Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Markers for bone sarcomas

Introduction The classification of bone sarcomas is still today mainly based on the comparison of histological, clinical, and radiological criteria. This classification evolves with the improvement of knowledge on the mechanisms of carcinogenesis of these tumors which results in the detection of biomarkers detectable by immunohistochemical, genetic, or biochemical techniques. This development is responsible for the description of new entities and the reclassification of certain tumors.…

Genetic aspects of primary bone tumors

Research highlights Recurrent genomic rearrangements and specific somatic mutations in bone tumors are leading to new diagnostic tests. Deregulated fusion transcription factors are revealing how epigenomic changes may underlie Ewing's sarcoma oncogenesis. Deep sequencing studies have contributed toward improved understanding of the complex genomics of osteosarcoma. Specific genetic alterations are identifying driver pathways in bone tumors that are new therapeutic opportunities. Introduction Primary neoplasms of the…

Cytogenetics of bone tumors

Introduction After the discovery of the Philadelphia chromosome in patients with chronic myeloid leukemia [ ], investigators in the cancer field tried to find other associations between chromosomes and cancer, including bone tumors [ ]. The cytogenetic findings of bone tumors have shown findings of very extreme heterogeneity including loss or gain of chromosomes, deletion or duplication of chromosomal segments, and double minutes or homogeneously stained…

Disseminated tumor cells in bone marrow of cancer patients : biology and clinical relevance

Acknowledgments K.P. is supported by European Research Council Advanced Investigator Grant “INJURMET”; C.A-P. is supported by the National Institute of Cancer (INCa, ) and SIRIC Montpellier Cancer Grant INCa_Inserm_DGOS_12553; K.P. and C.A-P. are both supported by the ERA-NET TRANSCAN 2 JTC 2016 PROLIPSY and the ELBA project that has received funding from the European Union Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie…

Liquid biopsy in bone sarcomas and identification of new biomarkers

Bone sarcoma malignancies: origin, treatment, and diagnosis Bone sarcomas are rare, highly heterogeneous oncologic entities that originate in mesenchymal tissues from bone. Primary bone cancers account for less than 0.2% of all cancers. The high morphological heterogeneity of cancer cells and tumor tissues leads to multiple biological behaviors that require specific and complex therapeutic strategies. Osteosarcoma, Ewing sarcoma (ES), and chondrosarcoma are the most prevalent bone…

Long noncoding RNA and bone sarcoma

Research highlights lncRNAs promote tumorigenesis, chemotherapeutic resistance, and metastasis in bone sarcomas. Notable examples include MALAT1, TUG1, XIST, NEAT1, SNHG12, and UCA1. lncRNAs have emerged as promising diagnostic and prognostic biomarkers, as well as veritable therapeutic targets in bone sarcomas. Introduction Epigenetics encompasses the molecular changes that affect gene expression without direct alteration of the primary DNA sequence. Examples include DNA methylation, chromatin modification, nucleosome positioning,…

MicroRNAs and bone metastasis: how small RNAs regulate secondary tumor formation and progression in the skeleton

Introduction Cancer metastasis occurs when cancer cells from a primary tumor spread to distant organs, with bone being one of the most common sites for breast, prostate, and lung cancers [ ]. Patients with secondary bone tumors usually show osteolytic lesions (bone destruction) when cancer cells derive from breast and lung cancers, while they show osteoblastic lesion (abnormal bone formation) when cells derive from prostate cancer.…

MicroRNA implication in therapeutic resistance and metastatic dissemination of bone-associated tumors

Introduction Breast cancer and prostate cancer are the most frequently diagnosed cancers of women and men, respectively, living in developed countries with more than 1 million new cases per year worldwide. Despite the progresses made in the development of new treatments, mortality of cancer patients is still highly linked to the occurrence of distant metastasis. More than 70% of breast and prostate cancer patients present bone…

Epigenetic heterogeneity in primary bone cancers

Research highlights The epigenome defines cellular identity and is frequently dysregulated in primary bone cancers Aberrant epigenetic modifications in these cancers are promising drug targets Epigenetic heterogeneity is a characteristic of primary bone cancers Novel technologies for analyzing epigenetic heterogeneity will empower precision medicine Introduction The term epigenetics refers to the study of mechanisms of gene regulation that are not directly encoded in the DNA sequence…

Bone remodeling markers and bone cancer

Abbreviations BAP Serum bone alkaline phosphatase BMD Bone mineral density BSP Bone sialoprotein CTX-I Epitope of C-terminal cross-linked telopeptide of collagen type I DPD Deoxypyridinoline ICTP Epitope of C-terminal cross-linked telopeptide of collagen type I LSC Least significant change MGUS Monoclonal gammopathy of undetermined significance NSCLC Non–small cell lung cancer NTX-I N-terminal cross-linked telopeptide of collagen type I OC Osteocalcin PICP C-terminal propeptide of procollagen type…

