Search

Background The phase 3 CALGB 90203 (Alliance) trial evaluated neoadjuvant chemohormonal therapy for high-risk localized prostate cancer before radical prostatectomy. We dissected the molecular features of post-treated tumors with long-term clinical outcomes to explore mechanisms of response and resistance to chemohormonal therapy. Methods We evaluated 471 radical prostatectomy tumors, including 294 samples from 166 patients treated with 6 cycles of docetaxel plus androgen deprivation therapy before radical prostatectomy and 177 samples from 97 patients in the control arm (radical prostatectomy alone). Targeted DNA sequencing and RNA expression of tumor foci and adjacent noncancer regions were analyzed in conjunction with pathologic changes and clinical outcomes. Results Tumor fraction estimated from DNA sequencing was significantly lower in post-treated tumor tissues after chemohormonal therapy compared with controls. Higher tumor fraction after chemohormonal therapy was associated with aggressive pathologic features and poor outcomes, including prostate-specific antigen–progression-free survival. SPOP alterations were infrequently detected after chemohormonal therapy, while TP53 alterations were enriched and associated with shorter overall survival. Residual tumor fraction after chemohormonal therapy was linked to higher expression of androgen receptor–regulated genes, cell cycle genes, and neuroendocrine genes, suggesting persistent populations of active prostate cancer cells. Supervised clustering of post–treated high-tumor-fraction tissues identified a group of patients with elevated cell cycle–related gene expression and poor clinical outcomes.  Conclusions Distinct recurrent prostate cancer genomic and transcriptomic features are observed after exposure to docetaxel and androgen deprivation therapy. Tumor fraction assessed by DNA sequencing quantifies pathologic response and could be a useful trial endpoint or prognostic biomarker. TP53 alterations and high cell cycle transcriptomic activity are linked to aggressive residual disease, despite potent chemohormonal therapy. [ABSTRACT FROM AUTHOR]

Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69–0.93), with little heterogeneity between studies (I 2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy. [ABSTRACT FROM AUTHOR]

Since prostate cancer (PCa) was described as androgen-dependent, the androgen receptor (AR) has become the mainstay of its systemic treatment: androgen deprivation therapy (ADT). Although, through recent years, more potent drugs have been incorporated, this chronic AR signaling inhibition inevitably led the tumor to an incurable phase of castration resistance. However, in the castration-resistant status, PCa cells remain highly dependent on the AR signaling axis, and proof of it is that many men with castration-resistant prostate cancer (CRPC) still respond to newer-generation AR signaling inhibitors (ARSis). Nevertheless, this response is limited in time, and soon, the tumor develops adaptive mechanisms that make it again nonresponsive to these treatments. For this reason, researchers are focused on searching for new alternatives to control these nonresponsive tumors, such as: (1) drugs with a different mechanism of action, (2) combination therapies to boost synergies, and (3) agents or strategies to resensitize tumors to previously addressed targets. Taking advantage of the wide variety of mechanisms that promote persistent or reactivated AR signaling in CRPC, many drugs explore this last interesting behavior. In this article, we will review those strategies and drugs that are able to resensitize cancer cells to previously used treatments through the use of "hinge" treatments with the objective of obtaining an oncological benefit. Some examples are: bipolar androgen therapy (BAT) and drugs such as indomethacin, niclosamide, lapatinib, panobinostat, clomipramine, metformin, and antisense oligonucleotides. All of them have shown, in addition to an inhibitory effect on PCa, the rewarding ability to overcome acquired resistance to antiandrogenic agents in CRPC, resensitizing the tumor cells to previously used ARSis. [ABSTRACT FROM AUTHOR]

