-
American Family Physician Feb 2018Testicular cancer is the most common solid tumor among males 15 to 34 years of age, with an estimated 8,850 new cases and 410 deaths during 2017 in the United States.... (Review)
Review
Testicular cancer is the most common solid tumor among males 15 to 34 years of age, with an estimated 8,850 new cases and 410 deaths during 2017 in the United States. With effective treatment, the overall five-year survival rate is 97%. Risk factors for testicular cancer include undescended testis (cryptorchidism), personal or family history of testicular cancer, age, ethnicity, and infertility. The U.S. Preventive Services Task Force recommends against routine screening in asymptomatic men. Men with symptoms should receive a complete history and physical examination. Scrotal ultrasonography is the preferred initial imaging study. If a solid intratesticular mass is discovered, orchiectomy is both diagnostic and therapeutic. Staging through chest radiography, chemistry panel, liver function tests, and tumor markers guides treatment. Active surveillance, chemotherapy, retroperitoneal lymph node dissection, and radiation therapy are treatment options following orchiectomy. For patients desiring future fertility, sperm banking should be discussed early in the course of treatment. Family physicians often play a role in the care of cancer survivors and should be familiar with monitoring for recurrence and future complications, including secondary malignant neoplasms, cardiovascular risk, and infertility and subfertility.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Curriculum; Education, Medical, Continuing; Humans; Male; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Practice Guidelines as Topic; Preventive Medicine; Risk Factors; Testicular Neoplasms; United States; Young Adult
PubMed: 29671528
DOI: No ID Found -
Frontiers in Immunology 2021Cancer immunotherapy works by stimulating and strengthening the body's anti-tumor immune response to eliminate cancer cells. Over the past few decades, immunotherapy... (Review)
Review
Cancer immunotherapy works by stimulating and strengthening the body's anti-tumor immune response to eliminate cancer cells. Over the past few decades, immunotherapy has shown remarkable efficacy in the treatment of cancer, particularly the success of immune checkpoint blockade targeting CTLA-4, PD-1 and PDL1, which has led to a breakthrough in tumor immunotherapy. Tumor neoantigens, a new approach to tumor immunotherapy, include antigens produced by tumor viruses integrated into the genome and antigens produced by mutant proteins, which are abundantly expressed only in tumor cells and have strong immunogenicity and tumor heterogeneity. A growing number of studies have highlighted the relationship between neoantigens and T cells' recognition of cancer cells. Vaccines developed against neoantigens are now being used in clinical trials in various solid tumors. In this review, we summarized the latest advances in the classification of immunotherapy and the process of classification, identification and synthesis of tumor-specific neoantigens, as well as their role in current cancer immunotherapy. Finally, the application prospects and existing problems of neoantigens were discussed.
Topics: Antigens, Neoplasm; Cancer Vaccines; Humans; Immunotherapy; Neoplasms
PubMed: 33936118
DOI: 10.3389/fimmu.2021.672356 -
Frontiers in Immunology 2018NY-ESO-1 or New York esophageal squamous cell carcinoma 1 is a well-known cancer-testis antigen (CTAs) with re-expression in numerous cancer types. Its ability to elicit... (Review)
Review
NY-ESO-1 or New York esophageal squamous cell carcinoma 1 is a well-known cancer-testis antigen (CTAs) with re-expression in numerous cancer types. Its ability to elicit spontaneous humoral and cellular immune responses, together with its restricted expression pattern, have rendered it a good candidate target for cancer immunotherapy. In this review, we provide background information on NY-ESO-1 expression and function in normal and cancerous tissues. Furthermore, NY-ESO-1-specific immune responses have been observed in various cancer types; however, their utility as biomarkers are not well determined. Finally, we describe the immune-based therapeutic options targeting NY-ESO-1 that are currently in clinical trial. We will highlight the recent advancements made in NY-ESO-1 cancer vaccines, adoptive T cell therapy, and combinatorial treatment with checkpoint inhibitors and will discuss the current trends for future NY-ESO-1 based immunotherapy. Cancer treatment has been revolutionized over the last few decades with immunotherapy emerging at the forefront. Immune-based interventions have shown promising results, providing a new treatment avenue for durable clinical responses in various cancer types. The majority of successful immunotherapy studies have been reported in liquid cancers, whereas these approaches have met many challenges in solid cancers. Effective immunotherapy in solid cancers is hampered by the complex, dynamic tumor microenvironment that modulates the extent and phenotype of the antitumor immune response. Furthermore, many solid tumor-associated antigens are not private but can be found in normal somatic tissues, resulting in minor to detrimental off-target toxicities. Therefore, there is an ongoing effort to identify tumor-specific antigens to target using various immune-based modalities. CTAs are considered good candidate targets for immunotherapy as they are characterized by a restricted expression in normal somatic tissues concomitant with a re-expression in solid epithelial cancers. Moreover, several CTAs have been found to induce a spontaneous immune response, NY-ESO-1 being the most immunogenic among the family members. Hence, this review will focus on NY-ESO-1 and discuss the past and current NY-ESO-1 targeted immunotherapeutic strategies.
