In the ongoing battle against cancer, researchers at the National University of Singapore (NUS) have made a groundbreaking discovery shedding light on drug resistance in patients with relapsed acute myeloid leukemia (AML). Their findings, published in the journal Blood Cancer Discovery, offer new insights into the mechanisms driving resistance and provide hope for the development of more effective treatments.
Treating cancer patients upon relapse presents significant challenges, as they often develop resistance not only to the initial treatment but also to multiple other drugs—a phenomenon known as acquired multi-drug resistance. Despite decades of research, the underlying mechanisms behind this resistance have remained elusive.
Led by Assistant Professor Shruti Bhatt, the research team identified a common mechanism underlying drug resistance in relapsed AML patients: the mitochondria. Through in vivo models and comprehensive analysis, they discovered a reduction in mitochondrial apoptotic priming—a key indicator of programmed cell death—in drug-resistant AML cells. This finding suggests that compromised mitochondrial function is a fundamental driver of multi-drug resistance, transcending the type of therapy and genetic background of the tumor.
To combat drug resistance, the researchers turned to dynamic BH3 profiling (DBP), a technique that measures mitochondrial apoptotic signaling in response to drug treatment. By applying DBP across a range of AML models, they successfully identified drugs capable of overcoming resistance with remarkable accuracy. This approach offers a promising strategy for predicting the efficacy of new therapies and developing targeted treatment regimens tailored to individual patients.
Building on their findings, the research team is now focusing on identifying molecular determinants responsible for reduced mitochondrial priming at the minimal residual disease stage. By conducting single-cell lineage tracing experiments, they hope to uncover new insights into the mechanisms of drug resistance and develop innovative therapeutic strategies.
The discovery of mitochondrial dysfunction as a key driver of drug resistance in relapsed AML represents a significant advancement in cancer research. Through their innovative approach, the researchers at NUS have not only deepened our understanding of drug resistance mechanisms but also opened new avenues for the development of more effective therapies. As they continue to unravel the mysteries of mitochondria and cancer therapy resistance, their work holds the promise of improving outcomes for patients battling this devastating disease.
Publish Time: 12:50
Publish Date: 2024-03-27
