Title:Relevance of Micrometastases and Targeting the Bone Marrow Niche with Zoledronic Acid in Breast Cancer
Volume: 8
Issue: 2
Author(s): Rebecca Aft
Affiliation:
Keywords:
Cancer, circulating tumor cells, disseminated tumor cells, metastatic niche, zoledronic acid
Abstract: During the course of cancer metastasis development, invasive tumor cells circulate through the blood stream
and disseminate to other tissues. Circulating and disseminated tumor cells (CTCs and DTCs, respectively) may be the
source of local and distant metastases and are a promising target for anticancer therapy. Multiple studies have shown that
the detection of DTCs or CTCs correlates with increased risk of disease recurrence, suggesting that reducing the prevalence
and persistence of these cells is clinically relevant. The development of metastases is a multistep process that involves
complex biologic processes and a multitude of growth factors. The bone marrow provides a portion of these
growth factors and a nutrient-rich microenvironment in which dormant cancer cells can survive and transition to metastasis-
initiating cells. The molecular interactions between DTCs and the bone marrow microenvironment enable DTCs to
evade cytotoxic chemotherapy, allowing them to lie dormant for extended periods of time before becoming active and metastasizing
to secondary sites. Alteration of the bone marrow microenvironment with antiresorptive agents, such as
bisphosphonates, may render the bone marrow less suitable for cancer cell growth, possibly interfering with the metastatic
cascade. Clinical studies have shown that the nitrogen-containing bisphosphonate zoledronic acid can reduce the persistence
and prevalence of DTCs in patients with breast cancer, suggesting that zoledronic acid may improve clinical outcomes.
Targeting the metastatic niche by altering the microenvironment in the bone marrow may be an effective anticancer
strategy.
