Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target.

Prostate cancer (PCa) is the second most common cancer among men worldwide. The main screening tool remains the prostate-specific antigen (PSA), which shows significant limitations, including poor sensitivity/specificity. Therefore, establishing accurate non-invasive diagnostic biomarkers remains an unmet clinical need in PCa.

The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.

Breast cancer (BCa) is a highly prevalent pathological condition (̴30% in women) with limited and subtype-dependent prognosis and therapeutic options. Therefore, BCa management might benefit from the identification of novel molecular elements with clinical potential. Since splicing process is gaining a great relevance in cancer, this work analysed the expression of multiple Spliceosome Components (SCs = 17) and Splicing Factors (SFs = 26) and found a drastic dysregulation in BCa (n = 69) vs.

SRSF6 modulates histone-chaperone HIRA splicing to orchestrate AR and E2F activity in prostate cancer.

Despite novel therapeutic strategies, advanced-stage prostate cancer (PCa) remains highly lethal, pointing out the urgent need for effective therapeutic strategies. While dysregulation of the splicing process is considered a cancer hallmark, the role of certain splicing factors remains unknown in PCa. This study focuses on characterizing the levels and role of SRSF6 in this disease.

Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer.

Therapies that abrogate persistent androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC) remain an unmet clinical need. The N-terminal domain of the AR that drives transcriptional activity in CRPC remains a challenging therapeutic target. Herein we demonstrate that BCL-2-associated athanogene-1 (BAG-1) mRNA is highly expressed and associates with signaling pathways, including AR signaling, that are implicated in the development and progression of CRPC.

Dysregulation of RNA-Exosome machinery is directly linked to major cancer hallmarks in prostate cancer: Oncogenic role of PABPN1.

Novel biomarkers and therapeutic strategies for prostate-cancer (PCa) are required to overcome its lethal progression. The dysregulation/implication of the RNA-Exosome-complex (REC; cellular machinery controlling the 3'-5'processing/degradation of most RNAs) in different cancer-types, including PCa, is poorly known. Herein, different cellular/molecular/preclinical approaches with human PCa-samples (tissues and/or plasma of 7 independent cohorts), and in-vitro/in-vivo PCa-models were used to comprehensively characterize the REC-profile and explore its role in PCa.

Metformin and simvastatin exert additive antitumour effects in glioblastoma via senescence-state: clinical and translational evidence.

Background: Glioblastoma is one of the most devastating and incurable cancers due to its aggressive behaviour and lack of available therapies, being its overall-survival from diagnosis ∼14-months. Thus, identification of new therapeutic tools is urgently needed. Interestingly, metabolism-related drugs (e.

Somatostatin, Cortistatin and Their Receptors Exert Antitumor Actions in Androgen-Independent Prostate Cancer Cells: Critical Role of Endogenous Cortistatin.

Somatostatin (SST), cortistatin (CORT), and their receptors (SSTR1-5/sst5TMD4-TMD5) comprise a multifactorial hormonal system involved in the regulation of numerous pathophysiological processes. Certain components of this system are dysregulated and play critical roles in the development/progression of different endocrine-related cancers. However, the presence and therapeutic role of this regulatory system in prostate cancer (PCa) remain poorly explored.

Tumor suppressor role of RBM22 in prostate cancer acting as a dual-factor regulating alternative splicing and transcription of key oncogenic genes.

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths among men. Consequently, the identification of novel molecular targets for treatment is urgently needed to improve patients' outcomes. Our group recently reported that some elements of the cellular machinery controlling alternative-splicing might be useful as potential novel therapeutic tools against advanced PCa.

Alternative splicing in bladder cancer: potential strategies for cancer diagnosis, prognosis, and treatment.

Bladder cancer is the most common malignancy of the urinary tract worldwide. The therapeutic options to tackle this disease comprise surgery, intravesical or systemic chemotherapy, and immunotherapy. Unfortunately, a wide number of patients ultimately become resistant to these treatments and develop aggressive metastatic disease, presenting a poor prognosis.

Spliceosomic dysregulation unveils NOVA1 as a candidate actionable therapeutic target in pancreatic neuroendocrine tumors.