Introduction: Myocardial bridge is a morphological anomaly of the heart characterised by the presence of a myocardial segment above a coronary artery, which results in a higher risk of cardiovascular events. In patients with prostate cancer treated with androgen receptor-targeted agents, a higher risk of cardiotoxicity was observed. Case report: An 88 years old man with metastatic castration-resistant prostate cancer in treatment with enzalutamide, denosumab, and triptorelin presented to our attention complaining dyspnoea and angina pectoris. Management and outcome: Blood examinations revealed normal Troponin I levels. Transthoracic echocardiography revealed no signs of acute myocardial ischaemia. The treadmill stress test revealed S-T tract under levelling in V4–V6 with a very slow resolution. Coronary angiography identified a myocardial bridge in the medium tract of the interventricular anterior artery. Due to these findings, ranolazine and simvastatin were started and, after multidisciplinary assessment, we decided to continue the treatment with enzalutamide. At the first follow-up visit echocardiography found out the cardiological reports stability and no therapy changes were performed. During follow-up visit cardiological revaluation showed reports stability and no therapy changes were performed. Discussion: Due to the high prevalence of prostate cancer in elderly patients at high cardiovascular risk and the increasing use of androgen receptor-targeted agent, a multidisciplinary approach is highly recommended to weigh survival benefits on toxicities. This case report may support the use of androgen receptor-targeted agent in elderly patients with controlled cardiovascular diseases, a population that is often excluded from randomised trials. [ABSTRACT FROM AUTHOR]

Monoamine oxidase A (MAOA), a mitochondrial enzyme degrading biogenic and dietary amines, has been studied in the contexts of neuropsychiatry and neurological disorders for decades, but its importance in oncology, as best exemplified in prostate cancer (PC) to date, was only realized recently. PC is the most commonly diagnosed non-skin cancer and the second deadliest malignancy for men in the United States. In PC, the increased expression level of MAOA is correlated with dedifferentiated tissue microarchitecture and a worse prognosis. A wealth of literature has demonstrated that MAOA promotes growth, metastasis, stemness and therapy resistance in PC, mainly by increasing oxidative stress, augmenting hypoxia, inducing epithelial-to-mesenchymal transition, and activating the downstream principal transcription factor Twist1-dictated multiple context-dependent signaling cascades. Cancer-cell-derived MAOA also enables cancer-stromal cell interaction involving bone stromal cells and nerve cells by secretion of Hedgehog and class 3 semaphorin molecules respectively to modulate the tumor microenvironment in favor of invasion and metastasis. Further, MAOA in prostate stromal cells promotes PC tumorigenesis and stemness. Current studies suggest that MAOA functions in PC in both cell autonomous and non-autonomous manners. Importantly, clinically available monoamine oxidase inhibitors have shown promising results against PC in preclinical models and clinical trials, providing a great opportunity to repurpose them as a PC therapy. Here, we summarize recent advances in our understanding of MAOA roles and mechanisms in PC, present several MAOA-targeted strategies that have been nominated for treating PC, and discuss the unknowns of MAOA function and targeting in PC for future exploration.

Background: Androgen sensitivity, which was established as the leading etiology of androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH), plays an important role in SARS-CoV-2 infection. Vaccination is essential for AGA and BPH patients in view of the high risk from SARS-CoV-2 infection. Purpose: We aimed to investigate the associated factors for SARS-CoV-2 vaccination and its side effects in populations with AGA and BPH. Method: We collected the data on SARS-CoV-2 vaccination and adverse reactions of male AGA and BPH patients visited the outpatient of Xiangya hospital by telephone and web-based questionnaires. Vaccination rate and adverse reactions were compared by different vaccine types and use of antiandrogen therapy. Result: A total of 457 AGA patients and 397 BPH patients were recruited in this study. Among which, 92.8% AGA patients and 61.0% BPH patients had at least the first dose of SARS-CoV-2 vaccination (p < 0.001). Having comorbidities and use of anti-androgen therapy increased the risk of un-vaccination among AGA by 2.875 and 3.729 times, respectively (p < 0.001). Around 31.1% AGA patients and 9.5% BPH patients presented adverse reactions, which were mostly mild. Anti-androgen therapy increased the inclination of injection site pain after vaccination (18.7% vs 11.9%; OR: 1.708, 95% CI: 1.088-2.683, p = 0.019). Conclusion: Co-existence of other systemic diseases and anti-androgen therapy were the limiting factors for SARS-CoV-2 unvaccination, especially in AGA patients. The importance of SARS-CoV-2 vaccines should be strengthened and popularized in androgen sensitive phenotypes. [ABSTRACT FROM AUTHOR]

