Bone Metastases and Health in Prostate Cancer: From Pathophysiology to Clinical Implications

Abstract

Clinically relevant bone metastases are a major cause of morbidity and mortality for prostate cancer patients. Distinct phenotypes are described: osteoblastic, the more common osteolytic and mixed. A molecular classification has been also proposed. Bone metastases start with the tropism of cancer cells to the bone through different multi-step tumor–host interactions, as described by the “metastatic cascade” model. Understanding these mechanisms, although far from being fully elucidated, could offer several potential targets for prevention and therapy. Moreover, the prognosis of patients is markedly influenced by skeletal-related events. They can be correlated not only with bone metastases, but also with “bad” bone health. There is a close correlation between osteoporosis—a skeletal disorder with decreased bone mass and qualitative alterations—and prostate cancer, in particular when treated with androgen deprivation therapy, a milestone in its treatment. Systemic treatments for prostate cancer, especially with the newest options, have improved the survival and quality of life of patients with respect to skeletal-related events; however, all patients should be evaluated for “bone health” and osteoporotic risk, both in the presence and in the absence of bone metastases. Treatment with bone-targeted therapies should be evaluated even in the absence of bone metastases, as described in special guidelines and according to a multidisciplinary evaluation.

Bioinformatics analysis reveals link between alternative complement cascade pathway and colorectal cancer liver metastasis

“…Another gene network frequently modi ed in liver metastasis of colorectal cancer is the TGFβ signaling pathway, which regulates cell growth and the development and differentiation of multiple tumor types [38] . MiR-378g can directly target PMEPA1, a TGF-β signaling regulator, inhibiting prostate cancer bone metastasis [39] . Furthermore, the KEGG pathway analysis revealed the involvement of the complement pathway in CRC metastasis for the rst time.…”

“…As a major part of innate immunity, many complement components play key regulatory roles in the tumor microenvironment during cancer progression. For example, complement anaphylactotoxins directly or indirectly inhibit anti-tumor t cell responses at primary and metastatic sites, promote tumor cell proliferation, accelerate tumor metastasis and angiogenesis, and reduce the immune system response to tumors [11] . Complement system activation within the tumor liberates complement components, such as C1q, C3a, and C5a, into the tumor microenvironment (TME), fostering tumorigenesis.…”

Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer

“…The first step of metastasis requires the escape of metastasizing tumor cells from the primary tumor into circulation. This invasion and intravasation are driven by tumor cell-intrinsic mechanisms, their associated stroma, and the local extracellular matrix (ECM) surrounding the primary tumor [13][14][15]. The suitable pre-metastatic niche must evolve to allow tumor cell engraftment (metastatic niche) and proliferation (micro-and macrometastatic transition).…”

Akuter Querschnitt unter Systemtherapie – Radiotherapie oder OP?

“…Tumorbiologisch neigt das Prostatakarzinom zur Ausbildung von Läsionen in den Wirbelkörpern, die in der Regel osteoblastischer Natur sind, es können aber auch osteolytische Metastasen auftreten [7]. Neben dem Leitsymptom des Rückenschmerzes können sich radikuläre Schmerzmuster mit neurologischen Ausfallerscheinungen bis hin zum Vollbild eines Querschnittsyndroms präsentiereneinem gefürchteten tumororthopädischen bzw.…”