New breakthrough by a team led by eminent oncologist Loren Walensky brings new hope for future cancer treatments – and Longevity.
Everyone needs a way to get rid of unwanted waste, whether we are talking about the human body or our household rubbish. It turns out that cancer cells are no different. They too need to rid themselves of waste to ensure their continued survival.
Longevity.Technology: Advancing age is the most important risk factor for cancer overall, with a quarter of new cancer cases diagnosed in people aged 65 to 74 [1]. Now, a research team has come up with a new way to turn cancer cells against themselves [2]. By jamming cancer cells’ “garbage disposal” mechanism, scientists working from the laboratory of Loren Walensky, MD, PhD, have discovered a new way to make cancer cells essentially self destruct.
The researchers at the Dana-Farber Cancer Institute have created a novel peptide molecule that binds to the ubiquitin-proteasome system (UPS) in cancer cells. The UPS is a necessary survival mechanism for cancer cells, enabling them to get rid of proteins which could otherwise build up, ultimately causing toxic stress which could kill off the cells.
It is not the first time that scientists have exploited this system. In recent years, drugs such as bortezomib have been developed which inhibit the protein disposal system in myeloma cells.
“This stapled peptide could itself be developed as a therapeutic, or it could serve as a blueprint for developing small molecule drugs based on the mechanism we identified for stapled peptide blockade of UPS. We believe this is an exciting new strategy for cancer therapy.”
Now, Walensky, along with colleagues including first author Ann Cathcart, PhD, have built on this earlier research by creating a compound which targets a different part of the UPS than that sought out by bortezomib. While bortezomib and other drugs stop the UPS process at its final step, Walensky’s team has come up with a way to block the UPS process at the very first step.
The team has developed a peptide molecule which blocks the first critical step of the protein disposal process. The compound they have created fits into a groove in an essential UPS protein known as E1, which means that E1 and another UPS enzyme, E2, can no longer interact.
Walensky and his team are now hopeful that this groove could be a potential drug target site, which could lead to the development of further cancer drugs which target the UPS. While Walensky has been renowned for his work in the field of paediatric oncology, this breakthrough could also potentially be significant for a wide range of cancers, including those which predominantly affect an older population.
In addition, understanding more about the role proteins take in determining and controlling cell growth, how that can be slowed or accelerated and how the protein disposal process can be manipulated to cause or prevent cell death is important for Longevity. This research could contribute to extending healthspan and lifespan on a cellular level.
“Cancer cells make many more proteins, including defective ones, to sustain their excessive growth compared to normal cells,” said Walensky. “That is why blocking UPS system preferentially affects cancer cells more than normal cells, producing a ‘therapeutic window’ in which a carefully calculated dose of a UPS-blocking drug can kill cancer cells but spare normal cells.”
“This stapled peptide could itself be developed as a therapeutic, or it could serve as a blueprint for developing small molecule drugs based on the mechanism we identified for stapled peptide blockade of UPS. We believe this is an exciting new strategy for cancer therapy.”
[1] https://www.cancer.gov/about-cancer/causes-prevention/risk/age
[2] https://bit.ly/3jrAZKU