Extramammary Paget disease (EMPD) is a rare form of cutaneous, intraepithelial adenocarcinoma, which typically presents itself as an erythematous plaque originating from apocrine-gland rich regions, such as the vulva, the perianal region, the scrotum, the penis, or the axilla. EMPD patients typically have a good prognosis, with expected 5-year survival of 60%-92%, but it is estimated that about one-third of EMPD patients will develop lymph node or distant metastases. Treatment approaches for EMPD include locoregional therapies such as broad surgical resection, radiotherapy, or topical imiquimod, when the disease is localized, and chemotherapy and biological agents for advanced EMPD. We report the case of a 58-year-old man diagnosed with locally advanced, symptomatic HER2-overexpressing, AR-positive EMPD, who achieved long-term tumor control with a sequence of several trastuzumabbased treatments (more than 30 months with second-line carboplatin plus paclitaxel plus trastuzumab followed by trastuzumab maintenance; 9 months for third-line vinorelbine plus trastuzumab). Even if it is reported that AR expression occurs concomitantly with HER2 overexpression in more than half of the cases of EMPD, to the best of our knowledge, this is the first case report describing androgen receptor blockade therapy in combination with an anti-HER2 agent. Our patient did not benefit from androgen receptor blockade in combination with trastuzumab, thus suggesting that AR expression may simply reflect an intrinsic characteristic of the EMPD cell of origin, rather than tumor dependence upon AR signaling. Given the reported sensibility to anti-HER2 therapy, also new antibody drug conjugates targeting HER2 are worth exploring in the management of advanced EMPD. [ABSTRACT FROM AUTHOR]

Extramammary Paget disease (EMPD) is a rare form of cutaneous, intraepithelial adenocarcinoma, which typically presents itself as an erythematous plaque originating from apocrine-gland rich regions, such as the vulva, the perianal region, the scrotum, the penis, or the axilla. EMPD patients typically have a good prognosis, with expected 5-year survival of 60%–92%, but it is estimated that about one-third of EMPD patients will develop lymph node or distant metastases. Treatment approaches for EMPD include locoregional therapies such as broad surgical resection, radiotherapy, or topical imiquimod, when the disease is localized, and chemotherapy and biological agents for advanced EMPD. We report the case of a 58-year-old man diagnosed with locally advanced, symptomatic HER2-overexpressing, AR-positive EMPD, who achieved long-term tumor control with a sequence of several trastuzumab-based treatments (more than 30 months with second-line carboplatin plus paclitaxel plus trastuzumab followed by trastuzumab maintenance; 9 months for third-line vinorelbine plus trastuzumab). Even if it is reported that AR expression occurs concomitantly with HER2 overexpression in more than half of the cases of EMPD, to the best of our knowledge, this is the first case report describing androgen receptor blockade therapy in combination with an anti-HER2 agent. Our patient did not benefit from androgen receptor blockade in combination with trastuzumab, thus suggesting that AR expression may simply reflect an intrinsic characteristic of the EMPD cell of origin, rather than tumor dependence upon AR signaling. Given the reported sensibility to anti-HER2 therapy, also new antibody drug conjugates targeting HER2 are worth exploring in the management of advanced EMPD.

Since prostate cancer (PCa) was described as androgen-dependent, the androgen receptor (AR) has become the mainstay of its systemic treatment: androgen deprivation therapy (ADT). Although, through recent years, more potent drugs have been incorporated, this chronic AR signaling inhibition inevitably led the tumor to an incurable phase of castration resistance. However, in the castration-resistant status, PCa cells remain highly dependent on the AR signaling axis, and proof of it is that many men with castration-resistant prostate cancer (CRPC) still respond to newer-generation AR signaling inhibitors (ARSis). Nevertheless, this response is limited in time, and soon, the tumor develops adaptive mechanisms that make it again nonresponsive to these treatments. For this reason, researchers are focused on searching for new alternatives to control these nonresponsive tumors, such as: (1) drugs with a different mechanism of action, (2) combination therapies to boost synergies, and (3) agents or strategies to resensitize tumors to previously addressed targets. Taking advantage of the wide variety of mechanisms that promote persistent or reactivated AR signaling in CRPC, many drugs explore this last interesting behavior. In this article, we will review those strategies and drugs that are able to resensitize cancer cells to previously used treatments through the use of “hinge” treatments with the objective of obtaining an oncological benefit. Some examples are: bipolar androgen therapy (BAT) and drugs such as indomethacin, niclosamide, lapatinib, panobinostat, clomipramine, metformin, and antisense oligonucleotides. All of them have shown, in addition to an inhibitory effect on PCa, the rewarding ability to overcome acquired resistance to antiandrogenic agents in CRPC, resensitizing the tumor cells to previously used ARSis.

