Management of Metastatic Prostate Cancer.

Background: Advanced stages of prostate cancer (PCa), in particular metastatic castration-resistant prostate cancer (mCRPC), are associated with significant morbidity and mortality. The androgen receptor (AR) signaling pathway is a cornerstone of therapeutic intervention, but resistance mechanisms and disease progression demand increasingly complex treatment strategies.

Methods: This narrative review is based on expert consensus, supported by a literature search in PubMed (MEDLINE) and the abstract databases of ASCO, ASCO GU and ESMO.

Anticancer activity of triterpene glycosides from the sea star Solaster pacificus.

Marine triterpene glycosides are known to exhibit significant anticancer activity. We investigated pacificusoside C and cucumariosides C and C isolated from a sea star Solaster pacificus in prostate cancer models with varying drug resistance and in non-cancerous cells in vitro. Cucumarioside C showed selectivity comparable to cisplatin, whereas the other compounds were less selective.

Years of Life Lost in Metastatic and Locally Advanced Prostate Cancer.

Background And Objective: Prostate cancer (PCa) is the second most common cancer-specific cause of death in the USA. However, the effects of metastatic or locally advanced PCa on individual years of life lost (YLL) have not been addressed.

Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database 2004-2021, metastatic (cM1) and locally advanced (cT3/4, cN1) PCa patients aged 45-75 yr were included.

Debate 3: Oligometastatic Hormone Sensitive Prostate Cancer Management: Systemic Therapy Approach.

Oligometastatic prostate cancer (OMPC) represents an intermediate stage between localized and extensive metastatic disease, characterized by a limited number of metastatic lesions. While metastasis-directed therapy (MDT) has gained traction for its potential to delay systemic therapy, systemic therapy itself is falling behind. In our view, this is not appropriate at the current stage.

[Androgen receptor-targeted therapies - avoid clinically relevant interactions].

Pharmacotherapy of older patients requires special attention to drug interactions, based on an increase in morbidity and elevated need for polypharmacy. Especially for drugs with a narrow therapeutic index, interactions may require dose adjustments, discontinuation or switching of co-medication. These interactions are frequently based on pharmacokinetic alterations of drug metabolism via the cytochrome P450 (CYP) enzyme system, mainly via CYP3A4.

First-in-Human Serum Stability Studies of [Lu]Lu-AMTG: A Step Toward Improved GRPR-Targeted Radiopharmaceutical Therapy.

The use of PET/CT with gastrin-releasing peptide receptor (GRPR) ligand [Ga]Ga-AMTG has recently been shown to diagnose metastatic disease not detected by F-PSMA PET/CT in patients with metastatic castration-resistant prostate cancer. This study aimed to analyze the serum stability of [Lu]Lu-AMTG in human subjects due to the compound's high stability observed preclinically and to elucidate its therapeutic potential. Blood samples were collected at various time points after intravenous injection of 7.

6-[(1,4-Naphthoquinone-2-yl)methyl]thio-Glucose Conjugates, a Novel Targeted Approach for Advanced Prostate Cancer.

The Warburg effect is a shift from oxidative phosphorylation to anaerobic glycolysis, accompanied by an enormous increase in glucose uptake into cancer cells. We have utilized this effect to design a new group of targeted 1,4-naphthoquinone-glucose derivatives conjugated with a novel thiomethylene linker that are cytotoxic to prostate cancer cells. Compound PeS-9 revealed the highest efficacy and selectivity, which was conditioned by a GLUT-1-mediated uptake.

Transcriptional profiles of circulating tumor cells reflect heterogeneity and treatment resistance in advanced prostate cancer.

Purpose: New biomarkers for the detection and monitoring of aggressive variant prostate cancer (AVPC) including therapy-induced neuroendocrine prostate cancer (NEPC) are urgently needed, as measuring prostate-specific antigen (PSA) is not reliable in androgen-indifferent diseases. Molecular analysis of circulating tumor cells (CTC) enables repeated analysis for monitoring and allows to capture the heterogeneity of the disease.

Experimental Design: 102 blood samples from 76 metastatic prostate cancer (mPC) patients, including 37 samples from histologically proven NEPC, were collected and CTCs were enriched using label-dependent and label-independent methods.

[Aggressive variant prostate cancer and transdifferentiated neuroendocrine prostate cancer: from diagnosis to therapy].

Aggressive variants of prostate cancer (AVPC) comprise a heterogeneous group of prostate carcinomas characterized by androgen-independent, aggressive tumor growth. Clinically, they are characterized by prostate-specific antigen (PSA)-negative progression and an atypical metastatic pattern with increased visceral and osteolytic metastasis. Based on immunohistochemistry and transcriptome profiling, AVPC are divided into four subgroups: neuroendocrine prostate cancer (NEPC), amphicrine prostate cancer, androgen receptor-low expressing prostate cancer and double-negative prostate cancer.

Incisional PSMA PET/CT-positive recurrences in prostate cancer- is there an implication on clinical care?

