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Pancreas Mar 2017Pancreatic adenocarcinoma has a very poor prognosis. Complete surgical resection remains the only current curative treatment. Locally advanced pancreatic cancers are... (Review)
Review
Pancreatic adenocarcinoma has a very poor prognosis. Complete surgical resection remains the only current curative treatment. Locally advanced pancreatic cancers are considered as unresectable because of involvement of celiac and/or mesenteric vessels. Irreversible electroporation has recently been introduced to induce permanent cell death by apoptosis. Irreversible electroporation is a nonthermal cell-destruction technique that was claimed to allow destruction of cancerous cells with less damage to surrounding supporting connective tissues with collagenic structure (such as nearby blood vessels, biliary ducts, and nerves) than other types of treatment. Applications on pancreatic adenocarcinoma seem promising, and this article is an up-to-date review of the first results.
Topics: Ablation Techniques; Adenocarcinoma; Apoptosis; Electroporation; Humans; Pancreatic Neoplasms; Prognosis; Reproducibility of Results
PubMed: 28187107
DOI: 10.1097/MPA.0000000000000793 -
Journal For Immunotherapy of Cancer Apr 2022Recent advances in understanding the roles of immune checkpoints in allowing tumors to circumvent the immune system have led to successful therapeutic strategies that... (Review)
Review
Recent advances in understanding the roles of immune checkpoints in allowing tumors to circumvent the immune system have led to successful therapeutic strategies that have fundamentally changed oncology practice. Thus far, immunotherapies against only two checkpoint targets have been approved, CTLA-4 and PD-L1/PD-1. Antibody blockade of these targets enhances the function of antitumor T cells at least in part by relieving inhibition of the T cell costimulatory receptor CD28. These successes have stimulated considerable interest in identifying other pathways that may bte targeted alone or together with existing immunotherapies. One such immune checkpoint axis is comprised of members of the PVR/nectin family that includes the inhibitory receptor T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains (TIGIT). Interestingly, TIGIT acts to regulate the activity of a second costimulatory receptor CD226 that works in parallel to CD28. There are currently over two dozen TIGIT-directed blocking antibodies in various phases of clinical development, testament to the promise of modulating this pathway to enhance antitumor immune responses. In this review, we discuss the role of TIGIT as a checkpoint inhibitor, its interplay with the activating counter-receptor CD226, and its status as the next advance in cancer immunotherapy.
Topics: Antigens, Differentiation, T-Lymphocyte; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Receptors, Immunologic; Receptors, Virus; T-Lymphocytes
PubMed: 35379739
DOI: 10.1136/jitc-2022-004711 -
The Journal of Pathology Apr 2020Lynch syndrome (LS) is characterised by predisposition to colorectal, endometrial, and other cancers and is caused by inherited pathogenic variants affecting the DNA... (Review)
Review
Lynch syndrome (LS) is characterised by predisposition to colorectal, endometrial, and other cancers and is caused by inherited pathogenic variants affecting the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. It is probably the most common predisposition to cancer, having an estimated prevalence of between 1/100 and 1/180. Resources such as the International Society for Gastrointestinal Hereditary Cancer's MMR gene variant database, the Prospective Lynch Syndrome Database (PLSD), and the Colon Cancer Family Register (CCFR), as well as pathological and immunological studies, are enabling advances in the understanding of LS. These include defined criteria by which to interpret gene variants, the function of MMR in the normal control of apoptosis, definition of the risks of the various cancers, and the mechanisms and pathways by which the colorectal and endometrial tumours develop, including the critical role of the immune system. Colorectal cancers in LS can develop along three pathways, including flat intramucosal lesions, which depend on the underlying affected MMR gene. This gives insights into the limitations of colonoscopic surveillance and highlights the need for other forms of anti-cancer prophylaxis in LS. Finally, it shows that the processes of autoimmunisation and immunoediting fundamentally constrain the development of tumours in LS and explain the efficacy of immune checkpoint blockade therapy in MMR-deficient tumours. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Topics: Colorectal Neoplasms, Hereditary Nonpolyposis; DNA Mismatch Repair; DNA-Binding Proteins; Endometrial Neoplasms; Female; Genetic Predisposition to Disease; Humans; Pathology, Molecular
PubMed: 32141610
DOI: 10.1002/path.5422 -
Annual Review of Medicine Jan 2017Lung cancer is the leading cause of cancer death in the United States and many other parts of the world. Non-small cell lung cancer (NSCLC) comprises 85-90% of lung... (Review)
Review
Lung cancer is the leading cause of cancer death in the United States and many other parts of the world. Non-small cell lung cancer (NSCLC) comprises 85-90% of lung cancers. Historically, the expected survival of patients with advanced disease has been estimated in months. In recent years, however, lung cancer has come to be seen as a treatable disease with multiple therapeutic options. Enormous advances in the understanding of its pathways and mechanisms have enabled personalized therapy in NSCLC. The evolving approach to therapy focuses on genomic profiling of the tumors to find molecular targets and develop specific agents for individualized therapy. In addition, maintenance therapy has emerged as a valid approach, and the choice of chemotherapy now varies by histology. Most recently, immunotherapy with checkpoint inhibitors has shown promising results, with impressive durations of response and a tolerable toxicity profile. Together, these discoveries have improved overall survival substantially in patient populations that have access to these advancements. We review the clinical data surrounding these impressive improvements.
