For example, severe mutations may inhibit oxidative phosphorylation, increase ROS production and promote tumor cell proliferation, whereas milder mutations may permit tumors to adapt to new environments.
This may permit the tumor to become autonomous with respect to hormone sensitivity, allowing tumor progression.
Furthermore, hypoxia can induce genetic instability in cancer cells [ 28], and the steady proliferation of hypoxia-resistant cancer cell clones could foster the acquisition of additional mutations that may permit the tumor to re-establish a resistant vasculature (for example, through activation of alternative pro-angiogenic pathways and factor secretion).
These immunosuppressive agents may depress immune surveillance and permit tumor development [ 29, 34].
95 Of particular relevance, the c-Met pathway activates a program of cell dissociation, cell motility, and protease production, which can permit tumor cell invasion and cell scattering that may be linked to metastasis.
Thus, other mutations are probably required to permit tumor formation from non-ISCs.
In primary bone malignancies, a reliable, non-invasive method such as PET for assessing tumor viability may permit the oncologist and surgeon to individualize management of tumors that are aggressive, respond poorly, or arise in surgically challenging sites.
The more extensive infiltration of tumor sites by antigen-specific T cells may permit enhanced penetration of the tumor when compared to freely-injected nanoparticles, potentially augmenting therapeutic efficacy.
Alternatively, cellular plasticity and/or the tumor microenvironment may permit mature/differentiated cells to acquire a stem/progenitor phenotype [ 1- 6].