Male occult triple-negative breast cancer (TNBC) is an exceedingly rare form of breast cancer, and prospective information regarding its management is therefore lacking. Current treatment strategies are largely extrapolated from clinical trials of female breast cancer, leading to substantial knowledge gaps concerning the optimal management of male breast cancer. Here, we present a male patient with occult TNBC who responded to immunotherapy, with an obvious reduction in his tumor burden following antiandrogen therapy, after heavy treatment with several lines of chemotherapy. This case highlights the potential efficacy of immunotherapy in cases of male TNBC and suggests a role for antiandrogen therapy in managing patients with luminal androgen receptor-positive TNBC. [ABSTRACT FROM AUTHOR]

Male occult triple-negative breast cancer (TNBC) is an exceedingly rare form of breast cancer, and prospective information regarding its management is therefore lacking. Current treatment strategies are largely extrapolated from clinical trials of female breast cancer, leading to substantial knowledge gaps concerning the optimal management of male breast cancer. Here, we present a male patient with occult TNBC who responded to immunotherapy, with an obvious reduction in his tumor burden following antiandrogen therapy, after heavy treatment with several lines of chemotherapy. This case highlights the potential efficacy of immunotherapy in cases of male TNBC and suggests a role for antiandrogen therapy in managing patients with luminal androgen receptor-positive TNBC.

Enzalutamide combined with androgen deprivation therapy (ADT) significantly prolonged metastasis-free survival and overall survival (OS) versus ADT alone in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) with rapidly rising prostate-specific antigen (PSA). The objective of this post hoc analysis of the PROSPER trial is to evaluate OS benefit and safety of enzalutamide in patients across age and regional subgroups. Eligible men with nmCRPC, PSA doubling time ≤10 months and PSA ≥2 ng/mL with continued ADT use were randomised 2:1 to enzalutamide 160 mg or placebo. OS and safety were examined by age (<70 vs ≥70 years) and region (North America, Europe, Asia or the rest of the world). The impact of prior and subsequent therapy was also examined. In total, 1401 men were enrolled (median age, 74 years). Enzalutamide plus ADT reduced the risk of death, independent of age or region. Multivariate analyses identified Eastern Cooperative Oncology Group (ECOG) status (P < 0.0001), log (PSA; P = 0.0002) and subsequent therapy (P < 0.0001) as statistically significant factors impacting OS. Safety was consistent across age and regional subgroups. Any grade treatment-emergent adverse events were similar across age groups, were more common in the placebo group and had regional variation. In men with nmCRPC and rapidly rising PSA, the benefit and safety of enzalutamide were consistent across age and regional subgroups. Variables impacting OS included ECOG status, log (PSA) and subsequent therapy. NCT02003924. [Display omitted] • Enzalutamide plus androgen deprivation therapy reduced the risk of death in non-metastatic castration-resistant prostate cancer. • Overall survival with enzalutamide was similar across age and geographical regions. • Three factors were identified that improved overall survival. • The safety of enzalutamide was similar across age but varied with geography. [ABSTRACT FROM AUTHOR]