Topics: Anaplastic Lymphoma Kinase; Angiogenesis Inhibitors; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Genes, erbB-1; Humans; Lung Neoplasms; Maintenance Chemotherapy; Molecular Targeted Therapy; Mutation; Platinum Compounds; Receptor Protein-Tyrosine Kinases
PubMed: 27618751
DOI: 10.1146/annurev-med-042915-102442 -
Nature Reviews. Clinical Oncology Mar 2015Locally advanced breast cancer (LABC) constitutes a heterogeneous entity that includes advanced-stage primary tumours, cancers with extensive nodal involvement and... (Review)
Review
Locally advanced breast cancer (LABC) constitutes a heterogeneous entity that includes advanced-stage primary tumours, cancers with extensive nodal involvement and inflammatory breast carcinomas. Although the definition of LABC can be broadened to include some large operable breast tumours, we use this term to strictly refer to inoperable cancers that are included in the above-mentioned categories. The prognosis of such tumours is often unfavourable; despite aggressive treatment, many patients eventually develop distant metastases and die from the disease. Advances in systemic therapy, including radiation treatment, surgical techniques and the development of new targeted agents have significantly improved clinical outcomes for patients with this disease. Notwithstanding these advances, LABC remains an important clinical problem, particularly in developing countries and those without widely adapted breast cancer awareness programmes. The optimal management of LABC requires a multidisciplinary approach, a well-coordinated treatment schedule and close cooperation between medical, surgical and radiation oncologists. In this Review, we discuss the current state of the art and possible future treatment strategies for patients with LABC.
Topics: Breast Neoplasms; Combined Modality Therapy; Disease Management; Female; Humans; Neoplasm Staging; Prognosis; Risk Factors
PubMed: 25668732
DOI: 10.1038/nrclinonc.2015.13 -
Modern Pathology : An Official Journal... Jul 2023Our understanding of the biology and management of human disease has undergone a remarkable evolution in recent decades. Improved understanding of the roles of complex... (Review)
Review
Our understanding of the biology and management of human disease has undergone a remarkable evolution in recent decades. Improved understanding of the roles of complex immune populations in the tumor microenvironment has advanced our knowledge of antitumor immunity, and immunotherapy has radically improved outcomes for many advanced cancers. Digital pathology has unlocked new possibilities for the assessment and discovery of the tumor microenvironment, such as quantitative and spatial image analysis. Despite these advances, tissue-based evaluations for diagnosis and prognosis continue to rely on traditional practices, such as hematoxylin and eosin staining, supplemented by the assessment of single biomarkers largely using chromogenic immunohistochemistry (IHC). Such approaches are poorly suited to complex quantitative analyses and the simultaneous evaluation of multiple biomarkers. Thus, multiplex staining techniques have significant potential to improve diagnostic practice and immuno-oncology research. The different approaches to achieve multiplexed IHC and immunofluorescence are described in this study. Alternatives to multiplex immunofluorescence/IHC include epitope-based tissue mass spectrometry and digital spatial profiling (DSP), which require specialized platforms not available to most clinical laboratories. Virtual multiplexing, which involves digitally coregistering singleplex IHC stains performed on serial sections, is another alternative to multiplex staining. Regardless of the approach, analysis of multiplexed stains sequentially or simultaneously will benefit from standardized protocols and digital pathology workflows. Although this is a complex and rapidly advancing field, multiplex staining is now technically feasible for most clinical laboratories and may soon be leveraged for routine diagnostic use. This review provides an update on the current state of the art for tissue multiplexing, including the capabilities and limitations of different techniques, with an emphasis on potential relevance to clinical diagnostic practice.
Topics: Humans; Immunohistochemistry; Pathologists; Fluorescent Antibody Technique; Neoplasms; Biomarkers; Coloring Agents; Biomarkers, Tumor; Tumor Microenvironment
PubMed: 37105494
DOI: 10.1016/j.modpat.2023.100197 -
Nature Reviews. Cancer Oct 2021Whole-genome sequencing has brought the cancer genomics community into new territory. Thanks to the sheer power provided by the thousands of mutations present in each... (Review)
Review
Whole-genome sequencing has brought the cancer genomics community into new territory. Thanks to the sheer power provided by the thousands of mutations present in each patient's cancer, we have been able to discern generic patterns of mutations, termed 'mutational signatures', that arise during tumorigenesis. These mutational signatures provide new insights into the causes of individual cancers, revealing both endogenous and exogenous factors that have influenced cancer development. This Review brings readers up to date in a field that is expanding in computational, experimental and clinical directions. We focus on recent conceptual advances, underscoring some of the caveats associated with using the mutational signature frameworks and highlighting the latest experimental insights. We conclude by bringing attention to areas that are likely to see advancements in clinical applications.
