Osteosarcoma (OS) is a rare, metastatic, human adolescent cancer that also occurs in pet dogs. To define the genomic underpinnings of canine OS, we performed multi-platform analysis of OS tumors from 59 dogs, including whole genome sequencing ( n = 24) and whole exome sequencing (WES; n = 13) of primary tumors and matched normal tissue, WES ( n = 10) of matched primary/metastatic/normal samples and RNA sequencing ( n = 54) of primary tumors. We found that canine OS recapitulates features of human OS including low point mutation burden (median 1.98 per Mb) with a trend towards higher burden in metastases, high structural complexity, frequent TP53 (71%), PI3K pathway (37%), and MAPK pathway mutations (17%), and low expression of immune-associated genes. We also identified novel features of canine OS including putatively inactivating somatic SETD2 (42%) and DMD (50%) aberrations. These findings set the stage for understanding OS development in dogs and humans, and establish genomic contexts for future comparative analyses.

Spontaneous cancers in client-owned dogs closely recapitulate their human counterparts with respect to clinical presentation, histological features, molecular profiles, and response and resistance to therapy, as well as the evolution of drug-resistant metastases. In several instances the incorporation of dogs with cancer into the preclinical development path of cancer therapeutics has influenced outcome by helping to establish pharmacokinetic/pharmacodynamics relationships, dose/regimen, expected clinical toxicities, and ultimately the potential for biologic activity. As our understanding regarding the molecular drivers of canine cancers has improved, unique opportunities have emerged to leverage this spontaneous model to better guide cancer drug development so that therapies likely to fail are eliminated earlier and therapies with true potential are optimized prior to human studies. Both pets and people benefit from this approach, as it provides dogs with access to cutting-edge cancer treatments and helps to insure that people are given treatments more likely to succeed.

RAD001 10 mg/day was well tolerated, showing modest clinical activity in pretreated NSCLC. Evaluation of RAD001 plus standard therapy for metastatic NSCLC continues.

The objective of this retrospective study was to report the outcome of treatment of canine oral fibrosarcomas (FSA) in relation to median survival and progression-free survival (PFS), and to report whether grade was prognostic in relation to median survival. Sixty-five dogs with oral FSA presented to the WSU VTH between June 1998 and March 2010. Significant predictors of median survival were location (P = 0.0099), tumour size or oral stage (P = 0.0312), type of surgery (P = 0.0182), margins (P = 0.0329) and grade (P = 0.0251). Significant predictors of PFS were location (P = 0.0177), and radiation protocol (P = 0.0343). A combination of surgery and radiation was the strongest predictor of prolonged median survival (P = 0.0183) and PFS (P = 0.0263) at 505 and 301 days, respectively. Treatment of canine oral FSA with a combination of surgery and radiation therapy provided the longest median survivals.