Washington D.C.: A recent study has found that tobacco consumption leads to the formation of precancerous cells that fertilize cancer growth. There have been a lot of studies dedicated to cancer-related topics, exactly how this precancerous field influences cancer has been often overlooked. As part of the study, the researchers wanted to understand how these precancerous cells may impact neighboring cancer. The study explores this communication between precancerous and cancer cells in the context of an enzyme called PI3K.
The enzyme PI3K is activated in many or even most cancers, with some researchers considering PI3K over-activation an essential feature driving the disease. Attractively, PI3K is a "kinase" and the class of drugs known as kinase inhibitors has proven effective against a host of cancer types. Kinase inhibitors have been developed against PI3K as well, and by and large they do a lovely job of killing cancer cells in dishes. The ongoing question has been why PI3K inhibitors do not necessarily work in patients - what are cancer cells doing to resist this therapy that should kill them?
The current study offers an intriguing hint: "These cancer cell lines in culture are sensitive to PI3K inhibition, but when you put them next to precancerous cells, they become resistant," Young says. "These cancer cell lines in culture are sensitive to PI3K inhibition, but when you put them next to precancerous cells, they become resistant," said Christian Young, senior author of the study discussed in AACR Annual Meeting 2019.
To explore this observation, the team of researchers including first author Khoa Nguyen, grew head and neck cancer cells in the same dish as precancerous cells (called NOK cells), and then hit the cells, alone and together, with PI3K inhibitors. Cancer cells grown with NOK cells grew faster and resisted PI3K inhibition compared with cancer cells grown alone. When the researchers grew NOK cells alone, then removed the cells, and "fertilized" cancer cells with the culture medium in which NOK cells had grown, they saw similar cancer cell growth and PI3K inhibitor resistance.
Additionally, the NOK cells were stimulating cancer stem cell-like features in the recipient cancer cells. This means that in addition to resisting PI3K therapy, cancer cells that sit alongside precancerous cells may themselves become more dangerous, for example, more able to restart the disease.