New Compound Could Make Cancer Cells More Vulnerable

Increased knowledge of the mistaken activation process of certain cell-receptors allowed researchers in a recent study to make cancer cells more vulnerable to EGFR-driven cancers.

"We found that inhibiting an enzyme that adds the fatty acid palmitate onto proteins creates dependence by cancer cells on EGFR signaling for survival," said lead researcher Eric Witze, PhD.

Through using a small molecule called 2-bromo-palmitate (2BP), which inhibits palmitate-adding enzymes, the researchers hypothesize cancer cells could become more sensitive to EGFR inhibitors. According to the study published in Molecular Cell, palmitate is a common fatty acid that can allow proteins to transfer chemical signals from outside to inside the cell via the cell membrane.

EGFR can become hyperactivated by blocking palmitate and in EGFR-related cancers, EGFR becomes activated from blocking that process and cancer cells grow more slowly.

Researchers also noted that the EGFR inhibitor for lung cancer, genifitib, causes cancer cells to die. They added that the cells are addicted to the EGFR signal.

"It's as if a switch is stuck on. The cell loses control of the growth signal,” Dr Witze said. “If no palmitate is associated with EGFR, then it the cell loses control of this signal, and if the EGFR inhibitor is added, cells die."

The reversible modification of EGFR with palmitate is able to slow EGFR activation by pinning the tail of EGFR to the cell. The researchers believe that when the tail is not pinned to the membrane, the switch is stuck in the on position. The 2BP compound is toxic to most cells since it inhibits enzymes that use palmitate as a substrate.

"We need to find a compound specific for the palmitate-adding enzyme and or modify 2BP to make it more specific to decrease unwanted side effects." Dr Witze concluded.