Aim: To provide an overview on the available treatments to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer.Methods: The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published and assessed the validity of the information on efficacy and treatment-related toxicity.Results: Eight randomized controlled trials and one meta-analysis were identified. Two randomized trials demonstrated that prophylactic radiation therapy (RT) using 1 × 10 Gy or 2 × 6 Gy significantly reduced the rate of gynecomastia but not breast pain, as compared to observation. A randomized dose-finding trial identified the daily dose of 20 mg tamoxifen (TMX) as the most effective prophylactic dose and another randomized trial described that daily TMX use was superior to weekly use. Another randomized trial showed that prophylactic daily TMX is more effective than TMX given at the onset of gynecomastia. Two other randomized trials described that TMX was clearly superior to anastrozole in reducing the risk for gynecomastia and/or breast pain. One comparative randomized trial between prophylactic RT using 1 × 12 Gy and TMX concluded that prophylactic TMX is more effective compared to prophylactic RT and furthermore that TMX appears to be more effective to treat gynecomastia and/or breast pain when symptoms are already present. A meta-analysis confirmed that both prophylactic RT and TMX can reduce the risk of gynecomastia and/or breast pain with TMX being more effective; however, the rate of side effects after TMX including dizziness and hot flushes might be higher than after RT and must be taken into account. Less is known regarding the comparative effectiveness of different radiation fractionation schedules and more modern RT techniques.Conclusions: Prophylactic RT as well as daily TMX can significantly reduce the incidence of gynecomastia and/or breast pain. TMX appears to be an effective alternative to RT also as a therapeutic treatment in the presence of gynecomastia but its side effects and off-label use must be considered. [ABSTRACT FROM AUTHOR]

Several steps in the transitioning process may affect sexual desire in transgender people. This is often underexposed by those providing gender-affirming care. To prospectively assess sexual desire during the first 3 years of hormonal therapy (HT) in transgender people. This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence. At baseline, different psychological questionnaires were administered. Sex steroids were measured at each follow-up visit. Data were analyzed cross-sectionally and prospectively. Prospective analysis of total, dyadic (with another person), and solitary (with oneself) sexual desire in 766 participants (401 transgender women [TW], 364 transgender men [TM]) was carried out using the Sexual Desire Inventory (SDI) questionnaire during a 3-year follow-up period, starting at the initiation of HT. Other factors associated with prospective changes were assessed. In TW, total, dyadic, and solitary SDI scores decreased during the first 3 months of HT. However, after 36 months, total and dyadic SDI scores were higher than baseline scores. Solitary scores after 36 months were comparable with baseline scores. In TM, total, dyadic, and solitary SDI scores increased over the first 3 months, remaining stable thereafter. However, total and dyadic SDI scores after 36 months were comparable with baseline scores, whereas solitary scores remained higher than baseline. Factors associated with a prospective increase in SDI scores included having undergone gonadectomy, no longer experiencing menstrual bleeding or higher gender dysphoria levels at baseline (in TM only). This study offers clear data on the time course of sexual desire after starting HT and thereby helps to inform people who want to start HT. Transgender people can be informed that changes in sexual desire after initiating HT are temporary. Over a longer period of time, the current research does not suggest induction of hypoactive sexual disorder in TW or long-term increased sexual desire in TM. Strengths include the prospective design of this large multicentric study, the well-defined cohort, controlling for HT, sex steroids, and other factors. Limitations include performing a data lock, the absence of an objective measure of sexual desire, and the timing of laboratory measurements. Gender-affirming HT only induces short-term changes in sexual desire in transgender people. Over a longer period of time, a net increase in dyadic sexual desire in TW receiving feminizing HT and sexual desire scores comparable with baseline in TM receiving virilizing HT, were observed. Defreyne J, Elaut E, Kreukels B, et al. Sexual Desire Changes in Transgender Individuals Upon Initiation of Hormone Treatment: Results From the Longitudinal European Network for the Investigation of Gender Incongruence Study. J Sex Med 2020;17:812–825. [ABSTRACT FROM AUTHOR]

Prostate cancer is a very common disease, which is, unfortunately, often the cause of many male deaths. This is underlined by the fact that the early stages of prostate cancer are often asymptomatic. Therefore, the disease is usually detected and diagnosed at late advanced or even metastasized stages, which are already difficult to treat. Hence, it is important to pursue research and development not only in terms of novel diagnostic methods but also of therapeutic ones, as well as to increase the effectiveness of the treatment by combinational medicinal approach. Therefore, in this review article, we focus on recent approaches and novel potential tools for the treatment of advanced prostate cancer; these include not only androgen deprivation therapy, antiandrogen therapy, photodynamic therapy, photothermal therapy, immunotherapy, multimodal therapy, but also poly(ADP-ribose) polymerase, Akt and cyclin-dependent kinase inhibitors.

