Page 1272 - Clinical Small Animal Internal Medicine

1210 Section 11 Oncologic Disease

pyruvate by glycolytic enzymes. Under well‐oxygenated the multistep, coordinated foundation of the previously
VetBooks.ir conditions, pyruvate is oxidized in the tricarboxylic acid discussed hallmarks.
Experimental molecular oncology studies suggest that
cycle to form water and a substantial amount of ATP
(oxidative phosphorylation); however, under hypoxic
type is not simply the result of dysregulated signal trans-
conditions, lactate dehydrogenase A converts pyruvate the progression of a solid tumor to a metastatic pheno-
to lactate and generates very little ATP (glycolysis). duction pathways, but instead is achieved through a
It has been shown that glycolysis, under aerobic condi- stepwise selection process. The adaptation of popula-
tions, is particularly high in aggressive tumors when tions of neoplastic cells to their harsh microenvironment
compared with benign tumors and normal tissues. This facilitates cancer cell dissemination through the up‐ or
discovery of tumor‐specific, oxygen‐independent glyco- downregulation of critical metastasis‐associated genes,
lysis was labeled the Warburg effect. This peculiar meta- such as E‐/N‐cadherin for epithelial‐mesenchymal tran-
bolic preference of tumor cells drives a significantly sition (EMT), uPAR for degradation of the basement
inefficient breakdown of glucose for ATP and creates an membrane and extracellular matrix, HGF/MET for cell
acidic microenvironment through the build‐up of the motility, and VEGF for stromal interactions, intra/
byproduct lactic acid. extravasation, and angiogenesis. The systematic altera-
The increased dependence of cancer cells on the gly- tion of these phenotypic regulators allows cells to escape
colytic pathway provides a biochemical basis for the the hostile microenvironment of the primary tumor and
functional imaging technique positron emission tomog- colonize a secondary location.
raphy (PET). PET imaging has become increasingly The role of E‐cadherin in metastasis of veterinary can-
invaluable in human and veterinary oncology. Using the cer has been investigated. E‐cadherin is a transmem-
18
glucose analog fluorine‐18‐fluorodeoxyglucose ( FDG), brane glycoprotein involved in cell‐to‐cell adhesions of
the detection of glucose metabolism with PET is associ- two adjacent cells and is typically expressed by epithelial
ated with the presence of malignant tissue before ana- cells. Metastatic epithelial malignancies are associated
tomic evidence occurs. While traditional methods for with loss of E‐cadherin expression and connectivity with
determining response to therapy in veterinary oncology their neighboring cells; this leads to EMT, where epithe-
centers on anatomic changes in measurable target lial tumor cells obtain mesenchymal characteristics, as
lesions, 18 FDG‐PET combined with a CT scan can well as invasive and metastatic properties. In veterinary
be used as a sensitive marker of tumor response to anti- medicine, studies that have investigated E‐cadherin
cancer therapies via interrogation of cellular glucose expression have evaluated canine mammary carcinoma
metabolism. and anal sac gland adenocarcinoma for associations with
Positron emission tomography plays an important clinical malignancy.
role in the diagnosis, staging, image‐guided treatment Dissemination of primary tumor cells to a secondary
planning, and monitoring of malignant diseases. location may result in colonization of any number of
A recent preliminary study described the use of serial anatomic locations. One of the most common metastatic
18 FDG‐PET/CT to assess the response to toceranib sites is the first regional lymph node or nodes to which
therapy in canine cancer. Multiple types of canine tumors the lymphatics from the primary tumor drain; therefore,
have been evaluated for their avidity for FDG, including the disease status of what is known as this sentinel
mast cell tumor, lymphoma, mammary carcinoma, and lymph node (SNL) is important in cancer screening.
hemangiosarcoma. FDG‐PET has identified the involve- Lymphoscintigraphy, the injection of a radioactive tracer
ment of metastatic sites not detected on physical exami- at the tumor site to identify lymphatic drainage, and
nation and has been reported to provide more accurate intratumoral/peritumoral blue dye injection have been
disease detection for improved diagnosis, staging, and used to locate SNLs in veterinary oncology. The SNL can
restaging with treatment of companion animals with then be evaluated via histopathology for the presence of
cancer. metastatic disease. In veterinary practice, lymph nodes
are generally aspirated or biopsied if palpably enlarged;
however, since metastases occur in lymph nodes of nor-
mal clinical appearance and in lymph nodes other than
Activating Invasion and Metastasis those routinely assessed according to the anatomic loca-
tion of the primary tumor, this advanced technique for
The final hallmark to be reviewed is invasion and metas- metastasis identification has been recommended.
tasis, the processes of which are incredibly convoluted Reports describing SNL identification in veterinary
and intricate. The properties required to attain the phe- medicine include studies investigating canine head and
notype of an invasive and metastatic neoplasm involve neck tumors and mammary carcinoma.