Oligorecurrent prostate cancer (PCa) can be treated with metastasis-directed therapy (MDT), which may be performed using radioguided surgery (RGS) as an experimental approach. These procedures have shown promising outcomes, largely due to the high lesion detection rate of positron emission tomography/computed tomography (PET/CT). We present a case series of patients who underwent RGS following robot-assisted radical prostatectomy (RARP).

Stonikacidin A, an Antimicrobial 4-Bromopyrrole Alkaloid Containing L-Idonic Acid Core from the Northwestern Pacific Marine Sponge .

Stonikacidin A (), the first representative of a new class of 4-bromopyrrole alkaloids containing an aldonic acid core, was isolated from the marine sponge . The compound is named in honor of Prof. Valentin A.

[Paradigm shift in systemic therapy for metastatic urothelial carcinoma-antibody-drug conjugates (ADCs) and fibroblast growth factor receptor (FGFR) inhibitors].

Background: Patients with locally advanced or metastatic urothelial carcinoma face a poor prognosis. Standard first-line treatment involves platinum-based combinations followed by avelumab maintenance therapy. Follow-up therapies include enfortumab vedotin, vinflunine, and taxanes.

Lectins CGL and MTL, representatives of mytilectin family, exhibit different antiproliferative activity in Burkitt's lymphoma cells.

Lectins are carbohydrate-binding proteins, whose biological effects are exerted via binding to glycoconjugates expressed on the surface of cells. Exposure to lectins can lead not only to a change in the structure and properties of cells but also to their death. Here, we studied the biological activity of lectins from the mussels Crenomytilus graynus (CGL) and Mytilus trossulus (MTL) and showed that these proteins can affect the proliferation of human lymphoma cells.

Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2.

While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers.

Limited prognostic role of routine serum markers (AP, CEA, LDH and NSE) in oligorecurrent prostate cancer patients undergoing PSMA-radioguided surgery.

Introduction: We evaluated the prognostic role of pre-salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) serum levels of alkaline phosphatase (AP), carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), and neuron-specific enolase (NSE).

Materials And Methods: Patients who consecutively underwent PSMA-RGS for prostate cancer (PCa) oligorecurrence between January 2019 and January 2022 were selected. Biomarkers were assessed one day before surgery.

[Molecular testing of prostate cancer: timing, methods and consequences].

Metastatic prostate cancer is a heterogeneous disease. To date, however, treatment decisions are often based on the extent and symptom burden of the tumour, concomitant diseases, and the patient's wishes. Molecular pathology aspects are rarely taken into account.

[Advanced renal cell carcinoma - an overview of current systemic therapy].

Renal cell carcinoma (RCC) is one of the more common tumor diseases in older adults. The only curative treatment method is surgical resection in the localized stage. Based on current study data, drug (combination) therapy in the metastatic stage is the most effective treatment option for non-resectable/metastatic RCC (mRCC).

Anticancer Activity of the Marine Triterpene Glycoside Cucumarioside A-2 in Human Prostate Cancer Cells.

Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), treatment is inevitably hampered by the development of drug resistance. Thus, new drugs are urgently needed. We investigated the efficacy, toxicity, and mechanism of action of the marine triterpene glycoside cucumarioside A-2 (CA-2) using an in vitro CRPC model.

PSMA PET-directed surgical metastasis-directed therapy in metachronous prostate cancer.

We present the case of a patient who underwent an open radical prostatectomy with pelvic lymph node dissection (Gleason 4+3, pT3a pN1 R0) in March 2017. In November 2020, prostate-specific membrane antigen (PSMA)-radioguided salvage lymph node dissection was planned due to a single left para-rectal lymph node at a [Ga] Ga-PSMA-I&T PET. In January 2022, the [Ga] Ga-PSMA-I&T PET showed an isolated liver lesion.

[Metastatic castration-resistant prostate cancer-emerging trends in therapy].

Background: An increasing understanding of the cellular processes involved in growth, metastasis and development of resistance enable the development of new treatment strategies for advanced prostate cancer.

Objectives: Using selected examples, the aim of this report is to present current developments to the reader and to give an outlook on possible upcoming changes in the treatment of advanced prostate cancer.

Materials And Methods: Narrative report based on expert consensus, supported by a literature search in PubMed (MEDLINE) and the abstract databases of the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO).

Preclinical Comparison of the Cu- and Ga-Labeled GRPR-Targeted Compounds RM2 and AMTG, as Well as First-in-Humans [Ga]Ga-AMTG PET/CT.

Despite the recent success of prostate-specific membrane antigen (PSMA)-targeted compounds for theranostic use in prostate cancer (PCa), alternative options for the detection and treatment of PSMA-negative lesions are needed. We have recently developed a novel gastrin-releasing peptide receptor (GRPR) ligand with improved metabolic stability, which might improve diagnostic and therapeutic efficacy and could be valuable for PSMA-negative PCa patients. Our aim was to examine its suitability for theranostic use.