A research team at the University of Arizona Cancer Center has discovered a new way of controlling blood vessel growth in tumors, a development that could make it easier to treat cancer patients.
“Tumors need blood vessels to deliver the oxygen and nutrients needed in order to grow,” said former graduate student Andrea Casillas. This process of new blood vessels forming is called angiogenesis, and it’s a way that cancer cells spread beyond the primary, or initial, tumor.
Assistant Professor Noel Warfel initiated this project, Casillas said, after studying the role of a pro-survival protein, Proviral Insert for the Moloney murine leukemia virus, or PIM1.
In his most recent research, Warfel — who specializes in cellular molecular medicine at the UA College of Medicine — identified how tumors with high levels of PIM1 were resistant to drugs that typically inhibit, or stunt, cancer growth. Tumors expressing PIM1, instead showed continued blood vessel growth in tumors.
Put simply: When you treat cancer cells with drugs that successfully block blood vessel expansion, it stops the blood flow and oxygen that’s necessary for growth. This leads to more PIM1, which restores blood flows and causes resistance to therapy.
This research was completed during Casillas’ time as a doctoral student in the UA’s Cancer Biology Graduate program. It has enabled researchers to use drugs that disrupt tumors’ ability to grow new blood vessels. Ultimately, this starves the tumor.
“We discovered that PIM1 is a new pathway that contributes to drug resistance. As a result, we found that combining a PIM1 inhibitor with a drug that blocks tumor vasculature, is really effective in preclinical models,” Warfel said. Vasculature is a network of blood vessels.
Researchers have found that drugs targeting the PIM1 enzyme can overcome resistance to such angiogenesis inhibitors, and work better at stopping tumor growth. Warfel hopes to take this research into clinical trials as a new means of cancer therapy.
“What we found expands our knowledge of how tumors maintain blood vessel growth and that expands the potential use of PIM1 inhibitors as a therapy in cancer and maybe even beyond,” Warfel said.
