It is common for cancer cells to find some way to disarm p53, also known as "guardian of the genome" due to its action in preventing defective cells from dividing. "The critical importance of the protective function of p53 is underscored by the diversity of molecular strategies employed by cancer cells to subvert p53 activity, such as overexpression of antagonistic proteins like HDM2 and HDMX," explains senior study author Dr. Loren D. Walensky from Harvard Medical School. "Restoration of p53 activity remains an important goal in the quest for more effective cancer therapeutics."
Previous work demonstrated that selective inhibition of HDM2 restored p53 function in cancer cells. However, these results were often compromised by expression of HDMX. In an earlier study, Dr. Walensky and colleagues described the generation of "stapled" peptides designed to resemble the section of p53 that interacts with HDM2. When biochemical and structural studies revealed that HDM2 and HDMX engage the same region of p53, the researchers examined whether the most effective engineered HDM2 inhibitor (SAH-p53-8) could also interfere with HDMX and how this interaction might influence the p53 activity.
The SAH-p53-8 compound was even more effective at targeting HDMX and effectively blocked formation of the inhibitory p53-HDMX complex, thereby restoring the p53 pathway and reducing tumor cell viability. Importantly, when SAH-p53-8 was delivered intravenously to mice with HDMX-expressing cancer, p53 activity was increased and tumor growth was suppressed.
"We found that targeting HDMX overcame HDMX-mediated p53 suppression and resistance to selective HDM2 inhibition, while dual targeting of HDM2 and HDMX maximized therapeutic reactivation of the p53 tumor suppressor pathway in cancers that express both protein antagonists and retain functional p53," concludes Dr. Walensky. "Importantly, monitoring cellular levels of p53-HDMX complex may be useful for predicting cancer cell susceptibility to HDMX inhibition and determining the efficacy of HDM2 inhibitor-mediated p53 restoration, which forms the basis for enhancing the therapeutic impact of dual HDM2/HDMX targeting in resistant cancers."


It often occurs that cancer cells will combat the natural protection against it within the body. This protector is called p53, a.k.a. the “guardian of the g-nome.” A new compound called SAH-p53-8 has been used in experimentally combating HDMX protein which plays a role in cancer’s ability to get passed our p53. It’s hopeful that this is the first step to a p53 restoring treatment.
This is an interesting find for the medical community that I would love to here more of. Though it’s far from a cure to cancer, it is a start in the right direction to assisting our bodies in naturally combating the condition more easily. It would very ground breaking if we were only required to go through a bare minimum of cancer treatment because our bodies could do the rest by itself.