Targeting Cancer Metabolism and Cell Growth to Treat Pancreatic Cancer

Understanding cancer metabolism and cancer cell growth could lead to new ways to treat pancreatic cancer.

Researchers at New York University (NYU) School of Medicine may have figured out how ravenous pancreatic tumor cells feed themselves, according to a study published in the prestigious scientific journal Nature. Identifying this nutritional mechanism could open new doors for cancer treatments.

In many cancers, including pancreatic, a mutated version of a protein called Ras helps drive tumor cell growth and cancer progression. These Ras-mutated cells need extra nutrients to finance their accelerated growth, but until recently scientists didn’t fully understand how they met their food requirements.

In the Nature study, led by Cosimo Commisso, a postdoctoral fellow in the Department of Biochemistry and Molecular Pharmacology at NYU School of Medicine, the researchers showed that cancer cells with a specific Ras mutation known as KRAS use a feeding method called macropinocytosis. This mechanism allows the cells to devour an abundant natural protein called albumin. The tumor cells then dismantle the albumin for amino acids, which are necessary for the cancer cells’ growth.

During macropinocytosis, a large fluid-filled sac called a macropinosome is pinched off from the cell membrane and brought to the interior of the cell, where its contents, including nutrients, can be used by the cell machinery.

Commisso and colleagues found that pancreatic cancer cells had more macropinosomes than did normal cells. And pancreatic tumors in mice stopped growing and sometimes even shrank when the researchers used a chemical to block macropinocytosis. “A big mystery is how certain tumors meet their excessive nutrient demands,” Dr. Commisso said. “We believe they accomplish this by macropinocytosis.”

The findings suggest that the process of macropinocytosis is necessary for KRAS cancer cells to thrive. If so, blocking the process may offer a new way to kill off cancer cells. “This work offers up a completely different way to target cancer metabolism,” said Dafna Bar-Sagi, PhD, senior vice president and vice dean for Science, chief scientific officer and professor, Department of Biochemistry and Molecular Pharmacology, at NYU Langone Medical Center, who was lead investigator on the study. “It’s exciting to think that we can cause the demise of some cancer cells simply by blocking this nutrient delivery process.”

Alternatively, researchers might leverage this uptake mechanism as a way to get tumor cells to take up anti-cancer drugs, by fooling them into devouring chemotherapies or novel treatments along with albumin.