Raul Miguel Luque

Prostate cancer (PCa) is one of the leading causes of cancer-related death among men worldwide. Considerable efforts have been devoted to developing more effective therapeutic strategies for PCa, particularly for metastatic castration-resistant prostate cancer (mCRPC), wherein resistance to androgen-receptor pathway inhibition remains a major clinical challenge. G protein-coupled receptors (GPCRs), the largest family of cell surface signaling receptors, regulate numerous physiological and pathological processes and represent major therapeutic targets across multiple diseases, including cancer. In PCa, hormone- and inflammation-related GPCRs have emerged as key regulators of tumor initiation, progression, therapeutic resistance, and metastasis. Accordingly, understanding the contribution of GPCR signaling to PCa biology may reveal novel opportunities for therapeutic intervention, particularly in mCRPC. In this review, we summarize the current knowledge on the expression and function of GPCRs in PCa development, progression, and metastasis, highlighting their potential as therapeutic targets and discussing opportunities for drug development, combination therapies, and drug repurposing.

Pituitary tumours (PiTs) are a heterogeneous group of diseases of the anterior pituitary gland. While they are often described as rare diseases, the actual prevalence of these tumours is higher than commonly believed, accounting for at least 15% of all intracranial tumours. Yet, the high heterogeneity of the different PiTs (intra- and inter-patient heterogeneity), rooted in part in the intrinsic cellular diversity of the normal pituitary gland itself, has significantly limited the understanding of the biological mechanisms linked to their development, progression and aggressive behaviour. Like other cancer types, understanding the tumour microenvironment (TME) might help to better understand the pathophysiology of PiT cells beyond genetics, epigenetics, transcriptomics and proteomics and could constitute a personalized approach to dealing with these complex and heterogeneous endocrine-related tumours and to developing novel diagnostic, prognostic and future therapeutic tools. Importantly, the concept of TME relies on the notion that tumours are more than a group of tumour cells, but rather a heterogeneous mixture of tumour and non-tumour cells interacting with local components (growth factors, cytokines, etc.) within a remodelled tumour extracellular matrix (ECM). In this review, we will focus on describing the latest research on this complex TME–PiTs architecture network, which could bring a new era in diagnosing and treating these heterogeneous and complex endocrine-related cancers.

Objective: An SF3B1 (Somatic splicing factor 3B subunit 1) mutation has been associated with prolactin-secreting pituitary neuroendocrine tumours (PitNET) with increased proliferation, invasion, dopamine agonist resistance and reduced progression-free survival. Design: We screened a multi-centric cohort of 127 patients with prolactin-secreting PitNET for the SF3B1R625H mutation using digital PCR. Methods: A comparative analysis was conducted between wild-type and mutated tumours, assessing clinical parameters, including age at diagnosis, sex distribution, prolactin levels, tumour size, extent of invasion, recurrence, and response to dopamine agonists. Results: Somatic SF3B1R625H mutation was found in 21/127 patients (17%), who were diagnosed at a younger age (p=0.04) and had larger tumour diameter (p=0.03). Patients who needed transcranial surgery had a higher mutation frequency in their tumour samples compared to the transsphenoidal group (p=0.01). The occurrence of mutation was similar in males and females. Preoperative and postoperative prolactin levels were comparable in patients with mutant and wild-type tumours. No associations were observed between mutation and tumour invasiveness, Ki-67 proliferation index, p53 expression, recurrence and dopamine agonist resistance. Hypopituitarism at presentation, visual deficits, number of surgeries and disease-free survival were not different between the groups. Conclusion: SF3B1 somatic mutation status in lactotroph tumours—as assessed by digital PCR technology—is associated with a younger age at diagnosis and larger tumour diameter. However, in our cohort it does not appear to associate with histological features, higher recurrence, treatment resistance, tumour invasiveness, or long-term outcomes in our multi-centric cohort.

Prostate cancer (PCa) is a hormone-dependent tumor and one of the most prevalent cancers in men worldwide. PCa progression is influenced by its interaction

The 16th Acromegaly Consensus Conference in September 2024 updated recommendations on diagnosis and treatment of acromegaly comorbidities. Since the 2020 acromegaly comorbidity management guideline was published, new evidence has emerged on novel and known comorbidities and new treatment approaches. Forty-three experts in the management of acromegaly reviewed the current literature and assessed changes in clinical practice standards and management. Current outcome goals were considered and updated, with a focus on the impact of current and emerging treatments of these comorbidities. Participants assessed factors that determine pharmacological choices, as well as use of specific agents in the management of the most relevant acromegaly comorbidities. We present consensus recommendations highlighting optimization of evidence-based acromegaly comorbidities management.

Purpose: Inflammation is a key contributor to the pathogenesis and progression of heart failure (HF), correlating with increased morbidity and mortality. This study aimed to evaluate the molecular impact of a 24-week nutritional intervention on inflammasome-related components in HF patients, comparing a Mediterranean diet alone versus the same diet supplemented with hypercaloric, high-protein oral nutritional supplements (ONS) enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In a cohort of 38 patients, expression levels of inflammasome markers were assessed via microfluidic quantitative polymerase chain reaction (PCR) in peripheral blood mononuclear cells at baseline and post-intervention. Results: Some components, especially cytokines and apoptosis regulation components are overexpressed in patients with sarcopenia (NLRP1, NLRC4, CASP1, CASP5, CTSL, IFI16, TLR8, PSXR7, CCR1, CHUCK, MAPK14, CDKN1B). We observed a significant downregulation of Nod-like receptors NLRP12 and NLRP6, along with decreased expression of inflammasome activation components CASP5, TLR2, and TLR9 in the intervention group ( p < 0.05). Additionally, cytokines and inflammation-related molecules such as CXCR1, CXCR2, TGFB, CCL2, and NF-κB showed reduced expression, while the inhibitor CHUCK increased ( p < 0.05). Cell cycle regulators also shifted, with decreased CDKN2D expression ( p < 0.05), suggesting potential effects on cellular senescence and DNA repair pathways. Notably, these molecular changes were absent in patients adhering solely to the Mediterranean diet. Conclusions: these findings suggest that supplementing a Mediterranean diet with hypercaloric, high-protein, EPA and DHA-enriched ONS induces molecular modifications in inflammasome pathways associated with cardiac remodeling. Therefore, targeted nutritional strategies may offer a promising adjunct to improve cardiac function and disease progression in HF patients.