The role of biomarkers in the management of bone-homing malignancies

Bone represents a common site of metastasis from several solid tumours, including breast, prostate and lung malignancies. The onset of bone metastases (BM) is associated not only with serious skeletal complications, but also shortened overall survival, owing to the lack of curative treatment options for late-stage cancer. Despite the diagnostic advances, BM detection often occurs in the symptomatic stage, underlining the need for novel strategies aimed at the early identification of high-risk patients. To this purpose, both bone turnover and tumour-derived markers are being investigated for their potential diagnostic, prognostic and predictive roles. In this review, we summarize the pathogenesis of BM in breast, prostate and lung tumours, while exploring the current research focused on the identification and clinical validation of BM biomarkers

Cancer Treatment and Bone Health

Considerable advances in oncology over recent decades have led to improved survival, while raising concerns about long-term consequences of anticancer treatments. In patients with breast or prostate malignancies, bone health is a major issue due to the high risk of bone metastases and the frequent prolonged use of hormone therapies that alter physiological bone turnover, leading to increased fracture risk. Thus, the onset of cancer treatment-induced bone loss (CTIBL) should be considered by clinicians and recent guidelines should be routinely applied to these patients. In particular, baseline and periodic follow-up evaluations of bone health parameters enable the identification of patients at high risk of osteoporosis and fractures, which can be prevented by the use of bone-targeting agents (BTAs), calcium and vitamin D supplementation and modifications of lifestyle. This review will focus upon the pathophysiology of breast and prostate cancer treatment-induced bone loss and the most recent evidence about effective preventive and therapeutic strategies

ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors

Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases

Le strutture di combustione: è tutta una questione di relazioni?

The hearth structure is one of the most frequent artefact of an archaeological deposit and it can be defined as “an evidence connected to the fire use”. The identification of these structures in the archaeological deposit can therefore be simple, if this appears as a discreditable installation (a hearth, an oven etc.), but in some cases the understanding of their function can be problematic. The same structure can have uses or it can perform different functions at the same time, so considering their multi-functional nature, often it is possible to reduce the range of functions evaluating the presence of some "accessories" and investigating the relationships with other elements of the context, through a systemic approach. Far from providing coherent and non-contradictory information, some considerations will be presented on the basis of some experimental research conducted, focused on hearths and cooking platforms: i) fuels used in prehistoric communities; ii) thermal alterations of the supports; iii) the formation of deposits; These results could contribute to the structures classification and provide ideas about methods and tools to analyse some contexts of Southern Italy characterized by the structures connected with the use of fire.La struttura di combustione è un manufatto fra i più frequenti di un deposito archeologico e può definirsi “come un’evidenza antropica connessa con l'uso del fuoco”. L’identificazione delle strutture di combustione può essere un’operazione piuttosto semplice, se questa appare come un’istallazione discretizzabile (un focolare, un forno, etc.), ma in alcuni casi la comprensione della loro funzione può risultare problematica. Data la loro natura polifunzionale, è possibile ridurre il range delle funzioni possibili, o comprenderne l’ultima fase di utilizzo, valutando la presenza di alcuni “accessori” e indagando le relazioni con altri elementi del contesto attraverso un approccio sistemico. Lungi dal fornire informazioni coerenti e non contraddittorie saranno esposte alcune considerazioni frutto di ricerche sperimentali, condotte su focolari e piastre di cottura focalizzate su: ì) combustibili utilizzati nelle comunità preistoriche, ii) alterazioni termiche dei supporti, iii) formazione dei depositi. Tali considerazioni potrebbero dare un contributo alla classificazione delle strutture, suggerire metodi e strumenti di indagine dei contesti connessi con l’uso del fuoco. Saranno esposti i risultati delle ricerche condotte in contesti dell’età del Bronzo dell’Italia meridionale, caratterizzati dalla presenza di strutture di combustione semplici che documentano alcune delle attività quotidiane connesse con l’uso del fuoco