Canine and Feline Oncology: Targeted Therapies and Immunotherapy Protocols

Canine and feline oncology (CFO) faces rising incidence due to increased lifespan, improved diagnostics (MRI, CT, PET-CT), and heightened owner awareness. Conventional tx (surg, chemo, RT) remains foundational but limited by toxicity, recurrence, and metastasis. Targeted therapies (TTx) and immunotherapy (ITx) represent paradigm shifts in CFO, leveraging molecular oncology (MO) to enhance specificity and efficacy. TTx inhibit oncogenic drivers via small molecules or mAbs. Key targets: RTKs (e.g., c-KIT, VEGFR, PDGFR), MAPK/ERK, PI3K/AKT/mTOR, JAK/STAT. Toceranib phosphate (Palladia®) — multitargeted RTK inhibitor — FDA-approved for canine cutaneous mast cell tumors (cMCT) with c-KIT mut (exon 11 del/ins). Response correlates with mut status; resistance via secondary mut (exon 17) common. Masitinib (Kinavet®) — selective c-KIT inhibitor — used in cMCT and non-resectable GISTs. Epertinib (unapproved) — EGFR inhibitor — trialed in feline SCC. mTOR inhibitors (e.g., rapamycin, temsirolimus) show activity in canine lymphoma (CL) and hemangiosarcoma (HSA), esp. in PI3K-dysregulated cases. BRAF V600E mut — rare in dogs but reported in cMCT, HSA, TCC — targeted by vemurafenib/dabrafenib (limited data). PARP inhibitors (olaparib) under eval in BRCA-mut canine mammary tumors (CMT). ITx harness immune system: includes cancer vaccines, immune checkpoint inhibitors (ICI), CAR-T, oncolytic viruses (OV), and cytokine therapy. First FDA-approved cancer vaccine: Oncept® (canine melanoma vaccine) — xenogeneic tyrosinase DNA vaccine — prolongs survival in stage II/III oral melanoma (MO) post-surg. Mechanism: cross-priming of anti-tyrosinase T-cells. Limitations: weak abscopal effect, immunosuppressive TME. Feline fibrosarcoma (FFS) vaccine (Oncept Feline) — same platform — reduces recurrence post-resection in FeLV/Vac-associated FFS. ICI: anti-PD-1/PD-L1 mAbs — limited by lack of validated canine mAbs; CHOP (canine PD-1) mAb (e.g., c4G12) in trials for CL, OS, HSA. Challenges: immune-related adverse events (irAEs), hyperprogression, low TMB in many tumors. CAR-T: preclinical in canine B-cell lymphoma using anti-CD20 CARs; hurdles include T-cell exhaustion, trafficking, and antigen escape. OV: CAV-2, VV, HSV engineered to express GM-CSF or immune stimulants; intratumoral delivery in sarcomas, carcinomas. Cytokines: IL-2, IFN-α used as adjuvants; rhIFN-ω (Virbagen Omega®) approved in EU for feline leukemia virus (FeLV) and adjunct in lymphoma. Biomarker-driven tx selection critical: NGS panels (e.g., OncoK9®, QuickVet® MAP) detect actionable mut (c-KIT, BRAF, PI3K), CNVs, fusions. Liquid biopsy (ctDNA) enables MRD monitoring and early relapse detection. TME profiling (IHC, multiplex IF) guides ITx suitability (e.g., CD8+ TIL density predicts ICI response). Clinical trial landscape: multi-institutional (e.g., NCIC-CIRT, CHOP, VCS) testing combo regimens (e.g., TTx + ICI + RT). Notable: ADXS31-164 (Lm-LLO-HER2) in osteosarcoma (OS); anti-PDL1 + radiation in nasal carcinoma. Feline-specific data scarce; extrapolation from canine/human models common. Toxicity mgmt: TTx — proteinuria (VEGFRi), GI upset, neutropenia; ITx — immune-mediated hepatitis, colitis, hypothyroidism. Dose mod based on BSA, renal/hepatic function. Future: neoantigen vaccines, TIL therapy, bispecific antibodies, microbiome modulation to enhance ITx. Veterinary precision oncology (VPO) requires integration of genomics, immunophenotyping, and clinical data. Key barriers: cost, access, regulatory hurdles (extra-label use), limited validated assays. Collaborative networks (e.g., VETCAN, COAST) essential for data sharing and trial recruitment. Consensus protocols: Toceranib 2.75 mg/kg PO q48h (cMCT); Palladia + vinblastine in refractory CL; Oncept: 4 initial doses q2w, then q6mo. Monitoring: CBC, chemistry q2w x3mo, then qmo; urinalysis for proteinuria; thoracic rads q3mo; ctDNA q6w for MRD. Feline protocols: cautious chemo dosing (e.g., CCNU 50 mg/m² q3w for lymphoma); ITx largely off-label. Conclusion: TTx and ITx are transforming CFO, moving from empirical to precision-driven care. Success requires multidisciplinary approach: oncologist, pathologist, radiologist, molecular biologist. Education, biomarker validation, and accessible clinical trials are pivotal for advancement.