Cancer Metabolism and Microenvironment Program

Researchers reveal the internal signals cells use to maintain energy
For years scientists have tried to halt cancer by blocking nutrients from reaching tumor cells. But these attempts have been disappointing because cancer cells can adapt and create back up routes to source food to sustain their growth. One promising approach is to find and attack metabolic vulnerabilities within cells, which would deprive them of energy even in an abundance of nutrients and special tactics. In a recent study published in Developmental Cell, Dr. Brooke Emerling’s lab revealed that PI5P4Ks produce an active messenger that coordinates communications between peroxisomes and mitochondria—two organelles intimately involved in making and using fuel to support cellular growth. In the absence of the messenger, the interplay between the organelles breaks down, mitochondria become overworked, and cells starve and die. The scientists use sarcomas as a tumor model because PI5P4Ks are highly expressed in high grade sarcomas, and their expression correlates with patient survival. This research supports targeting PI5P4Ks as a cancer treatment strategy because it would deprive tumors of the one thing they can’t live without: energy.

Scientists shrink pancreatic tumors by starving stromal cells
Pancreatic cancer remains one of the deadliest cancers. Only one in ten people survive longer than five years, and its incidence is on the rise. Pancreatic tumors are surrounded by an unusually thick layer of stroma, or glue-like connective tissue that holds cells together. This stromal barrier makes it difficult for treatments to reach the tumor, and fuels tumor growth by providing the tumor with nutrients. In a recent study published in Cancer Discovery, Dr. Cosimo Commisso’s lab demonstrated for the first time that blocking “cell drinking,” or macropinocytosis, in the thick tissue surrounding a pancreatic tumor slowed tumor growth—providing more evidence that macropinocytosis is a driver of pancreatic cancer growth and is an important therapeutic target. The scientists deciphered the molecular signals that drive macropinocytosis in the stroma, providing new therapeutic avenues for pancreatic cancer researchers to explore. Macropinocytosis is a very important growth driver for many different cancer types and continued efforts to discover a drug that targets macropinocytosis may be the breakthrough needed to finally put an end to many deadly and devastating cancers.