New perspective in the management of neuroendocrine differentiation in prostate adenocarcinoma

In this review, we will present some of the information that is known about neuroendocrine (NE) cells and differentiation in the prostate. We will then speculate on the potential role that NE differentiation in prostate carcinoma may play and how this differentiation may be clinically analysed and treated. The androgen-independent growth of prostate cancer can be caused by different mechanisms; one of these is receptor-specific paracrine or autocrine growth modulation of human prostatic cancer cells by neuropeptides secreted by NE cells. Our results affirm that different methods of androgen deprivation can influence the serum chromogranin A (CgA) levels to different extents in prostate cancer. In particular, bicalutamide produces a significantly lower increase in serum CgA compared with castration therapy. In the light of other evidence that supports a significant relationship between serum CgA levels, tissue CgA expression and NE activity, we hypothesise that bicalutamide may reduce the risk of NE cell hyperactivation in prostate cancer. It is important to determine whether increases in CgA levels and NE cell activation are associated with progression towards hormone-independent prostate cancer. We recently proposed as therapy of NE activation in hormone-independent prostate cancer, a combination of oestrogens and somatostatin analogues. The combination of ethinyl estradiol and lanreotide had a favourable toxicity profile, offered objective and symptomatic responses in patients with limited treatment options and refractoriness to conventional hormonal therapy strategies and, in particular, offered a median overall survival that was superior to the 10-month median survival in patients with hormone refractory disease. This combination therapy also sustains the novel concept in cancer treatment in which therapies may target not only cancer cells but also its microenvironment in combination, which can confer protection from apoptosis.     

Noncanonical Wnt as a prognostic marker in prostate cancer: “you can’t always get what you Wnt”

ABSTRACT

Introduction: Wnt signaling is important for normal development, cell proliferation, and cell differentiation. However, aberrations in the pathway can lead to tumorigenesis and cancer progression. Recent genome-wide studies have demonstrated the frequent occurrence of Wnt pathway alterations in prostate cancer. Although alterations in the canonical Wnt pathway in prostate cancer may have an impact on prognosis, recent studies suggest that the noncanonical Wnt pathway also plays an important role in disease progression and treatment resistance.

Areas covered: We review the literature with regard to the potential prognostic significance of noncanonical Wnt signaling in prostate cancer. After a brief overview of the canonical and noncanonical Wnt pathways, we discuss the preclinical and clinical evidence for activation of Wnt signaling in prostate cancer. We focus on clinical evidence for noncanonical Wnt pathway components to serve as potential prognostic biomarkers.

Expert opinion: Although many therapeutic options are available for men with prostate cancer, there remains an unmet need for prognostic and predictive biomarkers to precisely guide clinical management. Early evidence suggests that components of the noncanonical Wnt pathway may serve as prognostic biomarkers. However, prospective validation studies are necessary before these biomarkers can be routinely applied in the clinic.     

Changing the Goal Posts: Prostate-specific Membrane Antigen Targeted Theranostics in Prostate Cancer

ObjectiveProstate-specific membrane antigen (PSMA) theranostics is changing the face of prostate cancer diagnosis and therapy. PSMA, a transmembrane protein over-expressed in many prostate cancers, is a promising target for theranostics. Theranostics is the concept of small molecule proteins that are labelled to different radionuclides and can be used for either diagnosis or therapy, dependent on whether they are labelled with an imaging or therapy radionuclide. By directly targeting the cancer cells with imaging and then for therapy, this approach embodies the philosophy of precision medicine – right drug, right time, right dose. The question is how to best utilise these new imaging and therapy agents in clinical practice. This review will evaluate the importance of PSMA in prostate cancer, its role in diagnostic imaging, and its potential as a therapy of advanced prostate cancer.Data SourcesElectronic databases including MEDLINE, Scopus, professional websites were searched.ConclusionPSMA-directed theranostics has an expanding role in prostate cancer because of its utility as a sensitive diagnostic tool that can be coupled with efficacious and low-toxicity therapeutic options. Ongoing research is required to determine how to use this effective tool for best patient care.Implications for Nursing PracticePSMA theranostics is rapidly being incorporated into the routine care of men with prostate cancer. Understanding its strengths, its limitations, and where it may be valuable in clinical care is important in undertaking best patient practice.     

