Overview

Researchers at Duke University have shown that blocking ⁢an enzyme⁤ involved in⁣ iron regulation not only kills multiple myeloma ⁣cancer cells, but also increases the effectiveness of current therapies against the disease.

The research appeared September 12, 2023, in the ‍journal Blood. Read the full study in Blood.

understanding ⁢Multiple Myeloma

Multiple myeloma (MM) is an incurable cancer of plasma cells, a type of white blood cell responsible for producing antibodies to fight infection. In MM, these cells proliferate uncontrollably in the bone marrow, crowding out healthy blood-forming cells⁤ and ⁣producing abnormal antibodies.

This buildup leads to a cascade of health problems, including a⁣ weakened immune system, kidney damage, and painful bone disease. According to the⁣ American Cancer Society,multiple myeloma accounts for approximately 1.8% of all cancer diagnoses in the United States.⁣ American Cancer Society Key Statistics. While treatments exist to manage the disease, relapse and the advancement of drug ⁢resistance are meaningful challenges.

In 2023, an estimated 35,730 new cases of multiple myeloma will be diagnosed in the United States. American Cancer Society Key Statistics

The Role of ⁤Iron and Ferroptosis

Researchers have observed a connection between multiple myeloma and the suppression of ferroptosis, a form of regulated cell death. Ferroptosis is triggered by the⁤ accumulation‍ of excess iron,leading to oxidative damage‍ to cell membranes ⁣and ultimately,cell breakdown.

Normally, this ⁣process would eliminate damaged or cancerous cells. ‍However, myeloma‍ cells appear to adapt and ⁤resist ⁣ferroptosis, allowing them to survive and proliferate despite high iron levels. “Cancer cells live like there is no ⁣tomorrow,” said‍ Mikhail Nikiforov, professor of pathology and biomedical engineering at Duke. “They ⁢accumulate iron at levels that would normally⁢ be toxic and tear cells‍ apart, but that wasn’t what we⁣ observed. Instead, these cancer cells ⁣adapted to resist the type of cell death triggered by iron overload, and the mechanism…”

The Duke University research ⁢focused on the enzyme FTH1, which controls iron levels within cells. ‍ By blocking FTH1, researchers where able⁤ to disrupt iron regulation, ⁣triggering ferroptosis and killing myeloma cells.

Key Findings of the Duke Study

the study demonstrated that inhibiting FTH1 not only directly killed multiple myeloma cells but⁤ also considerably enhanced the effectiveness of existing therapies, such as bortezomib and dexamethasone. ‍ This suggests that targeting FTH1 could be ⁤a valuable strategy for overcoming drug resistance in ⁣multiple myeloma.

Specifically, the⁤ researchers found that blocking FTH1 increased the production of reactive ‍oxygen species (ROS) within myeloma cells, leading to oxidative stress and cell ⁤death.‍ This effect was ⁢especially pronounced in myeloma cells that were resistant to conventional treatments.

The research ⁤team utilized both in ⁣vitro (laboratory) ⁤and in vivo ⁣(animal model) experiments to validate⁤ their findings. The ⁤results showed a significant reduction in tumor ‍growth in mice treated with FTH1‍ inhibitors, both as a standalone therapy and⁣ in combination with standard treatments.