Abstract：
:Amino-bisphosphonates (N-BPs) have been commercially available for over four decades and are used for the treatment of osteoporosis, Paget's disease, hypercalcemia of malignancy, and bone metastases derived from various cancer types. Zoledronate and alendronate, two of the most potent N-BPs, have demonstrated direct tumoricidal activity on tumor cells and immune modulatory effects on myeloid cells and T cells in vitro and in animal models of cancer. However, the rapid renal clearance and sequestration in mineral bone of these drugs in free form severely limit their systemic exposure and applications in cancer patients. Reformulation of N-BPs by encapsulation in liposomal nanoparticles addresses these pharmacokinetic barriers, and liposomal zoledronate and alendronate formulations have been found to increase the anticancer efficacy of cytotoxic chemotherapies and adoptive T cell immunotherapies in murine cancer models. Herein, we review the differences in pharmacology between N-BPs versus non-N-BPs (e.g., clodronate), free versus liposomal N-BP formulations, and targeted versus non-targeted liposomal N-BPs, and the clinical and preclinical evidence supporting a role for liposomal N-BPs in the treatment of cancer. We propose that pegylated liposomal alendronate (PLA) has the most potential for clinical translation based on favorable therapeutic index, ability to passively target and accumulate in tumors, proven biocompatibility of the liposome carrier, and preclinical anticancer efficacy.
journal_name
Semin Cancer Bioljournal_title
Seminars in cancer biologyauthors
La-Beck NM,Liu X,Shmeeda H,Shudde C,Gabizon AAdoi
10.1016/j.semcancer.2019.12.001subject
Has Abstractpub_date
2019-12-23 00:00:00eissn
1044-579Xissn
1096-3650pii
S1044-579X(19)30396-7pub_type
杂志文章,评审abstract：:Glioblastoma (GBM) is an aggressive and incurable brain tumor; its malignancy has been associated with the activity of tumor infiltrating myeloid cells. Myeloid cells play important roles in the tumor control by the immune response, but also in tumor progression. Indeed, GBM exploits multiple mechanisms to recruit and...
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abstract：:Gynaecological carcinosarcomas are the most lethal gynaecological malignancies that are often highly resistant to standard chemotherapy. They are composed of both carcinomatous and sarcomatous components and are associated with high rates of metastatic disease. Due to their rarity, molecular studies have been carried ...
journal_title：Seminars in cancer biology
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journal_title：Seminars in cancer biology
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abstract：:The ski oncogene is the transforming gene, v-ski, of the defective SKV avian carcinoma viruses. V-ski transformation causes increased proliferation of embryo fibroblasts and also induces a number of genes characteristic of the muscle lineage. In natural SKV isolates the 49 kDa v-ski polypeptide is expressed as a fusio...
journal_title：Seminars in cancer biology
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journal_title：Seminars in cancer biology
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journal_title：Seminars in cancer biology
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journal_title：Seminars in cancer biology
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1996.0009
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journal_title：Seminars in cancer biology
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
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pub_type： 杂志文章,评审
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abstract：:The tumor microenvironment (TME) is a complex meshwork of extracellular matrix (ECM) macromolecules filled with a collection of cells including cancer-associated fibroblasts (CAFs), blood vessel associated smooth muscle cells, pericytes, endothelial cells, mesenchymal stem cells and a variety of immune cells. In tumor...
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abstract：:The key molecule for normal B cells is the surface Ig (sIg) of the B-cell receptor, which influences cell behaviour, even after neoplastic transformation. During B-cell maturation, sIg accumulates somatic mutations in the Ig variable region (V) genes and tumours retain these patterns, thereby revealing the point of di...
journal_title：Seminars in cancer biology
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abstract：:More than 70% of gastrointestinal (GI) cancers are diagnosed with metastases, leading to poor prognosis. For some cancer patients with limited sites of metastatic tumors, the term oligometastatic disease (OMD) has been coined as opposed to systemic polymetastasis (PMD) disease. Stephan Paget first described an organ-s...
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abstract：:We have found that not all Epstein-Barr viral (EBV) plasmids are duplicated each cell cycle. This inefficiency is intrinsic to EBV's mechanism of DNA synthesis in latently infected cells and necessarily leads to a loss of EBV plasmids from proliferating cells. If EBV provides its host cells advantages that allow those...
journal_title：Seminars in cancer biology
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abstract：:Mitochondria-shaping proteins control the dynamic equilibrium between fusion and fission of the mitochondrial network. Their balance is strictly required to regulate various processes, including the quality of mitochondria, cell metabolism, cell death, proliferation and cell migration. Alterations in these processes a...
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abstract：:P-element-induced wimpy testis (PIWI) interacting RNAs (piRNAs) are a class of small regulatory RNAs mechanistically similar to but much less studied than microRNAs and small interfering RNAs. Today the best understood function of piRNAs is transposon control in animal germ cells, which has earned them the name 'guard...
journal_title：Seminars in cancer biology
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abstract：:While current treatment regimens for acute leukemia can dramatically improve patient survival, there remains room for improvement. Due to its roles in cell differentiation, cell survival, and apoptotic signaling, modulation of the cyclic AMP (cAMP) pathway has provided a meaningful target in hematological malignancies...
journal_title：Seminars in cancer biology
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abstract：:The B-cell receptor (BCR) is essential for normal B-cell development and maturation. In an increasing number of B-cell malignancies, BCR signaling is implicated as a pivotal pathway in tumorigenesis. Mechanisms of BCR activation are quite diverse and range from chronic antigenic drive by microbial or viral antigens to...
journal_title：Seminars in cancer biology
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