Topics: Carcinogenesis; DNA Mutational Analysis; Genomics; Humans; Mutation; Neoplasms
PubMed: 34316057
DOI: 10.1038/s41568-021-00377-7 -
Nature Reviews. Cancer Feb 2022Advances in quantitative biomarker development have accelerated new forms of data-driven insights for patients with cancer. However, most approaches are limited to a... (Review)
Review
Advances in quantitative biomarker development have accelerated new forms of data-driven insights for patients with cancer. However, most approaches are limited to a single mode of data, leaving integrated approaches across modalities relatively underdeveloped. Multimodal integration of advanced molecular diagnostics, radiological and histological imaging, and codified clinical data presents opportunities to advance precision oncology beyond genomics and standard molecular techniques. However, most medical datasets are still too sparse to be useful for the training of modern machine learning techniques, and significant challenges remain before this is remedied. Combined efforts of data engineering, computational methods for analysis of heterogeneous data and instantiation of synergistic data models in biomedical research are required for success. In this Perspective, we offer our opinions on synthesizing complementary modalities of data with emerging multimodal artificial intelligence methods. Advancing along this direction will result in a reimagined class of multimodal biomarkers to propel the field of precision oncology in the coming decade.
Topics: Artificial Intelligence; Genomics; Humans; Medical Oncology; Neoplasms; Precision Medicine
PubMed: 34663944
DOI: 10.1038/s41568-021-00408-3 -
The Oncologist Feb 2016Adenocarcinoma of the pancreas remains a highly lethal disease, with less than 5% survival at 5 years. Borderline resectable pancreatic cancer (BRPC) and locally... (Review)
Review
UNLABELLED
Adenocarcinoma of the pancreas remains a highly lethal disease, with less than 5% survival at 5 years. Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) account for approximately 30% of newly diagnosed cases of PC. The objective of BRPC therapy is to downstage the tumor to allow resection; the objective of LAPC therapy is to control disease and improve survival. There is no consensus on the definitions of BRPC and LAPC, which leads to major limitations in designing clinical trials and evaluating their results. A multimodality approach is always needed to ensure proper utilization and timing of chemotherapy, radiation, and surgery in the management of this disease. Combination chemotherapy regimens (5-fluorouracil, leucovorin, irinotecan, oxaliplatin, and gemcitabine [FOLFIRINOX] and gemcitabine/nab-paclitaxel) have improved overall survival in metastatic disease. The role of combination chemotherapy regimens in BRPC and LAPC is an area of active investigation. There is no consensus on the dose, modality, and role of radiation therapy in the treatment of BRPC and LAPC. This article reviews the literature and highlights the areas of controversy regarding management of BRPC and LAPC.
IMPLICATIONS FOR PRACTICE
Pancreatic cancer is one of the worst cancers with regard to survival, even at early stages of the disease. This review evaluates all the evidence for the stages in which the cancer is not primarily resectable with surgery, known as borderline resectable or locally advanced unresectable. Recently, advancements in radiation techniques and use of better combination chemotherapies have improved survival and tolerance. There is no consensus on description of stages or treatment sequences (chemotherapy, chemoradiation, radiation), nor on the best chemotherapy regimen. The evidence behind the treatment paradigm for these stages of pancreatic cancer is summarized.
Topics: Adenocarcinoma; Combined Modality Therapy; Humans; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Staging; Pancreatic Neoplasms
PubMed: 26834159
DOI: 10.1634/theoncologist.2015-0316 -
Journal of Mammary Gland Biology and... Jul 2003Advances in comprehensive genomic and proteomic technologies are providing researchers with an unprecedented opportunity for high-throughput molecular analysis of human... (Review)
Review
Advances in comprehensive genomic and proteomic technologies are providing researchers with an unprecedented opportunity for high-throughput molecular analysis of human breast cancer. Adaptation of these technologies to laser capture microdissection (LCM) is poised to exert dramatic change on the pace of breast cancer research. Although technical limitations have impeded the coupling of these high-throughput technologies to LCM, recent advances have allowed for the successful application of this cellular-based approach to breast cancer, and the results of such studies have provided researchers with unique insight into the disease. This approach holds great potential for rapid advancement in our understanding of breast cancer, and it is hoped that such advancements will lead to novel predictive and therapeutic strategies for women with the disease. This review outlines the current status of the adaptation of advanced molecular technologies to LCM and highlights recent studies in which this approach has been applied to human breast cancer.
Topics: Breast Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Lasers; Microdissection; Oligonucleotide Array Sequence Analysis; Proteomics
PubMed: 14973377
DOI: 10.1023/b:jomg.0000010033.49464.0c