Dealing with a troublesome body: A qualitative interview study of men’s experiences living with prostate cancer treated with endocrine therapy

PurposeEndocrine therapy for prostate cancer causes substantial side effects, and previous studies have focused on the impacts on sexuality and masculinity. Little is known about how men experience bodily alterations in everyday life through the course of the prostate cancer and treatment. The aim of this study was to show how men with prostate cancer experience bodily changes and how these alterations influence daily life.MethodThe study was conducted via qualitative interviews with a phenomenological hermeneutic approach. We interviewed ten men (aged 58–83) with prostate cancer who received endocrine therapy as the primary treatment method.ResultsThe results showed that five themes were important for the men’s experiences of their bodily alterations throughout the course of the illness: “something is ‘wrong’”, “when the body becomes troublesome”, “to be well or to be ill”, “dealing with the alterations” and “to talk about cancer and the intimate details”. Initially, the shock of receiving a cancer diagnosis and the physical changes in their bodies were at the forefront of many patients’ minds. Eventually, the impact of the side effects became more evident, which caused problems in everyday life. Yet, the men were able to reflect on the impact of treatment on their everyday lives.ConclusionThis study showed that hormone treatment has a significant influence, both directly and indirectly, on the bodies of prostate cancer patients. The experiences of men with prostate cancer may lead to feelings of loss of identity on an existential level.     

基于基因组学的前列腺癌临床精准诊疗研究进展

前列腺癌是男性最常见的癌症类型,高居美国男性癌症死亡原因第二位。癌症基因组高通量测序的兴起使得前列腺癌的分子分型成为了可能。将基础研究成果转化为临床上有实际应用价值的生物学标志物是目前前列腺癌精准诊治的关键。因此,本文就近年来基于基因组学的前列腺癌分子分型及临床精准诊治研究进展作一综述,以切实提高前列腺癌诊治水平。     

Men, culture and hegemonic masculinity: understanding the experience of prostate cancer

Following a diagnosis of, and treatment for prostate cancer, there is an expectation that men will cope with, adjust to and accept the psychosocial impact on their lives and relationships. Yet, there is a limited qualitative world literature investigating the psychosocial experience of prostate cancer, and almost no literature exploring how masculinity mediates in such an experience. This paper will suggest that the experience of prostate cancer, the process by which it is investigated, and the way in which it is understood has been shaped by an essentialist interpretation of gender, exemplified by hegemonic masculinity as the archetypal mechanism of male adaptation. In response to this static and limiting view of masculinity, this paper will offer a reframe of hegemonic masculinity. This reframe, being more aligned with common experience, will portray masculinity as a dynamic and contextual construct, better understood as one of a number of cultural reference points around which each man organises and adopts behaviour. It will be suggested that the extant literature, in being organised around hegemonic masculinity, obfuscates the experience of prostate cancer and acts to render covert any collateral masculinities, public or private, that may also be operating.     

前列腺癌尿液肿瘤标志物的研究进展

前列腺癌是男性生殖系统最常见的恶性肿瘤之一,也是导致男性癌症死亡的第五大原因,早期诊治可改善患者预后。目前,前列腺癌的诊断主要依赖于直肠指诊或血清前列腺特异性抗原(prostate specific antigen,PSA)检测后前列腺穿刺活检确诊。但血清PSA检测特异性较低,不能有效区分惰性前列腺癌与具有临床意义的前列腺癌,导致不必要的活检及过度治疗,因此迫切需要更具特异性的肿瘤标志物。前列腺癌细胞可将肿瘤标志物释放至前列腺液中,而后进入尿液,因此通过尿液即可检测前列腺癌肿瘤标志物。近年来,已开发了多种基于尿液及其外泌体的肿瘤标志物,如PSA、PCA3、MALAT1及微RNA等,本文将阐述尿液肿瘤标志物在前列腺癌诊断中的研究进展。     

