Latest News in MF Cancer Research
Myelofibrosis (MF) is a rare type of bone marrow cancer that disrupts normal production of blood cells. MF usually develops slowly, and initially a patient may not notice any symptoms, but over time patients begin to experience fatigue as a result of anemia (low red blood cell counts), pain from an enlarged spleen, fever, bone pain, and easy bruising and swelling.
Patients in more advanced stages of the disease require aggressive treatments which have mainly focused on relieving symptoms. A common treatment for MF is allogeneic stem cell transplantation, but unfortunately this is not an option for most MF patients because it is risky for older adults. Because of this, clinical trials may be the best treatment choice for some MF patients.
Hematoxylin compounds in targeting CALR mutant cancer cells
Back in 2013, it was discovered that certain mutations of a gene called calreticulin, known as CALR, were often found in patients with MF. Since then, researchers have been able to identify and understand how the mutated version of this gene functions. This led them to understand that CALR works by interacting with a certain receptor that has to do with platelet formation.
In 2020, researchers at the research group of Robert Kralovics at CeMM were looking for ways to stop this interaction and stop the growth of CALR mutated cells. They found a certain group of chemicals that was able to selectively kill mutated CALR cells while leaving healthy cells unaffected. The chemical that worked most notably was hematoxylin, which is a chemical that has been used as a dye for staining cells in laboratory work in the past.
This study shows the potential that CALR inhibitor therapy has for MF patients, and especially primary myelofibrosis (PMF) patients. Kralovics said that the treatment of patients with PMF has had poor clinical outcomes up until this point, and since about a third of PMF patients have a CALR mutation, this new therapeutic approach could benefit them in particular.
Momelotinib as a treatment for MF
There have been studies in the past that used JAK inhibitors (a type of medication that stops the activity of a certain gene called JAK that has to do with cell growth) to treat MF. However, while these treatments did help with the enlarged spleen and some other symptoms of MF patients, they worsened other symptoms like anemia and thrombocytopenia (low platelet levels).
A new treatment has been developed using a drug called momelotinib. This drug is similar to the older treatments as it is a JAK inhibitor, but it also inhibits another gene called ACVR1. Inhibiting this gene causes a decrease in the levels of hepcidin, a hormone that controls iron balance in the body, which can potentially improve anemia in MF patients.
Results from clinical trials involving momelotinib have shown promising results, and the drug is currently being investigated in a phase 3 study. The several studies that have already been completed show that momelotinib has potential as a new treatment option for MF patients.