There is a quickly growing arsenal of cancer treatments available for doctors to choose from and more patients than ever before now have therapies available which provide treatment responses.
However, cancer too often develops resistance to drug treatments resulting in tumor recurrence.
This is perhaps the greatest challenge faced by patients, doctors, and cancer researchers today.
Scientists have previously established that certain genetic mutations within cancer cells can emerge during treatment to drive drug resistance.
In some cases, there are additional drugs that target these mutations which doctors can choose from to provide further rounds of treatment.
However, resistance frequently emerges to each line of therapy and this “whack-a-mole” approach eventually runs out of treatment options.
An alternative approach could be to prevent resistance from emerging by pairing current cancer treatments with an “anti-resistance” drug.
However, due to a lack of understanding of how cancer cells develop these resistance mechanisms, there are no drug treatments available to block the emergence of resistance.
In an exciting new study, the first steps toward showing that an anti-resistance drug may be possible have now been taken. Scientists at the University of California San Diego have discovered that an enzyme called DFFB which normally promotes cell death is counterintuitively required for cancer cells to become drug resistant.
Specifically, scientists found that DFFB, which normally functions to destroy the DNA of a dying cell, instead promotes mutations and blocks growth suppressive signaling in surviving cancer cells to enable tumor regrowth during drug treatment.
“This flips our understanding of cancer cell death on its head,” said senior author Matthew J. Hangauer, Ph.D., Assistant Professor of Dermatology at UC San Diego School of Medicine and Moores Cancer Center member.
“Cancer cells which survive initial drug treatment experience sublethal cell death signaling which, instead of killing the cell, actually helps the cancer regrow. If we block this death signaling within these surviving cells, we can potentially stop tumors from relapsing during therapy.”
“Most research on resistance focuses on genetic mutations,” said first author August F. Williams, Ph.D., a postdoctoral fellow in the Hangauer lab at UC San Diego.
“Our work shows that non‑genetic regrowth mechanisms can come into play much earlier, and they may be targetable with drugs. This approach could help patients stay in remission longer and reduce the risk of recurrence.”
This finding reveals a possible way in which an anti-resistance drug may be developed: by creating a new drug which blocks DFFB or the pathway it is part of. While the translation of this discovery into a new therapy to help patients will likely take years, the prospect of the first anti-resistance drug is certain to motivate scientists to jump at this opportunity to change how cancer is treated and move beyond the current “whack-a-mole” paradigm.
The study was published in Nature Cell Biology and funded, in part, by grants from the Department of Defense, the National Institutes of Health and the American Cancer Society. Hangauer is a cofounder, consultant and research funding recipient of BridgeBio subsidiary.
