New-Generation Hormone Therapies in Nonmetastatic Castration-Resistant Prostate Cancer: Why, Who, When

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The combination of bevacizumab with chemotherapy is more beneficial in the metastatic setting rather than in the adjuvant setting for the treatment of HER2-negative breast cancer—a commentary on the E5103 randomized phase III clinical study

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Optimal primary end point in Phase II trials of immune checkpoint inhibitors for advanced solid cancers: An evolving issue

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The fibroblast growth factor receptors in breast cancer: From oncogenesis to better treatments

Breast cancer (BC) is the most frequent form of malignancy and second only to lung cancer as cause of deaths in women. Notwithstanding many progresses made in the field, metastatic BC has a very poor prognosis. As therapies are becoming more personalized to meet the needs of patients, a better knowledge of the molecular biology leading to the disease unfolds the possibility to project more precise compounds or antibodies targeting definite alteration at the molecular level and functioning on such cancer-causing molecules expressed in cancer cells of patients, or present as antigens on the surface of cancer cell membranes. Fibroblast growth factor receptor (FGFR) is one of such druggable targets, activated by its own ligands -namely the Fibroblast Growth Factors (FGFs). This pathway provides a vast range of interesting molecular targets pursued at different levels of clinical investigation. Herein we provide an update on the knowledge of genetic alterations of the receptors in breast cancer, their role in tumorigenesis and the most recent drugs against this particular receptor for the treatment of the disease

Rééducation Posturale Globale in musculoskeletal diseases: scientific evidence and clinical practice

SUMMARY Several studies on the treatment of musculoskeletal diseases with physiotherapy and clinical experiences on the basis of a method called Rééducation Posturale Globale (RPG), have highlighted the usefulness of this treatment. Although such treatment technique is commonly used in physical therapy practice, only few studies support its therapeutic effectiveness. Objective: To search the literature for evidence of RPG effectiveness, in order to identify the most appropriate therapeutic contexts for its use. Methods: A review of the literature through the following databases: PubMed, Embase, Cinahl, Pedro, and Medscape. The keywords used for the search in the databases are: Rééducation Posturale Globale, Souchard, Posture, and Manual Therapy. The following clinical studies were selected: randomized controlled studies, non-randomized controlled studies, observation studies, and case reports, in English, Spanish, Portuguese, and Italian. Results: Out of 18 studies found, 9 were analyzed: 2 randomized controlled studies, 2 non-randomized controlled studies, 3 non-controlled studies, and 2 case reports. Conclusions: The RPG method has been shown to be an effective treatment technique for musculoskeletal diseases, in particular for ankylosing spondylitis, acute and chronic low back pain, and lumbar discherniation. Although the scarcity of rigorous experimental trials on a large scale does not allow the drawing of undisputable conclusions, the results gathered up to now are an encouragement to carry on research in the field of conservative treatment

Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function.

The Notch signaling pathway and the delta-like 4 ligand (DLL4) play key roles in embryonic vascular development. Many of the pathways involved in embryonic vascular development also play important roles in tumor angiogenesis. In this study, we assessed the expression of DLL4 in primary renal cancer and investigated the biological function of DLL4 in primary endothelial cells. Using real-time quantitative PCR and in situ hybridization, we showed that the expression of DLL4 was up-regulated within the vasculature of clear cell-renal cell carcinoma almost 9-fold more than normal kidney and was correlated with the expression of vascular endothelial growth factor (VEGF). The expression of DLL4 in endothelial cells was up-regulated by VEGF and basic fibroblast growth factor synergistically, and by hypoxia through hypoxia-inducible factor 1alpha. Down-regulation of DLL4 expression with RNA interference led to decreased expression of HEY1 and EphrinB2, and the inhibition of endothelial cell proliferation, migration, and network formation, all of which are important processes in tumor angiogenesis. The inhibition of proliferation occurred via the induction of cell cycle arrest in G0-G1 by increased expression of p21 and decreased phosphorylation of retinoblastoma. We conclude that an optimal window of the DLL4 expression is essential for tumor angiogenesis and that selective modulation of the DLL4 expression within human tumors may represent a potential novel antiangiogenic therapy

Endocrine‐based treatments in clinically‐relevant subgroups of hormone receptor‐positive/her2‐negative metastatic breast cancer: Systematic review and meta‐analysis

A precise assessment of the efficacy of first-/second-line endocrine therapies (ET) +/- target therapies (TT) in clinically-relevant subgroups of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) has not yet been conducted. To improve our current knowledge and support clinical decision-making, we thus conducted a systematic literature search to identify all first-/second-line phase II/III randomized clinical trials (RCT) of currently approved or most promising ET +/- TT. Then, we performed a meta-analysis to assess progression-free (PFS) and/or overall survival (OS) benefit in several clinically-relevant prespecified subgroups. Thirty-five RCT were included (17,595 patients). Pooled results show significant reductions in the risk of relapse or death of 26-41% and 12-27%, respectively, depending on the clinical subgroup. Combination strategies proved to be more effective than single-agent ET (PFS hazard ratio (HR) range for combinations: 0.60-0.65 vs. HR range for single agent ET: 0.59-1.37; OS HR range for combinations: 0.74-0.87 vs. HR range for single agent ET: 0.68-0.98), with CDK4/6-inhibitors(i) + ET being the most effective regimen. Single agent ET showed comparable efficacy with ET+TT combinations in non-visceral (p = 0.63) and endocrine sensitive disease (p = 0.79), while mTORi-based combinations proved to be a valid therapeutic option in endocrine-resistant tumors, as well as PI3Ki + ET in PIK3CA-mutant tumors. These results strengthen international treatment guidelines and can aid therapeutic decision-making

Nanoparticle albumin-bound paclitaxel: a big nano for the treatment of gastric cancer

Gastric cancer (GC) is the third cause of cancer-related death worldwide. Patients with unresectable GC can be treated with chemotherapy such as paclitaxel, which is a microtubule stabilizer. The use of nanoparticle albumin-bound paclitaxel (nab-ptx) avoids hypersensitivity reactions due to the absence of solvent needed to dissolve paclitaxel and it can be administered at higher doses. The ABSOLUTE randomized phase-3 clinical trial showed the non-inferiority of the nab-ptx used every week compared to the solvent-based paclitaxel used every week. This review describes the current advancements of the use of nab-ptx in GC in preclinical and clinical study investigations. The possibility of combining nab-ptx with other medications to improve response of patients to their specific molecular needs will also be debated

Isolated Testicular Metastasis from Prostate Cancer

Prostatic adenocarcinoma is the most frequently diagnosed carcinoma in the male population; the most common sites of secondary lesions are nodes, bones, and lungs. We report the clinical case of a 58-year-old man presenting with a single metastasis in the left testis after a radical prostatectomy/lymphadenectomy for prostate cancer. CASE REPORT This clinical report focuses on a 58-year-old man with prostate cancer who developed an uncommon single metastasis in the left testis after radical surgery and adjuvant pelvic radiation therapy. CONCLUSIONS Prostate-specific antigen (PSA) levels are important in the follow-up of prostate cancer. At the same time, physical examination of all possible sites of metastasis and proper evaluation of all signs/symptoms are indispensable in the process of identifying recurrence and for the selection of patients undergoing adjuvant therapy