Novel and Conventional Preclinical Models to Investigate Bone Metastasis

Abstract

Purpose of Review The purpose of this review is to emphasize the use of bone metastasis models in preclinical research. As classical models have been thoroughly discussed in recent reviews, we here highlight the most important aspects from these papers with a special focus on novel models developed during the past 5 years. Recent Findings Preclinical mouse models to study bone metastasis can be divided by cancer cell inoculation techniques (spontaneous, systemic, or local) or by immunological background of the mice (immunodeficient, syngeneic, or humanized). Additionally, novel computational, in vitro co-culture, and humanized bone models have been established. Summary Various models can be used to approach distinct research questions. Understanding limitations of the models is essential when planning a study and interpreting the results. Development of novel models will increase understanding of the complex biology and advance the discovery of new therapies targeting bone metastases.

Insights into immuno-oncology drug development landscape with focus on bone metastasis

“…Some other drugs had data showing effects for inhibiting or decreasing growth of lymph node or lung metastases, but these metastases are very different from bone metastases and results obtained on other metastases are usually not translatable to bone metastases. One reason for the lack of preclinical studies in bone metastasis models could be the special expertise needed to carry out studies in these technically challenging models ( 78 ). We have recently published results on how effects of immunotherapies can be addressed in proper metastasis models ( 79 , 80 ) and we hope that metastasis models would be extensively used at preclinical development stages to confirm the efficacy before initiating clinical studies.…”

Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy

“…With respect to the systemic models, the seeds (cancer cells) are injected systematically, and then accumulate in the preferred soil (bones). The systemic models are considered very close to real bone metastases given that they simulate the early stages from survival in circulation, extravasation, and dissemination to the bone to eventual dormancy and/or growth of bone metastases 369 . Unfortunately, tumors may arise in several sites more than the bones after the systematic injection of cancer cells which may perplex the evaluation of skeletal complications 370 , 371 .…”

“…However, it should be noted that these inoculation models obviously cannot model the process starting from the primary tumors or pre-metastatic niches. To date, scarce models are found to outline the whole metastatic range from the primary tumor to final metastases and skeletal complications, in which the 4T1 syngeneic model of breast cancer represents one such model 369 , 370 , 372 . Due to the intrinsic connection with bone cancer pain, these models are also utilized to address cancer pain, another common complication along with late-stage cancers 373 .…”

Spontaneous and Induced Animal Models for Cancer Research

“…However, such enhanced metastatic pattern is lethal for many organs, and for this reason, the intra-caudal induction pathway is preferred. In addition, this recently discovered route can facilitate our understanding of such a complex process as bone metastasis [145].…”