In biomedical research there exists a certain consensus among cancer researchers that genetic instability or ''mutability'' is a major critical force of cancer progression, but it is not the only one to consider. It is clear that the mutational damage of key genes (like TP53, TERT, BRCA1, RB1, etc.), and the collective damage inflicted on key DNA repair mechanisms (like Nucleotide-excision repair and Base-excision repair) collaborate for an increasing acceleration of the number of genomic changes. Sub-microscopic alterations of the genome accumulate in cancer progression in an irreversible way and ''are compounded by the widespread scrambling of the chromosome structure, and thus the karyotype, found in cells from the great majority of solid tumours'' [599] . In Weinberg's own words [599] : ''we learned that this chromosomal chaos also contributes this progression forward''.