Risk of metabolic syndrome, cardiovascular disease, and diabetes in androgen deprivation therapy

Men with prostate cancer may be at increased risk for metabolic syndrome, cardiovascular disease, and diabetes from androgen deprivation therapy (ADT). This article reviews current literature related to potential adverse effects of using ADT for localized prostate cancer. The use of gonadotropin-releasing hormone agonist therapy for prostate cancer in the early 1990s compared to the late 1990s is addressed. Oncology nurses play an important role in educating men about strategies for preventing and reducing side effects of cancer treatment. Therefore, having knowledge regarding the impact of hormone therapy on men's health will be important to prostate cancer survivors.     

Treatment of prostate cancer

Prostate cancer is the leading cause of cancer death among older men in western countries. However, controversy surrounds many issues related to this disease, particularly its most appropriate treatment, with a wide spectrum of opinions ranging from watchful waiting to aggressive therapy. Patients with newly diagnosed prostate cancer, as well as their doctors, will have to make difficult decisions regarding treatment of this disease. In this article we discuss the current available treatment options and some novel therapeutic approaches to tackling the patient with prostate cancer.     

Radiotherapy for locally recurrent prostate cancer

The optimal treatment of the patient at high risk for local recurrence of prostate cancer after radical prostatectomy is controversial. Similarly, there is much controversy over how to treat patients with a rising prostate-specific antigen (PSA), but without overt metastases, after radical prostatectomy. A recent randomized controlled trial of adjuvant radiotherapy versus observation following radical prostatectomy shows a significantly higher freedom from recurrence for patients receiving adjuvant radiotherapy, which may help to resolve the question of whether or not to wait for a rise in the PSA before offering treatment. For patients with biochemical recurrence after prostatectomy, part of the problem lies in the difficulty in determining whether a rise in the PSA is a sign of local recurrence or a harbinger of distant metastases. Making this distinction is critical, since patients with local disease may be cured with radiation therapy to the prostate bed, whereas those with metastatic disease will require a different treatment approach. In this article, we discuss the factors that must be taken into consideration when making treatment recommendations for these patients. In addition, approaches to the evaluation and management of patients with this difficult clinical problem are presented.     

The LITE study: Rationale and protocol for a randomized controlled trial of light therapy for cancer-related fatigue in cancer survivors

Fatigue is a common and distressing symptom that can last for months or years in up to one-third of cancer survivors. Despite its prevalence, the nature and mechanisms of cancer-related fatigue are poorly understood and the available treatments may not provide sufficient relief. Fatigue has been identified as a significant contributor to decreased quality of life, making it an important target for intervention. One approach that may be a safe and inexpensive treatment is bright light therapy.MethodsThis study is a 4-week blinded randomized controlled trial. Subjects will be men and women who meet criteria for cancer-related fatigue and have completed cancer treatment. Subjects will be randomly assigned to receive a Litebook treatment device that produces either bright white light (treatment) or dim red light (active control). The devices will be used daily for 30 min upon waking for a period of four weeks. The primary outcome, fatigue, will be measured with the Multidimensional Fatigue Symptom Inventory-SF. Secondary outcomes include mood disturbance, sleep quality, quality of life, diurnal cortisol, and inflammatory biomarkers. Fatigue assessments will be completed weekly and secondary outcomes will be assessed at pre- and post-intervention.ConclusionsThe current research will examine the effect of light exposure on cancer-related fatigue and its potential psychological, behavioral, and biological mechanisms. If successful, this research would support the use of light therapy for the management of persistent fatigue in cancer survivors, expanding existing treatment options. It may also improve upon the current understanding of the mechanisms that underlie cancer-related fatigue.     

