바이오리더스

02

Inactivation of p53 in Tumors
Confers a Strong Selective Advantage
in the Carcinogenic Process

Eliminating p53 function may be a prerequisite
for tumor survival 1-3

Preclinical work has shown that the absence of p53
function is a continuous resquirement for the maintenance
of established tumors

Loss of functioning p53 promotes the
oncogenic phenotype 4

Cellular insults trigger phosphorylation of the
N-terminal domain of p53 leading to conformational
changes 5.6

Prevention of p53 degradation, prolonged molecular half-
life, accumulation of p53 at high levels

Cells without normal fuctioning p53 fail to recognize
and address cellular stressors/abnormalities, allowing
uncontrolled replication of affected cells 4

When p53 is functioning properly, oncogenic mutations
are not propagated, as DNA repair activities are intact
and cell cycling is tightly controlled 6

03

p53 is the Most Frequently Altered
Gene in Human Cancer

Somatic mutations in p53 have been seen in
several human tumors types-p53 multations or
deletions are observed in apporoximately 50%
of all solid tumors

Missense multations in p53 are frequent, and
can resu in gain of function changes that
enhance metastatic potential and invasiveness

In many tumor types, p53 mutations have
been associated with a poorer prognosis
with diminished overall survival and more
aggressive tumor behavior

p53 is not mutated in up to 50% of solid
tumors and is generally not mutated in
hematologic malignancies

In these tumors, wild-type p53(p53wt) is most likely
inactivated - inacyivation of p53 plays a critical role in
development and progression of the cancer5