Lobular breast cancer: molecular basis, mouse and cellular models

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Infiltrating lobular breast cancer (ILC) is the most common special breast cancer subtype.
• ILC is uniquely characterized by the mutational or epigenetic inactivation of E-cadherin (CDH1).
• Loss of E-cadherin function is central to ILC development, supported by genetic evidence in humans and animal models.

Purpose of the Study:

• To provide a comprehensive overview of available models for studying ILC.
• To evaluate the advantages and limitations of different ILC models.
• To discuss the molecular mechanisms of E-cadherin loss in ILC development and therapeutic resistance.

Main Methods:

• Review of existing literature on ILC models.
• Analysis of cell lines, xenograft tumors, and genetically engineered mouse models.
• Evaluation of model representativeness for human ILC.

Main Results:

• Detailed assessment of various ILC models, highlighting their strengths and weaknesses.
• Discussion of incompletely defined mechanisms linking E-cadherin loss to malignant transformation.
• Identification of candidate genes and pathways involved in ILC progression and resistance.

Conclusions:

• Physiologically relevant and functional ILC models are crucial for advancing beyond descriptive studies.
• Current models offer insights into E-cadherin's role in ILC pathogenesis.
• Further research using these models can elucidate ILC development, progression, and resistance mechanisms.