3D Tumor Models for Breast Cancer: Whither We Are and What We Need

Three-dimensional
(3D) models have led to a paradigm shift in disease
modeling in vitro, particularly for cancer. The past
decade has seen a phenomenal increase in the development of 3D models
for various types of cancers with a focus on studying stemness, invasive
behavior, angiogenesis, and chemoresistance of cancer cells, as well
as contributions of its stroma, which has expanded our understanding
of these processes. Cancer biology is moving into exploring the emerging
hallmarks of cancer, such as inflammation, immune evasion, and reprogramming
of energy metabolism. Studies into these emerging concepts have provided
novel targets and treatment options such as antitumor immunotherapy.
However, 3D models that can investigate the emerging hallmarks are
few and underexplored. As commonly used immunocompromised mice and
syngenic mice cannot accurately mimic human immunology, stromal interactions,
and metabolism and require the use of prohibitively expensive humanized
mice, there is tremendous scope to develop authentic 3D tumor models
in these areas. Taking the specific case of breast cancer, we discuss
the currently available 3D models, their applications to mimic signaling
in cancer, tumor–stroma interactions, drug responses, and assessment
of drug delivery systems and therapies. We discuss the lacunae in
the development of 3D tumor models for the emerging hallmarks of cancer,
for lesser-explored forms of breast cancer, and provide insights to
develop such models. We discuss how the next generation of 3D models
can provide a better mimic of human cancer modeling compared to xenograft
models and the scope toward preclinical models and precision medicine.