Cancer Biology: Learning to Sensitize ‘Tenacious’ Tumour Cells

Researchers at OCI have discovered a new pathway that tumours use to survive during conditions of hypoxia (deprivation of oxygen) and become more aggressive and resistant to current cancer treatment strategies. By strategically manipulating this pathway, researchers believe that these once ‘treatment resistant’ tumours could become sensitive to radiation or chemotherapy.

As explained by study lead Dr. Bradly Wouters, “It is extremely important to understand how to tumours are able to adapt to metabolic stresses like hypoxia because these mechanisms lead to more aggressive cancers that are difficult to treat effectively.”

With colleagues from the Ontario Institute for Cancer Research and Europe, the team conducted a series of molecular investigations in several human cancers to show that the unfolded protein response (UPR) mechanism protects human tumour cells by enhancing the activity of MAP1LC3B and ATG5 genes. This enables the tumour cells to carry out a form of self-eating or autophagy, thus allowing them to survive under nutrient and oxygen poor conditions. Ultimately, this activity promotes human tumour cell survival and contributes to tumour cell treatment resistance.

“When we disabled this adaptive mechanism through genetic or pharmacological agents, previously resistant tumours became less hypoxic and more sensitive to irradiation,” comments Dr. Wouters. “Our future studies will continue to target the UPR as a mediator of hypoxic tumour environments to make resistant hypoxic tumour cells sensitive to treatment.”

Find this story on the web at: www@uhnresearch.ca