Topics: Animals; Antigens, Neoplasm; Biomarkers, Tumor; Cancer Vaccines; Clinical Trials as Topic; Combined Modality Therapy; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Immunity; Immunotherapy; Immunotherapy, Adoptive; Membrane Proteins; Molecular Targeted Therapy; Neoplasms; Organ Specificity; Treatment Outcome
PubMed: 29770138
DOI: 10.3389/fimmu.2018.00947 -
International Journal of Molecular... May 2021CAR-T (chimeric antigen receptor T) cells have emerged as a milestone in the treatment of patients with refractory B-cell neoplasms. However, despite having... (Review)
Review
CAR-T (chimeric antigen receptor T) cells have emerged as a milestone in the treatment of patients with refractory B-cell neoplasms. However, despite having unprecedented efficacy against hematological malignancies, the treatment is far from flawless. Its greatest drawbacks arise from a challenging and expensive production process, strict patient eligibility criteria and serious toxicity profile. One possible solution, supported by robust research, is the replacement of T lymphocytes with NK cells for CAR expression. NK cells seem to be an attractive vehicle for CAR expression as they can be derived from multiple sources and safely infused regardless of donor-patient matching, which greatly reduces the cost of the treatment. CAR-NK cells are known to be effective against hematological malignancies, and a growing number of preclinical findings indicate that they have activity against non-hematological neoplasms. Here, we present a thorough overview of the current state of knowledge regarding the use of CAR-NK cells in treating various solid tumors.
Topics: Animals; Antigens, Neoplasm; Cell Culture Techniques; Clinical Trials as Topic; Combined Modality Therapy; Disease Models, Animal; Drug Evaluation, Preclinical; Genetic Engineering; Humans; Immunotherapy, Adoptive; Killer Cells, Natural; Neoplasms; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Treatment Outcome
PubMed: 34072732
DOI: 10.3390/ijms22115899 -
Cells Jan 2021The P2X7 receptor for extracellular ATP is a well-established mediator of tumoral development and progression both in solid cancers and hematological malignancies. The... (Review)
Review
The P2X7 receptor for extracellular ATP is a well-established mediator of tumoral development and progression both in solid cancers and hematological malignancies. The human P2X7 gene is highly polymorphic, and several splice variants of the receptor have been identified in time. P2X7 single-nucleotide polymorphisms (SNPs) have been broadly analyzed by studies relating them to pathologies as different as infectious, inflammatory, nervous, and bone diseases, among which cancer is included. Moreover, in the last years, an increasing number of reports concentrated on P2X7 splice variants' different roles and their implications in pathological conditions, including oncogenesis. Here, we give an overview of established and recent literature demonstrating a role for human P2X7 gene products in oncological conditions, mainly focusing on current data emerging on P2X7 isoform B and nfP2X7. We explored the role of these and other genetic variants of P2X7 in cancer insurgence, dissemination, and progression, as well as the effect of chemotherapy on isoforms expression. The described literature strongly suggests that P2X7 variants are potential new biomarkers and therapeutical targets in oncological conditions and that their study in carcinogenesis deserves to be further pursued.