Prostate cancer gene therapy

With the advance in genetic engineering, tumor biology and immunology, gene therapy has been recognized as a promising new treatment option for cancer including prostate cancer. Several clinical trials of prostate cancer gene therapy are currently underway, using therapeutic genes which include suicide genes, immunomodulatory genes, tumor suppressor genes and anti-oncogenes. Although the gene therapy for prostate cancer as a clinical alternative is still early stage which requires several technological breakthrough, some information obtained from clinical trial indicates full potential of prostate cancer gene therapy. Concordant progress both in the basic research and gene therapy technology will make prostate cancer gene therapy ready for wide scale of practice in the future. In this report, general concept and current progress in prostate cancer gene therapy are summarized.     

Prostate cancer gene therapy

With the advance in genetic engineering, tumor biology and immunology, gene therapy has been recognized as a promising new treatment option for cancer including prostate cancer. Several clinical trials of prostate cancer gene therapy are currently underway, using therapeutic genes which include suicide genes, immunomodulatory genes, tumor suppressor genes and anti-oncogenes. Although the gene therapy for prostate cancer as a clinical alternative is still early stage which requires several technological breakthrough, some information obtained from clinical trial indicates full potential of prostate cancer gene therapy. Concordant progress both in the basic research and gene therapy technology will make prostate cancer gene therapy ready for wide-scale of practice in the future. In this report, general concept and current progress in prostate cancer gene therapy are summarized.     

Cancer biomarkers: current issues and future directions

Cancer biomarkers and characteristics of an ideal biomarker for cancer are discussed in this review, as well as technologies for their detection. The focus of this article is on the use of biomarkers for anticancer drug development and clinical applications, including determination of prognosis as well as monitoring of response to therapy. Types of biomarkers include methylated DNA sequences, mitochondrial DNA and microRNA. Within clinical research, oncology is expected to have the largest gains from biomarkers over the next five to ten years. Development of personalized medicine for cancer is closely linked to biomarkers, which may serve as the basis for diagnosis, drug discovery and monitoring of diseases. A major challenge in development of cancer biomarkers will be the integration of proteomics with genomics and metabolomics data and their functional interpretation in conjunction with clinical data and epidemiology.     

疗效预测生物标志物在去势抵抗性前列腺癌中的研究进展

免疫检查点抑制剂(ICIs)疗法在治疗多种晚期实体瘤中取得了革命性的突破,其中包括了去势抵抗性前列腺癌(CRPC).在过去几年中,已有多种ICIs应用于CRPC,并证明可改善患者的总生存期(OS),但是由于适用人群受限以及毒副作用大,大部分药物的临床获益很少是持久的.目前可预测ICIs在CRPC疗效的生物标志物仍欠缺可...     

Use of Positron Emission Tomography to Target Prostate Cancer Gene Therapy by Oncolytic Herpes Simplex Virus

Herpes simplex virus (HSV) oncolytic gene therapy is a promising treatment modality against cancer. We have demonstrated that androgen-induced cellular changes enhance oncolytic viral replication and improve efficacy in the treatment of androgen-dependent prostate cancer cell line. Imaging of changes in 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) uptake by positron emission tomography (PET) is a sensitive method of detecting altered cellular metabolism involved in cancer therapy. We therefore hypothesized that FDG-PET can predict tumor response to oncolytic HSV therapy. In this study, androgen increased cell kill (74%) in vitro and enhanced viral yield (2.4-fold) in vivo following HSV therapy. This enhanced efficacy was predicted by high FDG accumulation in intact animals compared to low FDG uptake following orchiectomy (p = 0.002). This proof-of-concept study provides the mechanistic basis for selecting patients for targeted oncolytic viral therapy by means of a noninvasive molecular imaging method in the treatment of prostate cancer. Second author with equal contribution.     

