Project description:Gastric cancer (GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities. Identification of biomarkers in a basis of clinical information and comprehensive genome analysis could improve diagnosis, prognosis, prediction of recurrence and treatment response. This review summarized the current status and approaches in GC biomarker, which could be potentially used for early diagnosis, accurate prediction of therapeutic approaches and discussed the future perspective based on the molecular classification and profiling.
Project description:In accordance with the spectrum theory of metastatic disease, an oligometastatic clinical state has been proposed as an intermediary step along the natural history of cancer with few (typically 1-3) metastatic lesions identifiable on imaging that may be amenable to metastasis-directed therapy. Effective therapy of oligometastatic disease is anticipated to impact cancer evolution by delaying progression and improving patient outcome at a minimal or acceptable cost of toxicity. There has been increasing recognition of oligometastatic disease in prostate cancer with the advent of new-generation imaging agents, most notably the recently approved PET radiotracers based on targeting prostate-specific membrane antigen. Early clinical trials with metastasis-directed therapy of oligometastases have provided evidence for delaying the employment of systematic therapy and improving outcome in selected patients. Despite these encouraging results, much needs to be investigated and learned about the underlying biology of the oligometastatic state along the evolutionary clinical course of prostate cancer, the identification of relevant imaging and nonimaging predictive and prognostic biomarkers, and the development of treatment strategies to optimize short-term and long-term patient outcome. We provide a review of the current status and the lingering challenges of this rapidly evolving clinical space in prostate cancer.
Project description:Prostate cancer (PCa) is the most common cancer in men, and the second leading cause of cancer related death in men in Western countries. The standard therapy for metastatic PCa is androgen suppression therapy (AST). Men undergoing AST eventually develop metastatic castration-resistant prostate cancer (mCRPC), of which there are limited treatment options available. Immunotherapy has presented substantial benefits for many types of cancer, but only a marginal benefit for mCRPC, at least in part, due to the immunosuppressive tumor microenvironment (TME). Current clinical trials are investigating monotherapies or combination therapies involving adoptive cellular therapy, viral, DNA vaccines, oncolytic viruses, and immune checkpoint inhibitors (ICI). Immunotherapies are also being combined with chemotherapy, radiation, and AST. Additionally, preclinical investigations show promise with the recent description of alternative ways to circumvent the immunosuppressive nature of the prostate tumor microenvironment, including harnessing the immune stimulatory NKG2D pathway, inhibiting myeloid derived suppressor cells, and utilizing immunomodulatory oncolytic viruses. Herein we provide an overview of recent preclinical and clinical developments in cancer immunotherapies and discuss the perspectives for future immunotherapies in PCa.
Project description:Metastatic castrate resistant prostate cancer (PCa) remains an incurable entity. In the era of immunotherapy, the complex PCa microenvironment poses a unique challenge to the successful application of this class of agents. However, in the last decade, a tremendous effort has been made to explore this field of therapeutics. In this review, the physiology of the cancer immunity cycle is highlighted in the context of the prostate tumor microenvironment, and the current evidence for use of various classes of immunotherapy agents including vaccines (dendritic cell based, viral vector based and DNA/mRNA based), immune checkpoint inhibitors, Chimeric antigen receptor T cell therapy, antibody-mediated radioimmunotherapy, antibody drug conjugates, and bispecific antibodies, is consolidated. Finally, the future directions for combinatorial approaches to combat PCa are discussed.
Project description:ObjectiveLocalized prostate cancer can be treated with several radiotherapeutic approaches. Proton therapy (PT) can precisely target tumors, thus sparing normal tissues and reducing side-effects without sacrificing cancer control. However, PT is a costly treatment compared with conventional photon radiotherapy, which may undermine its overall efficacy. In this review, we summarize current data on the dosimetric rationale, clinical benefits, and cost of PT for prostate cancer.MethodsAn extensive literature review of PT for prostate cancer was performed with emphasis on studies investigating dosimetric advantage, clinical outcomes, cost-effective strategies, and novel technology trends.ResultsPT is safe, and its efficacy is comparable to that of standard photon-based therapy or brachytherapy. Data on gastrointestinal, genitourinary, and sexual function toxicity profiles are conflicting; however, PT is associated with a low risk of second cancer and has no effects on testosterone levels. Regarding cost-effectiveness, PT is suboptimal, although evolving trends in radiation delivery and construction of PT centers may help reduce the cost.ConclusionPT has several advantages over conventional photon radiotherapy, and novel approaches may increase its efficacy and safety. Large prospective randomized trials comparing photon therapy with proton-based treatments are ongoing and may provide data on the differences in efficacy, toxicity profile, and quality of life between proton- and photon-based treatments for prostate cancer in the modern era.Advances in knowledgePT provides excellent physical advantages and has a superior dose profile compared with X-ray radiotherapy. Further evidence from clinical trials and research studies will clarify the role of PT in the treatment of prostate cancer, and facilitate the implementation of PT in a more accessible, affordable, efficient, and safe way.
