Metastatic Breast Cancer: Review of Emerging Nanotherapeutics

Abstract

Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed by combining current cancer therapies with nanotechnology. The applications of nanotherapeutics for both primary and metastatic BC treatments are developing rapidly, and new ideas and technologies are being discovered. Several recent reviews covered the advancement of nanotherapeutics for primary BC, while also discussing certain aspects of treatments for metastatic BC. This review provides comprehensive details on the recent advancement and future prospects of nanotherapeutics designed for metastatic BC treatment, in the context of the pathological state of the disease. Furthermore, possible combinations of current treatment with nanotechnology are discussed, and their potential for future transitions in clinical settings is explored.

Keywords: breast cancer; metastasis; nanotherapeutics.

Figure 1

The vicious cycle between BC cells and bone. Tumor cells interact with both osteoclasts and osteoblasts in the bone microenvironment, leading to a local increase in tumor-derived factors that promote osteoclastogenesis and osteoblastogenesis. Mature osteoclasts subsequently release survival factors that include insulin-like growth factor 1 (IGF-1) and transforming growth factor beta (TGF-β), which promote the proliferation and survival of tumor cells [51].

Figure 2

Schematic depicting the generation of ALN-NPs, as well as the process of combined bone-targeting and pH-responsive release of bortezomib resulting from the aryl boronate linkage as an antimetastatic therapy. ALN: alendronate; Cat: catechol; BTZ: bortezomib [54].

Figure 3

Bone-targeted nanoplatform combining zoledronate and photothermal therapy in order to treat breast cancer bone metastasis. The system contains gold nanorods enclosed inside zoledronic acid-functionalized mesoporous silica nanoparticles (Au@MSNs) [53]. (Reprinted/adapted with permission from Ref. [53]. 2023, Marya Ahmed).

Figure 4

Mechanisms associated with the formation of hematogenous metastasis to the brain [80,81].

Figure 5

Different strategies utilized for the active and passive targeting against brain metastases of BC to overcome the hurdles associated with the BBB.

Figure 6

Schematic displaying the mechanistic steps associated with lung metastasis of BC.