Hormone-refractory prostate cancer: a shifting paradigm in treatment

Prostate cancer, the most common male cancer, affects one in eight American men. Risk factors for the disease include increased age, race, and family history of prostate cancer. To date, surgery, radiation, and hormonal therapy have been the mainstays of treatment. In the past, chemotherapy served only a palliative role for men with prostate cancer and failed to produce a survival advantage or any significant measurable disease response. However, for the first time, docetaxel-based regimens have demonstrated improved survival in men with hormone-refractory prostate cancer in two different, large, phase III studies. Additionally, a number of novel agents are being developed with the hope that treatment for men with hormone-refractory prostate cancer will be improved. Oncology nurses provide critical symptom management strategies as well as education to men with prostate cancer and their partners. Therefore, maintaining current state of the knowledge about best practices and treatment for prostate cancer is crucial. This, in turn, directs efforts to educate patients and family members about treatments and management of side effects.     

Novel therapeutic approaches to advanced prostate cancer

Considerable progress in the treatment of advanced prostate cancer was made in 2004 with the approval by the US Food and Drug Administration of docetaxel for the treatment of metastatic hormone-refractory prostate cancer. The survival benefit with docetaxel and prednisone, however, has been modest, on the order of 2-3 months compared with mitoxantrone and prednisone. While docetaxel-based therapy has demonstrated improvement in symptomatic and quality-of-life endpoints, certainly there is a pressing need for improvement in outcomes. A number of novel agents are in basic and clinical development for advanced prostate cancer, some of which are specific to mechanisms that may be important in the development and spread of prostate cancer. Novel approaches including immunotherapy, antiangiogenic compounds, and cell growth and survival pathway inhibitors, as well as targeted cytotoxic compounds, are among the broad categories that will be discussed in this review. Clinical advances in meaningful endpoints such as survival and quality of life are eagerly awaited in large-scale trials of active and rationally designed agents.     

HER3 mRNA as a predictive biomarker in anticancer therapy

Importance of the field: Heterodimerization of human EGF receptor (HER) 2 and HER3, a co-receptor of HER2, plays an important and dominant role in the functionality and transformation of HER-mediated pathways. Understanding the role of HER3 in oncogenesis as well as its place as a target for anticancer therapy is an ongoing area of research. Determination of biomarkers for clinical benefit from agents targeting HER3 is an essential component of translating basic science into real-world effective anticancer therapies, with the aim of ensuring the patients most likely to benefit from such treatments can be identified.

Areas covered in this review: This review focuses on the targeting of HER2 and HER3 by monoclonal antibodies and the potential for HER3 mRNA levels to predict treatment outcome in ovarian cancer.

What the reader will gain: An understanding of the value of biomarkers for clinical benefit to anticancer therapy and the current status of HER3 mRNA as a biomarker for clinical benefit of the HER2–HER3 dimerization inhibitor pertuzumab.

Take home message: HER3 mRNA levels may be a biomarker for active ligand-induced HER2–HER3 signaling, with low HER3 mRNA levels correlated with clinical benefit from the HER2–HER3 dimerization inhibitor pertuzumab.     

Prostate cancer: value of magnetic resonance spectroscopy 3D chemical shift imaging

The results of recent studies of magnetic resonance imaging (MRI) combined with three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI) demonstrate that the MRI/3D-MRSI exam is a unique method by which to noninvasively study the cellular metabolism and anatomy of the prostate. 3D-MRSI is emerging as the most specificity tool for non-invasive evaluation of the prostate cancer. The results of current MRI/3D-MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy, as well as the extent of the time course of metabolic changes after therapy, may improve our understanding of cancer aggressiveness. Assessment of cancer spread outside the prostate can be significantly improved by combining MRI findings with estimates of metabolic abnormalities provided by 3D-MRSI. Clinically, combined MRI/3D-MRSI has already demonstrated a potential for improved diagnosis, staging, and treatment planning for patients with prostate cancer. This article reviewed the value of 3D-MRS imaging for the diagnosis, localization, staging, aggressiveness, and treatment planning of prostate cancer.