LKB1 Identified as Potential Target in Ovarian Cancer

Trevor Shepherd, PhD

Trevor Shepherd, PhD

A team of scientists at Lawson Health Research Institute recently discovered that ovarian cancer spheroids activate a stress metabolism molecule, LKB1, which is crucial for the survival of ovarian cancer cells, according to one of the study’s authors, Trevor Shepherd, PhD.

LKB1 is as an enzyme that controls how a cell responds to a lack in nutrients, oxygen, and energy levels. Shepherd, a translational oncology scientist, explains that the enzyme is activated during starvation-like conditions, so that cells can survive until nutrients are once again available.

“It [LKB1] is not typically regarded as a cancer drug target, but our work shows that it may be an important molecule that ovarian cancer cells use to survive periods of stress and starvation-like conditions, while they are spreading to form new tumors,” said Shepherd, in an interview withTargeted Oncology.

Previous studies have shown that LKB1 could possibly be a tumor suppressor. In other words, it usually acts to block cancer in the early stages.LKB1mutations are present in many ovarian tumors, and they may allow early cancer to continue to grow.²“Our study demonstrates that LKB1 is actually still present in ovarian cancer cells, especially in late-stage or metastatic disease,” explained Shepherd.

He and his colleagues created a disease-relevant spheroid model of metastasis, in order to observe the function of the LKB1-AMP-activated protein kinase (AMPK) pathway in the ovarian cancer cells.¹When inside the body, ovarian cancer cells typically cluster together to form spheroids, which are sticky 3D structures that attach themselves to many different organs, like the uterus and liver. For months, or even years, they may lay dormant and go unnoticed, before they grow and become chemotherapy-resistant.²“Blocking LKB1 killed ovarian cancer cells in spheroids and this was even more effective when combined with chemotherapy drugs,” said Shepherd.

Shepherd and his team conducted the study in order to identify which molecule was in control of the process, as well as whether or not this molecule was significant in allowing ovarian cancer cells to survive and become chemotherapy resistant. They wanted to be able to show that LKB1 was activated in the cancer cell clusters and prove that it is possible to block LKB1 and kill the ovarian cancer cells.

As for future trials, Shepherd said, “Our current research focus is to develop agents that can target LKB1 and stress metabolism in multiple ways. These agents will be tested in ovarian tumor cells directly from patients and eventually in accurate preclinical animal models before translating into clinical trials.”

References:

1.     Peart, T, Valdes, YR, Correa, RJM et al. Intact LKB1 activity is required for survival of dormant ovarian cancer spheroids [published online June 5, 2015].Oncotarget.

2.     Lawson Health Research Institute. New research uncovers important molecule in ovarian cancer.https://www.lawsonresearch.com/archived_releases/2015/pdf/07_22_2015.pdf. July 23, 2015.