Project description:The advent of immunotherapy has revolutionized cancer treatment. Unfortunately, this has not been the case for metastatic castration-resistant prostate cancer (mCRPC), likely due to the heterogeneous and immune-suppressive microenvironment present in prostate cancer. The identification of molecular biomarkers that could predict response to immunotherapy represents one of the current challenges in this clinical scenario. The management of advanced castration-resistant prostate cancer is rapidly evolving and immunotherapy treatments, mostly consisting of immune checkpoint inhibitors combinations, BiTE® (bispecific T-cell engager) immune therapies, and chimeric antigen receptors (CAR) are in development with promising results. This review analyses the current evidence of immunotherapy treatments for mCRPC, evaluating past failures and promising approaches and discussing the directions for future research.
Project description:Angiogenesis has been well recognized as a fundamental part of a multistep process in the evolution of cancer progression, invasion, and metastasis. Strategies for inhibiting angiogenesis have been one of the most robust fields of cancer investigation, focusing on the vascular endothelial growth factor (VEGF) family and its receptors. There are numerous regulatory drug approvals to date for the use of these agents in treating a variety of solid tumors. While therapeutic efficacy has been established, challenges remain with regards to overcoming resistance and assessing response to antiangiogenic therapies. Prostate cancer is the most common noncutaneous malignancy among American men and angiogenesis plays a role in disease progression. The use of antiangiogenesis agents in prostate cancer has been promising and is hereby explored.
Project description:With increasing treatment options available, the management of locally advanced and metastatic prostate cancer (PCa) is growing more complex, nuanced, and individualized. Strategies for combining surgery, radiation, chemotherapy, and androgen deprivation therapy (ADT) continue to evolve, as do ADT and immunotherapy options. Additionally, multiple adjunctive agents for metastatic PCa have been recently approved or are pending approval. As the number of locally advanced and metastatic prostate cancers being diagnosed rises, so does the need to consider patients' clinical situations and personal preferences. This review discusses current and potential future approaches to managing locally advanced and metastatic PCa.
Project description:Prostate Cancer (PCa) is the second most common cancer in men. Population screening using prostate specific antigen (PSA) blood test and digital rectal exam (DRE) is recommended by the NCCN, EAU and other prominent clinical guidelines. While MRI is the recommended initial test in men at risk for PCa, micro-Ultrasound (MicroUS) is a novel high resolution ultrasound technology that has shown promise in PCa detection. This article provides a narrative review of the studies to date which have been conducted to evaluate the functionality and efficacy of MicroUS within the patient care pathway for prostate cancer. A total of 13 relevant publications comparing detection of csPCa between MicroUS and mpMRI were selected. An amount of 4 publications referring to use of MicroUS for other indications were found. Each publication was evaluated for risk of bias and applicability using the Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool. The studies reviewed conclude that MicroUS detection rates for clinically significant prostate cancer diagnosis are comparable to the detection rates of mpMRI guided biopsy procedures. While the existing literature indicates that MicroUS should replace conventional TRUS for prostate imaging and biopsy, it is not yet clear whether MicroUS should be used on its own or in conjunction with mpMRI for augmenting prostate cancer detection. The ongoing OPTIMUM trial will provide evidence on how best to utilize this new technology. Early data also suggest this flexible new imaging modality has a place in local staging and active surveillance of prostate cancer as well as in bladder cancer staging.
Project description:The current standard of care for patients with metastatic prostate cancer is systemic androgen deprivation therapy, and addressing the primary tumor has been reserved for patients with localized disease. However, emerging data has called into question the universality of this paradigm. Recent studies have found treatment of the primary tumor in patients with metastatic disease not only can provide the patient with symptomatic relief but also may provide a survival benefit. The potential biological and clinical benefit for cytoreductive surgery has been also been suggested in several translational models. Thus, PubMed electronic database was queried for publications on patients with metastatic prostate cancer who underwent cytoreductive prostatectomy, using keywords including: cytoreductive prostatectomy, radical prostatectomy, metastatic prostate cancer. In this review we examine literature regarding feasibility of cytoreductive prostatectomy, oncologic outcomes, and future directions including the ongoing clinical trials in this arena. While the retrospective data is encouraging, results of these ongoing prospective trials are needed before this option is offered to patients as a reasonably safe treatment with demonstrated benefits to survival and quality of life.