New Drug Combo Targets Myeloma Growth

Uppsala University Study Uncovers Promising Dual-Action Therapy for Blood Cancer

A significant stride in combating the persistent blood cancer, multiple myeloma, has been made by researchers at Uppsala University. Their recent preclinical findings reveal a dual-drug approach that effectively curbs tumor expansion and triggers cancer cell demise.

Targeting Epigenetic Regulators

Multiple myeloma, a challenging bone marrow malignancy, remains incurable despite advancements in treatment. The disease is marked by significant genetic and clinical variability, often seen as rapid proliferation of antibody-producing immune cells. Crucial to its progression are epigenetic alterations—changes to the genome not caused by direct mutations, which influence gene activity and cell growth.

The Uppsala University team zeroed in on two proteins, G9a and DNMTs, known to play a role in multiple myeloma’s development and linked to poorer patient prognoses. Inhibiting these specific proteins in laboratory settings, using cultivated cancer cells and actual patient samples, yielded substantial reductions in cell viability and promoted programmed cell death, also known as apoptosis.

“The proteins we focused on are called G9a and DNMTs. We treated cultivated both cancer cells and primary patient samples with two different drug substances that inhibit these proteins. We found that this significantly reduced cell viability and induced apoptosis – programmed cell death. The combination therapy also led to a notable decrease in the levels of critical oncoproteins.”

—Patrick Nylund, Postdoctoral Researcher, Department of Immunology, Genetics and Pathology

Synergistic Effect in Preclinical Models

Further investigations using a mouse model demonstrated a synergistic impact when both G9a and DNMT inhibitors were administered together. This combined treatment resulted in greater tumor growth reduction than would be expected from the sum of individual treatments.

This dual inhibition strategy also activated tumor suppressor genes and a range of genes associated with apoptosis, amplifying the anti-tumor effects observed. The research, a collaboration involving institutions in Sweden, Belgium, and Spain, provides the first preclinical backing for simultaneously targeting both DNMTs and G9a as a therapeutic avenue.

This breakthrough is particularly encouraging given that multiple myeloma affects approximately 30,000 individuals in the United States annually, with about 12,600 new cases expected in 2024, according to the American Cancer Society (American Cancer Society 2024).

Professor Helena Jernberg Wiklund, who spearheaded the study, noted, “Our research offers important insights into how G9a and DNMTs cooperate to mediate gene silencing through epigenetic mechanisms in multiple myeloma. This study is the first preclinical evidence to support the therapeutic potential of simultaneously targeting both DNMTs and G9a. This is exciting for the development of new therapeutic strategies for this challenging disease.”