Precision Medicine in Myeloid Malignancies: Hype or Hope?

Banskota, Shristi Upadhyay; Khanal, Nabin; Marar, Rosalyn I; Dhakal, Prajwal; Bhatt, Vijaya Raj

doi:10.1007/s11899-022-00674-4

Cited by 5 publications

(3 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High heterogeneity in clinicobiological features such as genetic aberrations and clinical outcomes among patients with hematologic cancers has led to the realization that treatment strategies tailored to the individual patient are needed to improve disease management. Genomic strategies do to some extent guide treatment decisions [ 36 , 37 ], but further precision is required to avoid ineffective therapies [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Standardized assays to monitor drug sensitivity in hematologic cancers

Ayuda-Durán,

Hermansen,

Giliberto

et al. 2023

Cell Death Discov.

View full text Add to dashboard Cite

The principle of drug sensitivity testing is to expose cancer cells to a library of different drugs and measure its effects on cell viability. Recent technological advances, continuous approval of targeted therapies, and improved cell culture protocols have enhanced the precision and clinical relevance of such screens. Indeed, drug sensitivity testing has proven diagnostically valuable for patients with advanced hematologic cancers. However, different cell types behave differently in culture and therefore require optimized drug screening protocols to ensure that their ex vivo drug sensitivity accurately reflects in vivo drug responses. For example, primary chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) cells require unique microenvironmental stimuli to survive in culture, while this is less the case for acute myeloid leukemia (AML) cells. Here, we present our optimized and validated protocols for culturing and drug screening of primary cells from AML, CLL, and MM patients, and a generic protocol for cell line models. We also discuss drug library designs, reproducibility, and quality controls. We envision that these protocols may serve as community guidelines for the use and interpretation of assays to monitor drug sensitivity in hematologic cancers and thus contribute to standardization. The read-outs may provide insight into tumor biology, identify or confirm treatment resistance and sensitivity in real time, and ultimately guide clinical decision-making.

show abstract

Section: Discussionmentioning

confidence: 99%

Standardized assays to monitor drug sensitivity in hematologic cancers

Ayuda-Durán,

Hermansen,

Giliberto

et al. 2023

Cell Death Discov.

View full text Add to dashboard Cite

show abstract

“…This “7 + 3” regimen has yielded a 5-year survival of 20% to 35% in young patients and 10% in older patients ( 10 – 12 ). During the last 10 years, progress in the field has resulted in the creation of targeted agents tailored for specific mutations ( 1 , 13 ). Many of these agents have obtained approval from the Food and Drug Administration and are under investigation in ongoing clinical trials ( 13 – 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…During the last 10 years, progress in the field has resulted in the creation of targeted agents tailored for specific mutations ( 1 , 13 ). Many of these agents have obtained approval from the Food and Drug Administration and are under investigation in ongoing clinical trials ( 13 – 15 ). However, the effectiveness of these targeted drugs as monotherapies has been hindered by the development of drug resistance over time ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing

Zhou,

Chng

2024

Front. Oncol.

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a complex and heterogeneous group of aggressive hematopoietic stem cell disease. The presence of diverse and functionally distinct populations of leukemia cells within the same patient’s bone marrow or blood poses a significant challenge in diagnosing and treating AML. A substantial proportion of AML patients demonstrate resistance to induction chemotherapy and a grim prognosis upon relapse. The rapid advance in next generation sequencing technologies, such as single-cell RNA-sequencing (scRNA-seq), has revolutionized our understanding of AML pathogenesis by enabling high-resolution interrogation of the cellular heterogeneity in the AML ecosystem, and their transcriptional signatures at a single-cell level. New studies have successfully characterized the inextricably intertwined interactions among AML cells, immune cells and bone marrow microenvironment and their contributions to the AML development, therapeutic resistance and relapse. These findings have deepened and broadened our understanding the complexity and heterogeneity of AML, which are difficult to detect with bulk RNA-seq. This review encapsulates the burgeoning body of knowledge generated through scRNA-seq, providing the novel insights and discoveries it has unveiled in AML biology. Furthermore, we discuss the potential implications of scRNA-seq in therapeutic opportunities, focusing on immunotherapy. Finally, we highlight the current limitations and future direction of scRNA-seq in the field.

show abstract