PROTACing the androgen receptor and other emerging therapeutics in prostate cancer.

INTRODUCTION: The androgen receptor (AR) is a critical driver of prostate cancer progression, and the advent of androgen receptor pathway inhibitors (ARPIs) has transformed the treatment landscape of metastatic prostate cancer. However, resistance to ARPIs eventually develops via mutations in AR, AR overexpression, and alternative AR signaling which have required novel approaches to target effectively. AREAS COVERED: The mechanism of action and early clinical results of proteolysis targeting chimera (PROTAC) agents targeting AR are reviewed. Preclinical and early clinical data for other emerging AR-targeting therapeutics, including dual-action androgen receptor inhibitors (DAARIs) and anitens that target the N-terminal domain of AR, were also identified through literature search for agents which may circumvent resistance through AR splice variants and AR ligand-binding domain mutations. The literature search utilized PubMed to identify articles that were relevant to this review from 2000 to 2024. EXPERT OPINION: PROTACs, DAARIs, and anitens represent novel and promising AR-targeting therapeutics that may become an important part of prostate cancer treatment in the future. Elucidating mechanisms of resistance, including ability of these agents to target full length AR, may yield further insights into maximal therapeutic efficacy aimed at silencing AR signaling.

Tumor Mutational Burden in Metastatic Castration-Resistant Prostate Cancer and Response to Checkpoint Inhibition.

This single-center cohort study assesses the association of tumor mutational burden status in patients with metastatic castration-resistant prostate cancer and response to immune checkpoint inhibitor therapy.

Immuno-Oncology Advances in Genitourinary Cancers.

Immuno-oncology (IO) has made monumental gains in the past decade in the genitourinary space. In this review, we highlight advances with IO in renal cell carcinoma where it now has become standard-of-care frontline therapy in the metastatic setting but also discuss challenges with the initial approach. In urothelial carcinoma, we discuss the growing use of IO including exciting recent updates with IO-based regimens that may soon become the new standard of care. We further discuss difficulties with IO in prostate cancer, germ cell tumors, and penile squamous cell carcinoma. Finally, we highlight advances in IO approaches beyond checkpoint inhibition including the role of the gut microbiome and T-cell redirecting therapies.

Novel Redirected T-Cell Immunotherapies for Advanced Prostate Cancer.

Immunotherapy has failed to achieve durable remissions in advanced prostate cancer patients. More potent T-cell-redirecting strategies may be needed to overcome the immunologically exclusive and suppressive tumor microenvironment. Clinical trials are underway, seeking to define the optimal target for T-cell redirection, such as PSMA, PSCA, or STEAP-1, as well as the optimal strategy, with CAR or bispecific antibodies. As results continue to emerge from these trials, understanding differential toxicity and efficacy of these therapies based on their targets and functional modifications will be key to advancing these promising therapies toward clinical practice. This review provides a unique depth and breadth of perspective regarding the diverse immunotherapy strategies currently under clinical investigation for men with advanced prostate cancer.

Review of treatments for generalized pustular psoriasis.

BACKGROUND: Generalized pustular psoriasis (GPP) is an uncommon variant of psoriasis that is characterized clinically by sterile pustule formation superimposed over inflamed, erythematous skin. METHODS: In June 2019, we conducted a systematic search of the PubMed Medline database using the keywords 'pustular psoriasis' and 'treatment'. RESULTS: First-line treatment for the condition consists of established therapies, such as acitretin, cyclosporine, methotrexate, and infliximab. Several medications targeting IL-17 or IL-23 have also emerged recently with drugs such as ixekizumab, secukinumab, brodalumab, guselkumab, and ustekinumab having shown some efficacy. CONCLUSIONS: This review highlights the research in support of common treatments of GPP, including classically used medications and newer monoclonal antibodies, and addresses the continued need for high quality studies regarding treatments for this condition.

Herpes associated erythema multiforme: A retrospective study.

BACKGROUND: Erythema multiforme (EM), an acute dermatologic condition frequently encountered in the Emergency Department, classically presents with a targetoid rash. We reviewed all recent EM cases seen at the LAC-USC County Hospital in order to ascertain the proportion of Herpes associated EM (HAEM) cases and to inform the diagnostic workup of these patients. METHODS: ICD-9 and ICD-10 codes were used to extract a list of EM cases at our institution from 2013 to 2019. Two non-blinded abstractors screened records to confirm an EM diagnosis and entered patient data utilizing a standardized data abstraction form. Cohen's kappa statistic was used to measure inter-rater reliability on various variables. Kappa (κ) values ranged from 0.803 to 1.0. RESULTS: 70 pediatric and 56 adult EM patients were included in the study. A likely etiology was ascribed to 63% of pediatric and adult EM cases. Pediatric EM was most commonly attributed to upper respiratory infection (URI) (n = 23; 33%), Mycoplasma pneumoniae infection (n = 5; 7%), and medications (n = 4; 6%). Adult EM was most commonly attributed to HSV infection (n = 11; 20%), medications (n = 5; 9%), URIs (n = 4; 7%), and other infections (n = 4; 7%). CONCLUSION: HSV-1/2 serologic testing should be considered in most EM patients to potentially prevent repeated ED visits. In EM cases not clearly attributable to herpes or drug exposure, physicians can consider further workup: Mycoplasma serology, nasal PCR, and a respiratory viral panel in pediatric patients. Identification of an etiologic cause may suggest a different treatment approach and prevent mislabeling of medication allergies in patient charts.