Topics: Carcinogenesis; Humans; Neoplasm Proteins; Neoplasms; Polymorphism, Single Nucleotide; Protein Isoforms; Receptors, Purinergic P2X7
PubMed: 33477845
DOI: 10.3390/cells10010189 -
Chemical Society Reviews Feb 2019Hypoxia is a state of low oxygen tension found in numerous solid tumours. It is typically associated with abnormal vasculature, which results in a reduced supply of... (Review)
Review
Hypoxia is a state of low oxygen tension found in numerous solid tumours. It is typically associated with abnormal vasculature, which results in a reduced supply of oxygen and nutrients, as well as impaired delivery of drugs. The hypoxic nature of tumours often leads to the development of localized heterogeneous environments characterized by variable oxygen concentrations, relatively low pH, and increased levels of reactive oxygen species (ROS). The hypoxic heterogeneity promotes tumour invasiveness, metastasis, angiogenesis, and an increase in multidrug-resistant proteins. These factors decrease the therapeutic efficacy of anticancer drugs and can provide a barrier to advancing drug leads beyond the early stages of preclinical development. This review highlights various hypoxia-targeted and activated design strategies for the formulation of drugs or prodrugs and their mechanism of action for tumour diagnosis and treatment.
Topics: Animals; Antineoplastic Agents; Cell Hypoxia; Drug Delivery Systems; Drug Design; Drug Liberation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms; Prodrugs; Tumor Microenvironment
PubMed: 30575832
DOI: 10.1039/c8cs00304a -
Cells Jul 2021Metastasis accounts for the highest mortality rates in solid tumor cancer patients. However, research and development have neglected this most lethal characteristic and,...
Metastasis accounts for the highest mortality rates in solid tumor cancer patients. However, research and development have neglected this most lethal characteristic and, instead, have concentrated on the hallmarks of cancer that make tumor cells highly proliferative and distinctive from nonmalignant cells. The concentration on invasion and metastasis can be one of the most meaningful advancements in cancer investigation. Importantly, metastasis-free survival (MFS) was recently approved by the Food and Drug Administration (FDA) as a novel primary endpoint in clinical trials and has been used to evaluate the prognosis of patients with nonmetastatic castration-resistant prostate cancer and soft tissue sarcoma. This new definition enables to shift the focus of research and development in cancer therapeutics toward metastasis and to change the emphasis from using tumor shrinkage as a benchmark for indicating the efficacy of treatment to using MFS as a more representative endpoint for antimetastatic drugs. This perspective outlines the possibility to use this novel endpoint in other solid cancers, and examples of large clinical trials are given in which MFS is defined as an endpoint and/or in which antimetastatic strategies are being examined. These advances now open the door for the rapid development of antimetastatic therapies, which could be used in combination with standard cytotoxic cancer therapies. With pioneer research on metastasis prevention on the rise and the underlying biomechanisms of tumor cell motility and invasion explored further than ever before, we believe an intensified focus on antimetastatic properties will shape this era of cancer translational research.
Topics: Animals; Antineoplastic Agents; Cell Movement; Clinical Trials as Topic; Endpoint Determination; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Progression-Free Survival; Research Design; Translational Research, Biomedical
PubMed: 34440616
DOI: 10.3390/cells10081845 -
Archives of Pathology & Laboratory... Jul 2020Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor generally associated with a good prognosis. Solid pseudopapillary neoplasms show peculiar... (Review)
Review
CONTEXT.—
Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor generally associated with a good prognosis. Solid pseudopapillary neoplasms show peculiar morphologic features, but sometimes the differential diagnosis with other pancreatic neoplasms (ie, pancreatic neuroendocrine tumors) can be a challenging task, especially in cytologic or biopsy specimens. In these cases immunohistochemistry is a useful tool, but the diagnostic utility of several proposed immunohistochemical markers is questionable. In recent years, despite several attempts to characterize the pathogenetic, molecular, and prognostic features of solid pseudopapillary neoplasms, they still remain unclear.
OBJECTIVE.—
To give the reader a comprehensive update on this entity.
DATA SOURCES.—
The PubMed database (US National Library of Medicine) was searched using the following string: pseudopapillary tumor [AND/OR] neoplasm [AND/OR] pancreas. All articles written in English were included. In addition, because a heterogeneous terminology has been used in the past to define solid pseudopapillary neoplasms, the reference lists of each paper selected in the PubMed database were also reviewed.
