Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer

Pieter A Roelofs1,2, John W M Martens3, Reuben S Harris2,4,5

  • 1Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.

Insights

APOBEC3 enzymes drive cancer mutations and resistance, particularly in breast cancer. Detecting APOBEC3 activity could offer new biomarkers and therapeutic targets for improved cancer treatment.

Area of Science:

  • Biochemistry and Molecular Biology
  • Genetics and Genomics
  • Oncology

Background:

  • The APOBEC3 (apolipoprotein B mRNA editing catalytic polypeptide-like 3) family of cytosine deaminases is increasingly recognized for its role in cancer genome mutagenesis.
  • This mutagenesis contributes to genomic heterogeneity within and between tumors, impacting therapeutic resistance in various cancers, including breast cancer.

Approach:

  • This review comprehensively examines recent advancements in detecting APOBEC3-mediated mutagenesis.
  • It summarizes the regulatory pathways controlling APOBEC3 enzyme expression.
  • The clinical impact and potential therapeutic opportunities presented by APOBEC3 enzymes are explored.

Key Points:

  • APOBEC3 enzymes are significant drivers of cancer genome mutations.
  • Dysregulated APOBEC3 expression is linked to intratumor heterogeneity and therapy resistance.
  • Understanding APOBEC3 detection methods and expression is crucial for clinical applications.

Conclusions:

  • APOBEC3-mediated mutagenesis shows promise as a predictive biomarker in breast cancer treatment.
  • APOBEC3 enzymes represent a potential novel therapeutic target for cancer therapy.

Related Concept Videos

Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.1K
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.1K
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...
6.7K
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...
7.8K