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Rational combination strategies to enhance venetoclax activity and overcome resistance in hematologic malignancies

Steven Grant1,2,3

  • 1a Department of Medicine, Biochemistry, Pharmacology, and Human and Molecular Genetics , Virginia Commonwealth University , Richmond , VA , USA.

Leukemia & Lymphoma
|August 26, 2017
PubMed

Insights

Venetoclax shows promise in blood cancers but resistance is an issue. Combining it with other therapies, especially those targeting Mcl-1, may overcome resistance and improve outcomes.

Area of Science:

  • Oncology
  • Hematology
  • Molecular Biology

Background:

  • Venetoclax (ABT-199) is a targeted therapy effective against certain leukemias and lymphomas.
  • Resistance to venetoclax can develop, limiting its long-term efficacy.
  • Mcl-1, a related protein, often plays a role in this resistance as it is not targeted by venetoclax.

Purpose of the Study:

  • To explore combination strategies to overcome venetoclax resistance.
  • To investigate the role of Mcl-1 in venetoclax resistance.
  • To identify new therapeutic approaches for hematologic malignancies.

Main Methods:

  • Review of existing literature on venetoclax and resistance mechanisms.
  • Analysis of rational combination strategies targeting compensatory survival pathways.
  • Focus on Mcl-1 downregulation as a key resistance-circumventing approach.

Main Results:

  • Venetoclax is a promising agent for various blood cancers.
  • Resistance to venetoclax is a significant clinical challenge.
  • Combination therapies, particularly those involving Mcl-1 inhibition, are being developed to address resistance.

Conclusions:

  • Combination strategies are crucial for overcoming venetoclax resistance.
  • Targeting Mcl-1 is a promising approach to enhance venetoclax efficacy.
  • These combination strategies are expected to become part of future cancer treatment regimens.
Keywords:
Venetoclaxcombination strategiesresistance

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