Related Experiment Video

Updated: Jun 7, 2025

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

3.2K

BCL-2 inhibition in acute myeloid leukemia: resistance and combinations

Qi Zhang Tatarata1,2, Zhe Wang1, Marina Konopleva1,3

  • 1The Department of Leukemia, The University of Texas MD, Anderson Cancer Center, Houston, TX, USA.

Expert Review of Hematology
|November 18, 2024
PubMed
Abstract

Insights

Venetoclax offers new hope for acute myeloid leukemia (AML) but resistance limits its effectiveness. Understanding resistance mechanisms and exploring combination therapies are key to improving patient outcomes.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Venetoclax has transformed acute myeloid leukemia (AML) treatment.
  • Patient response to venetoclax varies, with many experiencing limited duration of response.

Purpose of the Study:

  • To elucidate mechanisms of venetoclax resistance in AML.
  • To explore therapeutic strategies to overcome venetoclax resistance.

Main Methods:

  • Review of intrinsic and acquired resistance mechanisms.
  • Analysis of BCL-2 family protein interactions, mitochondrial function, and microenvironment factors.

Main Results:

  • Intrinsic resistance linked to cell lineage and differentiation.
  • Acquired resistance involves alternative anti-apoptotic proteins, metabolic changes, and microenvironment interactions.

Conclusions:

  • Understanding resistance mechanisms is crucial for optimizing venetoclax-based AML therapy.
  • Targeted combination therapies show promise but require further clinical validation.
Keywords:
AMLVenetoclaxmetabolismmitochondriaresistancesignaling pathway

More Related Videos

Modeling Chemotherapy Resistant Leukemia In Vitro08:41

Modeling Chemotherapy Resistant Leukemia In Vitro

Published on: February 9, 2016

9.0K
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

14.8K

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.5K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K