Dormancy in cancer bone metastasis

Introduction Several cancers are well characterized for their predilection to invade bone, from which breast cancer (BCa), prostate cancer (PCa), and lung cancer (LCa) are on top of the list. It is estimated that ~70% of the patients with PCa and BCa will develop bone metastasis and ~40% of patients with LCa will do so too [ ]. The development of bone metastasis significantly increases the…

EMT process in bone metastasis

Introduction Epithelial—mesenchymal transition (EMT) was originally described as a fundamental process essential for developmental programs including formation of mesoderm, neural crest, heart valve, palatogenesis, and myogenesis [ ]. During the EMT process, the epithelial cells transition from polarized, cobblestone-like cells to migratory, spindle-shaped mesenchymal cells. In addition to morphological changes, cells undergoing EMT also exhibit changes at the molecular level by losing expression of epithelial markers…

Energy metabolism in bone tumors: fuel selection and adaptation

Research highlights High diversity of metabolic fuels to feed bone tumor. Strong energetic metabolism genes program allow tumor cells to survive and progress in bone microenvironment. Osteomimicry may contribute to bone tumor adaptation to their metabolic environment. Introduction Bone tumors include primary bone tumor like osteosarcoma (OS) and bone metastases, which are frequent complications of many cancers but are especially common from breast and prostate cancer.…

Hypoxia-inducible factor (HIF)–mediated effects of the hypoxic niche in bone cancer

Research highlights Hypoxia in the primary tumor, as well as low levels of oxygen in the bone marrow, increases the risk of bone invasion. HIF-induced genes in primary tumors (e.g., LOX, PKM2) specifically direct metastasis to bone sites. Hypoxia downregulates dormancy genes (e.g., LIFR), driving exit from dormancy and induction of osteolytic lesions. HIF contributes to an unfavorable immune profile in Ewing's sarcoma, which promotes poor…

Impact of the acid microenvironment on bone cancers

Introduction Intratumor extracellular proton accumulation is a well-established hallmark of malignancy in solid tumors [ ]. Similarly to hypoxia [ ], acidosis influences the behavior of cancer cells and the clinical outcome by modulating tumor stemness, invasion, invadopodia formation, metastasis, anticancer immune response, and response to therapy [ , ]. Bone cancers [ ] are characterized by an extracellular pH (pHe) ranging 6.4 to 7.3, whereas…

Role of classical cannabinoid receptors in cancer-associated bone disease

Abbreviations 2-AG 2-Arachidonoylglycerol ACEA Arachidonyl-2-chloroethylamide CB1 Cannabinoid receptor type 1 CB2 CB type 2 CB Cannabinoid CBD Cannabidiol Endocannabinoid Endogenous cannabinoid FAAH Fatty acid amide hydrolase GFP Green fluorescent protein IC50 Half-maximal inhibitory concentration MAGL Monoacylglycerol lipase Micro-CT Micro–computed tomography MM Multiple myeloma THC Delta(9)-Tetrahydrocannabinol Acknowledgments The author would like to thank laboratory technicians, students, researchers, and leaders who dedicated their time and resources for testing…

Connexin43 and development of primary bone tumors: osteosarcoma and Ewing’s sarcoma

Gap junction channels According to Schleiden's theory, cells are autonomous units that are circumscribed by a diffusion barrier that is able to prevent any exchange with the surrounding cells [ ]. However, in the late 1960s, Kanno and Loewenstein demonstrated that the fluorescein, a molecule of 376 Da, can pass freely from one cell to another [ ]. In this context, Loewenstein and coll. have proposed…

Extracellular vesicles, tumor growth, and the metastatic process

Highlights The effects of tumor-derived EVs appear to be variable and dependent upon their cargos. EVs, via their cargos, can mediate the transfer of malignant traits between cancer cells. EV therapies have progressed to phase I and phase II clinical trials for melanoma, lung, and non–small cell carcinoma. Understanding how EV heterogeneity affects cancer progression remains a key challenge. Introduction Extracellular vesicles (EVs) has become the…

Transforming growth factor-β and its signaling pathway in skeletal complications of malignancy

Research highlights TGF-β is abundant in bone and a critical coupling factor in bone cells during bone remodeling. Cancer frequently affects bone as primary bone cancer or during bone metastases. TGF-β signaling in cancer has dual roles, as a tumor suppressor or a tumor and metastasis promoter. TGF-β in cancer cells or in the microenvironment contributes to the progression of the disease. Anti-TGF-β therapies, while efficient…