Distant metastasis from HNSCC can be either synchronous or asynchronous, the former
of which is the situation that the metastatic foci is found by the time the primary
cancer is diagnosed or shortly after that, and the latter of which is the metastatic
lesions is confirmed thereafter. It is believed that once the distant metastasis occurs,
there is almost no cure, no matter the metastasis is concurrent or not. For HNSCC,
the metastatic nature is closely related to some important clininopathologic factors
of tumors, most important of which are primary tumor site, depth of invasion, numbers
of involved neck levels and extracapsular spread of the neck nodes. Many components
of tumor microenvironment, such as hypoxia, also contribute to the pathogenesis of
distant metastasis. Targeting hypoxia can help to prevent malignant transformation
and progression of cancers. One effective way to target hypoxia is to block hypoxia-inducible
factor (HIF) expression, with subsequent inhibition of its downstream signaling cascades.
Cancer stem cells (CSC), also known as tumor initiating cells, are a specific and
small cell population in cancers, exhibiting strong abilities of invasion, migration
and metastasis. Targeting CSCs resides on identifying specific marker expressed on
cell surface and blocking key molecules that execute their aggressive behaviors. A
good example for targeting specific signaling molecules is to inactivate phorsphorylated
STAT3, a key molecule closely related to cancer progression. Targeting these checkpoints
can be realized by administration of specific chemicals or by genetic manipulations
via molecular biological methods.
