Abstract:
For more than 100 years scientists have fanatically sought the fundamental origins of tumorigenesis, with the ultimate hope of discovering a cure. Indeed, these efforts have led to a significant understanding that multiple molecular and genetic aberrations, such as uncontrolled proliferation and the inhibition of apoptosis, contribute to the canonical characteristics of cancer. Despite these advances in our knowledge, a more thorough understanding, such as the precise cells, which are the targets of neoplastic transformation, especially in solid tumors, is currently lacking. An emerging hypothesis in the field is that cancer arises and is sustained from a rare subpopulation of tumor cells with characteristics that are highly similar to stem cells, such as the ability to self-renew and differentiate. In addition, more recent studies indicate that stem cell self-renewal pathways that are active primarily during embryonic development and adult tissue repair may be aberrantly activated in various cancers. It is well known that cancer stem cells have the characteristics of impaired apoptotic processes (Jagani and Khosravi, 2008). This phenomenon is most commonly associated with p53 mutations or loss of functional wild type p53 protein and the later has been demonstrated in retinoblastoma (RB) recently (Laurie et al., 2006). However, the recent discoveries of other p53 family proteins such as p63 and p73 added new insights and increases complexities to the analysis of p53 function. Reportedly, the truncated isoforms of p73 (and#61508;Np73) which is a putative antagonizer of p53 function (Wilhelm et al., 2010) is found to be overexpressed in several cancers (Nakagawa et al., 2002; Nekulova et al., 2010). Based on these evidences, the goal of maximizing tumor cell kill with conventional cancer therapy should also include specific cancer stem cell targets through pharmacological inhibition of self renewal pathways and provoke even a greater apoptotic response by activating the target protein (blocking and#61508;Np73 to restore p53 function