Triple negative breast cancer (TNBC) represents the 15-20% of all breast cancers (BC) and is characterized by a very aggressive behavior. Recent data suggest that TNBC is not a single disease, but it is rather an umbrella for different ontology-profiles such as basal like 1 and 2, mesenchymal, and the luminal androgen receptor (LAR). The LAR subtype is characterized by the expression of the Androgen Receptor (AR) and its downstream effects. Notwithstanding the role of the AR in several signaling pathways, its impact on a biological and clinical standpoint is still controversial. The LAR subtype has been associated with better prognosis, less chemotherapy responsiveness and lower pathologic complete response after neoadjuvant treatment. Clinical evidence suggests a role for anti-androgen therapies such as bicalutamide, enzalutamide and abiraterone, offering an interesting chemo-free alternative for chemo-unresponsive patients, and therefore potentially shifting current treatment strategies. [ABSTRACT FROM AUTHOR]

Background Although research on the relation between testosterone and aggression in humans is inconclusive, guidelines (including the World Professional Association for Transgender Health Standards of Care, edition 7) have warned for an increase in aggression in transgender men taking testosterone treatment. Aims To investigate the association between levels of testosterone and aggression in treatment-seeking transgender people and explore the role of mental health psychopathology (anxiety and depressive symptoms) and social support in aggression in this population. Methods Every transgender person invited for assessment at a national transgender health clinic in the United Kingdom during a 3-year period (2012–2015) completed self-report measures for interpersonal problems, including levels of aggression (Inventory of Interpersonal Problems [IIP-32]), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), social support (Multidimensional Scale of Perceived Social Support), and experiences of transphobia before and 1 year after the initiation of gender-affirming hormonal therapy. Correlations between prospective scores for the IIP-32 factor “too aggressive” and prospective levels of sex steroids, prospective psychological (HADS), and baseline psychosocial measurements were tested. Outcomes Prospective scores for the factor “too aggressive” were not correlated to prospective serum testosterone levels. Results Results of 140 people (56 transgender men, 84 transgender women) were analyzed. A prospective increase in scores for the factor “too aggressive” of the IIP-32 in transgender men 1 year after being treated with testosterone treatment or a decrease of the IIP-32 aggression scores in transgender women 1 year after gender-affirming hormonal therapy was not found. However, a positive correlation was found between increasing HADS anxiety scores and increasing scores for the IIP-32 “too aggressive” score in the entire study population and a positive correlation with lower support from friends in transgender women. Clinical Implications Hormone-prescribing physicians can be reassured that the long-term administration of testosterone in transgender men does not increase aggressive behavior. Strengths and Limitations This is the 1st prospective study to assess the effect of gender-affirming hormonal care on aggression. Limitations included the use of different laboratories, the use of a patient-reported outcome measure, and the lack of aggression subtypes. Conclusions Testosterone therapy was not associated with an increase in levels of aggression in transgender men or a decrease in aggressive behavior in transgender women on antiandrogen and estrogen therapy, but other psychological and/or social factors, such as anxiety levels, appear to contribute to self-reported aggression in transgender people. Defreyne J, T'Sjoen G, Bouman WP, et al. Prospective Evaluation of Self-Reported Aggression in Transgender Persons. J Sex Med 2018;15:768–776. [ABSTRACT FROM AUTHOR]

Abstract: Triple negative breast cancer (TNBC) is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. It also has a distinct epidemiology. TNBCs are frequently of high histologic grade, typically more aggressive and difficult to treat than hormone receptor‐positive tumors, and they are associated with a higher risk of early relapse with visceral metastasis after surgery, chemotherapy and/or radiotherapy. The lack of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression precludes the use of targeted therapies in advanced stages, and the only approved systemic treatment option is chemotherapy with or without bevacizumab. In patients with advanced TNBC, responses to chemotherapy occur, but are often of short duration and it is associated with poor prognosis. The median overall survival for patients with metastatic TNBC is about 9–12 months with conventional cytotoxic agents. Given the suboptimal outcomes with chemotherapy, new targeted therapies for TNBC are urgently needed. This review summarizes the clinical efficacy, perspectives and future challenges of using new treatment options for metastatic TNBC, such as poly‐ADP‐ribose‐polymerase inhibitors, antiandrogen therapies and immune checkpoint inhibitors (antiprogrammed death receptor‐1/PD‐L1 monoclonal antibodies). [ABSTRACT FROM AUTHOR]

