOI=10.3389/ftox.2025.1585430 ISSN=2673-3080  

Bottom line — Yes, they are.

Just putting things in perspective …

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