CONCLUSIONS.—
This review gives a comprehensive update on the pathologic, clinical, and molecular features of solid pseudopapillary neoplasms, particularly addressing issues and challenges related to diagnosis. In addition, we have tried to correlate the molecular alterations with the morphologic and clinical features.
Topics: Biomarkers, Tumor; Biopsy; Diagnosis, Differential; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Molecular Diagnostic Techniques; Pancreatic Neoplasms; Phenotype; Predictive Value of Tests; Prognosis
PubMed: 31958381
DOI: 10.5858/arpa.2019-0473-RA -
Frontiers in Immunology 2020HLA-G is known to modulate the immune system activity in tissues where physiological immune-tolerance is necessary (i.e., maternal-fetal interface, thymus, and cornea).... (Review)
Review
HLA-G is known to modulate the immune system activity in tissues where physiological immune-tolerance is necessary (i.e., maternal-fetal interface, thymus, and cornea). However, the frequent neo-expression of HLA-G in many cancer types has been previously and extensively described and is correlated with a bad prognosis. Despite being an MHC class I molecule, HLA-G is highly present in tumor context and shows unique characteristics of tissue restriction of a Tumor Associated Antigen (TAA), and potent immunosuppressive activity of an Immune CheckPoint (ICP). Consequently, HLA-G appears to be an excellent molecular target for immunotherapy. Although the relevance of HLA-G in cancer incidence and development has been proven in numerous tumors, its neo-expression pattern is still difficult to determine. Indeed, the estimation of HLA-G's actual expression in tumor tissue is limited, particularly concerning the presence and percentage of the new non-canonical isoforms, for which detection antibodies are scarce or inexistent. Here, we summarize the current knowledge about HLA-G neo-expression and implication in various tumor types, pointing out the need for the development of new tools to analyze in-depth the HLA-G neo-expression patterns, opening the way for the generation of new monoclonal antibodies and cell-based immunotherapies.
Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Antineoplastic Agents, Immunological; HLA-G Antigens; Humans; Immunotherapy, Adoptive; Neoplasms; Tumor Escape; Tumor Microenvironment
PubMed: 32922387
DOI: 10.3389/fimmu.2020.01685 -
Cancer Cytopathology Jul 2022The classification and management of solid pancreatic neoplasms has expanded significantly in recent years because of advances in immunohistochemical markers, molecular... (Review)
Review
The classification and management of solid pancreatic neoplasms has expanded significantly in recent years because of advances in immunohistochemical markers, molecular diagnostics, and therapeutics. Solid pancreatic masses are subdivided into 1) ill-defined, scirrhous, and stroma-rich (ductal adenocarcinoma) and 2) well circumscribed, cellular, and stroma-poor (including neuroendocrine neoplasms, acinar cell carcinoma, pancreatoblastoma, and solid-pseudopapillary neoplasm). Definitive diagnosis, particularly of stroma-poor, circumscribed tumors, requires the incorporation of radiologic and cytologic findings, along with the judicious use of (broad, but limited) immunohistochemical panels (pancytokeratin and neuroendocrine [synaptophysin], acinar [trypsin], and solid-pseudopapillary neoplasm [β-catenin] markers), along with unstained slides. Depending on the initial results, immunohistochemical panels should be expanded to include more confirmatory (acinar and neuroendocrine) markers. This ensures that adequate material is available for definitive diagnosis/subclassification and, in some cases, grading, and/or molecular studies, particularly of grade 3 neuroendocrine neoplasms and mixed-lineage tumors. The objective of this review is to expand the understanding of the cytomorphology of solid pancreatic neoplasms using an integrated, multidisciplinary approach in their diagnosis. Knowledge and understanding of recent updates in the classification of solid pancreatic neoplasms ensures that cytopathologists appropriately triage specimens, judiciously use and interpret ancillary studies, and incorporate these results in reporting.
Topics: Biomarkers, Tumor; Carcinoma, Acinar Cell; Humans; Neuroendocrine Tumors; Pancreatic Neoplasms
PubMed: 35594486
DOI: 10.1002/cncy.22597