Background: Numerous studies have substantiated the association between aging and the progression of malignant tumors in humans, notably prostate cancer (PCa). Nevertheless, to the best of our knowledge, no studies have comprehensively elucidated the intricate characteristics of the aging microenvironment (AME) in PCa. Methods: AME regulatory patterns were determined using the NMF algorithm. Then an ageing microenvironment index (AMI) was constructed, with excellent prognostic and immunotherapy prediction ability, and its' clinical relevance was surveyed through spatial transcriptomics. Further, the drug response was analysed using the Genomics of Drug Sensitivity in Cancer (GDSC), the Connectivity Map (CMap) and CellMiner database for patients with PCa. Finally, the AME was studied using in vitro and vivo experiments. Results: Three different AME regulatory patterns were identified across 813 PCa patients, associated with distinct clinical prognosis and physiological pathways. Based on the AMI, patients with PCa were divided into the high-score and low-score subsets. Higher AMI score was significantly infiltrated with more immune cells, higher rate of biochemical recurrence (BCR) and worse response to immunotherapy, antiandrogen therapy and chemotherapy in PCa. In addition, we found that the combination of bicalutamide and embelin was capable of suppressing tumor growth of PCa. Besides, as the main components of AMI, COL1A1 and BGLAP act as oncogenes and were verified via in vivo and in vitro experiments. Conclusions: AME regulation is significantly associated with the diversity and complexity of TME. Quantitative evaluation of the AME regulatory patterns may provide promising novel molecular markers for individualised therapy in PCa., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Prostate cancer is initially responsive to androgen deprivation therapy, but most patients eventually develop castration-resistant disease. Enzalutamide is an androgen receptor (AR) inhibitor that targets several steps in the AR signaling pathway and has shown significant efficacy in the treatment of metastatic castration-resistant prostate cancer in patients with or without prior chemotherapy. To provide optimal treatment, it is important to understand the implications of enzalutamide use in the context of other therapies, as recent findings have suggested cross-resistance occurs between and within drug classes. Mutations and splice variants of AR also impact the course of prostate cancer. Future strategies involving enzalutamide should account for previous exposure to taxanes or antiandrogen therapies and the presence of AR variants that could affect efficacy. [ABSTRACT FROM AUTHOR]

Monoamine oxidase A (MAOA), a mitochondrial enzyme degrading biogenic and dietary amines, has been studied in the contexts of neuropsychiatry and neurological disorders for decades, but its importance in oncology, as best exemplified in prostate cancer (PC) to date, was only realized recently. PC is the most commonly diagnosed non-skin cancer and the second deadliest malignancy for men in the United States. In PC, the increased expression level of MAOA is correlated with dedifferentiated tissue microarchitecture and a worse prognosis. A wealth of literature has demonstrated that MAOA promotes growth, metastasis, stemness and therapy resistance in PC, mainly by increasing oxidative stress, augmenting hypoxia, inducing epithelial-to-mesenchymal transition, and activating the downstream principal transcription factor Twist1-dictated multiple context-dependent signaling cascades. Cancer-cell-derived MAOA also enables cancer-stromal cell interaction involving bone stromal cells and nerve cells by secretion of Hedgehog and class 3 semaphorin molecules respectively to modulate the tumor microenvironment in favor of invasion and metastasis. Further, MAOA in prostate stromal cells promotes PC tumorigenesis and stemness. Current studies suggest that MAOA functions in PC in both cell autonomous and non-autonomous manners. Importantly, clinically available monoamine oxidase inhibitors have shown promising results against PC in preclinical models and clinical trials, providing a great opportunity to repurpose them as a PC therapy. Here, we summarize recent advances in our understanding of MAOA roles and mechanisms in PC, present several MAOA-targeted strategies that have been nominated for treating PC, and discuss the unknowns of MAOA function and targeting in PC for future exploration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen and Wu.)