The researches find that the immune system attack on the cells. Therefore The discovery resolves long-standing questions about how cyclophosphamide and other alkylating agents among the oldest and most widely used types of chemotherapy work, and suggests a novel way of sparking an immune system strike on certain cancers. Because Our results show that, at high doses, cyclophosphamide and other alkylating agents blur the line between chemotherapy and immunotherapy.
The immune system attack
These findings offer insights into how to switch on key immune system cells to augment existing therapies.” David Weinstock; MD, Study Senior Author; Dana-Farber Cyclophosphamide was just the eighth anti-cancer drug to enter standard therapy when it was approved by the U.S. Food and Drug Administration in 1954. It became a mainstay of cancer treatment after Burkitt and others used high doses to cure children with what’s now known as Burkitt lymphoma which had a 100% mortality rate at the time sometimes with only one dose.
Cyclophosphamide and other alkylating agents are now used at lower doses to treat many types of cancer; but including breast; ovarian; and pediatric cancers. Alkylating agents work by attaching chemical components called alkyl groups to cancer cells’ DNA; leading to breaks in the DNA molecule. Therefore The damage undermines the cells’ ability to duplicate their DNA and, ultimately, to divide.
The drugs’ effectiveness
Over the years, clues emerged that there’s more to the drugs’ effectiveness than damaging DNA. Researchers discovered, for example, that while high doses are much more effective against certain cancers than low doses, they inflict about the same amount of DNA damage, suggesting that something else comes into play at high doses. Sporadic data pointed to the immune system. Another clue came from pathology studies of Burkitt lymphoma tissue.
“Burkitt lymphoma and other high-grade lymphomas with rearrangements in the MYC gene have a ‘starry sky’ appearance under the microscope; with large numbers of macrophages [a type of immune system cell] dispersed among the lymphoma cells,” Weinstock remarked. In the new study, investigators focused on the effect of high doses of cyclophosphamide on macrophages cells that; under the right conditions, eat infected cells or cells in the process of dying.
In mouse models implanted with human lymphoma tissue; the researchers showed that high doses of the drug, but not normal doses, damaged tumor cells in a way that severely stressed the lymphoma cells. Therefore The stressed cells responded by secreting cytokines, substances that summon macrophages to eat the tumor cells. The researchers analyzed thousands of these macrophages to determine which genes were active, or expressed; in each of them.