Table 1 Overview of processes determining the anti-tumour effects of bisphosphonates outside bone
From: Anti-tumour activity of bisphosphonates in preclinical models of breast cancer
Factors contributing to anti-tumour effects of BPs in peripheral tumours | Questions still to be resolved |
|---|---|
Concentration in tumour | What concentration of BPs reaches the tumour following a clinical dose? |
Cellular uptake | How much BP is taken up by the tumour cells and by the cells of the local tumour microenvironment? |
Duration and clearance | How long is BP retained in the cells and within the tumour mass? |
Molecular and cellular targets | What are the specific molecular targets of BPs in tumour cells and in the cells of the tumour microenvironment? |
Systemic effects | BPs may reduce the levels of circulating factors like VEGF, thereby affecting tumour growth indirectly |
Effects on bone marrow precursors | BPs may inhibit recruitment of bone marrow precursors essential for primary tumour growth |
Activation of γδ T cells | BPs may facilitate tumour killing through activation of anti-tumourigenic γδ T cells |
Release of BPs from bone | Does long-term release of low levels of BPs during normal bone turnover reach levels that affect peripheral tumours? |