Uncontrolled inflammation may be the key to tackling resistant cancers – Salud y Medicina

2023-05-18 08:26:59

For the first time, it has been possible to discover the molecular circuit through which mutations in a gene, STK11, cause inflammation to get out of control.

Scientists from the Van Andel Institute (USA) have identified how a specific genetic mutation triggers an inflammatory cascade that can drive the development of cancers resistant to treatment.

The new findings, published in ‘Molecular Cell’, reveal for the first time the molecular circuitry by which mutations in the STK11 gene cause inflammation to run amok. The resulting chemical firestorm damages healthy cells and can allow cancer to develop. Tumors that lose the STK11 gene are difficult to treat because they resist traditional chemotherapy and many of the newer immunotherapies, according to these scientists.

“Understanding how and why this mutation leads to cancer is a critical step in developing improved treatments.“, indicated the prof. Russell Jones, Chairman of VAI’s Department of Metabolism and Nutritional Programming and corresponding author of the study. “Our study identifies important features of these cancers and suggests that targeting inflammation may make these tumors more responsive to treatment.”

key interruptions

STK11 mutations occur when the instructions encoded by the gene are disrupted. This causes the gene to produce insufficient levels of the LKB1 protein, a tumor suppressor that keeps cell growth in check. Loss of LKB1 derails critical cellular checks and balances and allows cancer cells to grow unhindered.

Loss of LKB1 is among the most common gene mutations in human cancer, especially in refractory lung cancer and in pancreatic and cervical cancers. He is also the lead actor in the rare disease Peutz-Jehgers Syndrome. People with Peutz-Jehgers syndrome develop polyps in the digestive tract and have a significantly increased risk of cancer.

Although LKB1 has long been linked to cancer, exactly how it worked to promote tumor growth was unclear. Previous research by Jones and his team hinted that LKB1’s control of inflammation may be to blame, but the mechanism was unknown. Recent findings shed more light on the process.

LKB1 works in part by regulating inflammation, which is a normal part of the body’s defense mechanisms against injury and infection. When LKB1 is lost, it triggers an epigenetic change in cells, affecting the way the instructions encoded in the DNA are acted on. This results in rampant inflammation that damages healthy cells and can push them closer to malignancy.

“It’s a perfect storm of problems for which we now have possible solutions,” indicated, for her part, prof. Shelby Compton, of the Van Andel Institute Graduate School. “In addition to cancer, we are hopeful that this work will serve as the basis for new therapeutic strategies for Peutz-Jehgers syndrome, which has few treatments and no cure.” added.

The next step is to develop strategies to target inflammation in LKB1-associated cancers. The team also plans to continue exploring LKB1 in Peutz-Jehgers syndrome with the goal of working on new and much-needed therapies for people with this condition. J.S.LL./M.T.T. (SyM)