With surgery and FidoCure® therapy, Callie is alive and well almost 20 months after her initial diagnosis of jejunal adenocarcinoma.
History and Initial Therapy
Callie Augur, a 10-year-old female spayed German Shepherd, was diagnosed with jejunal adenocarcinoma in May 2021. She was initially seen for a one week history of vomiting and anorexia. Her bowel movements began to decrease in frequency and quantity. Abdominal radiographs and a pneumocolonogram were performed. Both were concerning for segmental enteropathy and small intestinal obstruction.
She was then seen by the Surgery department, and a jejunal mass was excised. Biopsy was diagnostic for a transmural adenocarcinoma with a mitotic count of 12. Neoplastic cells did extend into the submucosa and smooth muscle through the serosa and into the attached mesentery. However, the mass was considered completely excised. Given the risk of disease progression, additional therapy was recommended.
Tissue from Callie’s intestinal tumor was sent for genomic (DNA) sequencing. Genomic analysis revealed alterations of K-RAS and P53.
K-RAS is a member of the RAS family of proteins primarily involved in regulating cell division. It belongs to a class of genes known as oncogenes, which play important roles in cell division, cell differentiation, and apoptosis. Activation of K-RAS or N-RAS oncogenic variants in canine tumors can activate the RAS/RAF/MAP kinase signaling pathway and downstream targets ERK1/2 and AKT. In vitro this is correlated with sensitivity to the MEK1/2 inhibitor Trametinib. Pre-clinical data suggest that one mechanism of adaptive resistance in RAS family mutant cancers exposed to MEK inhibition is enhanced activation of AKT/mTOR. Thus, a potential strategy to thwart this mechanism and sustain greater benefit may be combinatorial inhibition of MEK and mTORC1/2 targets.
TP53 encodes a protein called tumor protein p53 which has become one of the most well published tumor suppressor genes in human and canine cancer. This protein helps to regulate cell growth and damaged cells by controlling signals for pausing the cell cycle and cell death.
Based on the mutation profile, a combination of trametinib (MEK inhibitor) and rapamycin (mTOR) inhibitor were recommended. Callie was first started on trametinib at a 0.025 mg/kg/day dose in July 2021. She was tolerating that well, so rapamycin was started at a dose of 0.1 mg/kg/day in September 2021. Callie was rechecked every 4-6 weeks initially for bloodwork and did well with no concerns to report. She was restaged approximately every 3 months for thoracic radiographs and abdominal ultrasound.
Callie was last seen in July 2022 and was doing well at home. An ultrasound was performed, and there was no evidence of disease recurrence or metastasis. Given how well she has done on therapy, her rechecks were spread out to every 2 months.
With a combination of surgery and targeted therapy, Callie continues to do well almost 20 months following her initial diagnosis of jejunal adenocarcinoma.
Intestinal adenocarcinoma has a high metastatic rate, up to 70% in some studies. Reported median survival time with surgery alone is 10 months with some studies reporting 15 months for those with no evidence of metastatic disease at the time of diagnosis. The role of chemotherapy is relatively unknown for intestinal adenocarcinoma. Further research is needed to determine the role targeted therapy can play in delaying recurrence and/or metastasis.
What Callie’s Oncologist Says:
“Because we know that Callie's tumor displayed some concerning characteristics, including invasion into the submucosa, smooth muscle, through the serosa and attached mesentery. For this reason, I was concerned she was at high risk of metastasis since transcoelomic metastasis does occur with this tumor. Chemotherapy has not shown any survival benefit, so I recommended trying targeted therapies if her tumor exhibited mutations via Fidocure.”