BY AMBER SMITH
Cancer researchers for decades have focused their microscopes on the tissue where cancer is discovered, be it the lung, the breast, the skin or elsewhere.
“Now we are learning it’s not so much where the cancer comes from, but the mutations that cause each individual to develop cancer and allow that cancer to progress,” said Adam Blanden, a fourth-year MD/PhD student in his second year working in the lab of Stewart Loh, PhD, a professor of biochemistry and molecular biology at Upstate Medical University.
Research underway in Loh’s lab focuses on mutations of a gene called p53, on chromosome 17, which is implicated in about half of human cancers — regardless of the tissue in which the cancer is found.
The gene is a tumor suppressor, meaning it is supposed to stop the formation of tumors. But when the gene mutates, it does the opposite, playing a role in a series of complex molecular events that lead to tumor formation.
“There are lots of ways p53 can go wrong, and one way is the loss of zinc,” Blanden said.
His work involves restoring proper zinc binding to several zinc-impaired mutations in p53, including the most common mutation that leads to cancers.
“This is a fundamentally new way to approach the problem,” he said. “We’re trying to change the environment of the cell so that even if p53 is defective, it can still function. It’s a complete end-around.”
The traditional approach, Blanden explained, has been to search for molecular compounds that restore the activity of the mutated p53 by binding to it and “fixing” it. Those attempts have been unsuccessful.
Loh and his collaborators at the Rutgers Cancer Institute of New Jersey have discovered a new class of experimental cancer drugs that can reactivate mutant p53 by shuttling zinc ions into cells. Their work appears most recently in the May issue of the journal Molecular Pharmacology, the July issue of the journal Drug Discovery Today and the August issue of the journal Oncotarget.
A safe, effective treatment is likely at least a decade away, but Blanden imagines it could work like this:
A patient receives a cancer diagnosis. Genetic sequencing is done to determine if the patient’s p53 gene is mutated, and if so, if the mutant p53 is one of numerous types that can be reactivated by restoring zinc binding. Treatment would then likely consist of zinc in combination with a drug optimized for that particular p53 mutant.
This article appears in the fall 2015 issue of Cancer Care magazine.