20911.2 Tumor Heterogeneity and Tumor Niche
The tumor “onco-genotype” evolves gradually over time due to inherent genomic
instability that makes nearly every tumor cell population unique and increases the
clinical challenges for effective treatment as it also differs among patients. Many
reports claim that tumor mass often show significant intratumor heterogeneity
encompassing various discernable phenotypic features including cellular morphol-
ogy, genetic heterogeneity, metabotypes, proliferative, angiogenic, immunogenic,
and metastatic potential. Such phenotypic and functional heterogeneity among the
cells within the same tumor occur as a consequence of integration of both genetic
and non-genetic influences including genetic alteration, environmental variations
and reversible changes in cell properties (Marusyk et al. 2012 ; Meacham and
Morrison 2013 ). The pedigrees of intratumoral heterogeneity are extremely dis-
puted and various cellular mechanisms are hypothesized to rationalize the diversity
within a tumor. The two major frameworks that explain the intratumor phenotypic
heterogeneity are “Clonal Evolution Model” or “Stochastic Model” and “Cancer
Stem Cell (CSC) Model” or “Hierarchical Model”. The clonal evolution model was
Fig. 11.1 Therapeutic relevance of oral cancer stem cells. Conventional or traditional therapy
targets only bulk cells of oral cancer sparing the cancer stem cell population by virtue of abrupt
developmental signaling, altered drug metabolism, niche remodeling and epigenetic reprogram-
ming which subsequent in survival and maintenance of oral CSCs post-therapy followed to thera-
peutic resistance and recurrence of oral cavity cancers. Combinatorial therapy of targeting both
CSCs and their microenvironmental link ups will be more effective in tumor remission
11 Oral Cancer Stem Cells Microenvironment