Dysregulation of the splicing machinery is emerging as a hallmark in cancer due to its association with multiple dysfunctions in tumor cells. Inappropriate function of this machinery can generate tumor-driving splicing variants and trigger oncogenic actions. However, its role in pancreatic neuroendocrine tumors (PanNETs) is poorly defined.

Prostate-Specific Membrane Antigen Expression and Response to DNA Damaging Agents in Prostate Cancer.

Purpose: Prostate-specific membrane antigen (PSMA) targeting therapies such as Lutetium-177 (177Lu)-PSMA-617 are affecting outcomes from metastatic castration-resistant prostate cancer (mCRPC). However, a significant subset of patients have prostate cancer cells lacking PSMA expression, raising concerns about treatment resistance attributable at least in part to heterogeneous PSMA expression. We have previously demonstrated an association between high PSMA expression and DNA damage repair defects in mCRPC biopsies and therefore hypothesized that DNA damage upregulates PSMA expression.

Dysregulation of the miRNome unveils a crosstalk between obesity and prostate cancer: miR-107 asa personalized diagnostic and therapeutic tool.

Prostate-specific antigen (PSA) is the gold-standard marker to screen prostate cancer (PCa) nowadays. Unfortunately, its lack of specificity and sensitivity makes the identification of novel tools to diagnose PCa an urgent medical need. In this context, microRNAs (miRNAs) have emerged as potential sources of non-invasive diagnostic biomarkers in several pathologies.

SF3B1 inhibition disrupts malignancy and prolongs survival in glioblastoma patients through BCL2L1 splicing and mTOR/ß-catenin pathways imbalances.

Background: Glioblastoma is one of the most devastating cancer worldwide based on its locally aggressive behavior and because it cannot be cured by current therapies. Defects in alternative splicing process are frequent in cancer. Recently, we demonstrated that dysregulation of the spliceosome is directly associated with glioma development, progression, and aggressiveness.

Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer.

Despite major improvements in the management of advanced prostate cancer over the last 20 years, the disease remains invariably fatal, and new effective therapies are required. The development of novel hormonal agents and taxane chemotherapy has improved outcomes, although primary and acquired resistance remains problematic. Inducing cancer cell death via apoptosis has long been an attractive goal in the treatment of cancer.

Dysregulated splicing factor SF3B1 unveils a dual therapeutic vulnerability to target pancreatic cancer cells and cancer stem cells with an anti-splicing drug.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, requiring novel treatments to target both cancer cells and cancer stem cells (CSCs). Altered splicing is emerging as both a novel cancer hallmark and an attractive therapeutic target. The core splicing factor SF3B1 is heavily altered in cancer and can be inhibited by Pladienolide-B, but its actionability in PDAC is unknown.

A New Old Target: Androgen Receptor Signaling and Advanced Prostate Cancer.

Owing to the development of multiple novel therapies, there has been major progress in the treatment of advanced prostate cancer over the last two decades; however, the disease remains invariably fatal. Androgens and the androgen receptor (AR) play a critical role in prostate carcinogenesis, and targeting the AR signaling axis with abiraterone, enzalutamide, darolutamide, and apalutamide has improved outcomes for men with this lethal disease. Targeting the AR and elucidating mechanisms of resistance to these agents remain central to drug development efforts.

Role of metformin and other metabolic drugs in the prevention and therapy of endocrine-related cancers.

Metabolic syndrome is associated with chronic diseases, including type 2 diabetes, cardiovascular diseases, and cancer. This review summarizes the current evidence on the antitumor effects of some relevant drugs currently used to manage metabolic-related pathologies (i.e.

Clinical, Cellular, and Molecular Evidence of the Additive Antitumor Effects of Biguanides and Statins in Prostate Cancer.

Context: Prostate cancer (PCa) is one of the leading causes of cancer-related death among the male population worldwide. Unfortunately, current medical treatments fail to prevent PCa progression in a high percentage of cases; therefore, new therapeutic tools to tackle PCa are urgently needed. Biguanides and statins have emerged as antitumor agents for several endocrine-related cancers.