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Molecular Cancer Oct 2023Despite centuries since the discovery and study of cancer, cancer is still a lethal and intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have... (Review)
Review
Despite centuries since the discovery and study of cancer, cancer is still a lethal and intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as a pivotal component of the tumor microenvironment. The versatility and sophisticated mechanisms of CAFs in facilitating cancer progression have been elucidated extensively, including promoting cancer angiogenesis and metastasis, inducing drug resistance, reshaping the extracellular matrix, and developing an immunosuppressive microenvironment. Owing to their robust tumor-promoting function, CAFs are considered a promising target for oncotherapy. However, CAFs are a highly heterogeneous group of cells. Some subpopulations exert an inhibitory role in tumor growth, which implies that CAF-targeting approaches must be more precise and individualized. This review comprehensively summarize the origin, phenotypical, and functional heterogeneity of CAFs. More importantly, we underscore advances in strategies and clinical trials to target CAF in various cancers, and we also summarize progressions of CAF in cancer immunotherapy.
Topics: Humans; Cancer-Associated Fibroblasts; Neoplasms; Disease Progression; Immunotherapy; Tumor Microenvironment; Fibroblasts
PubMed: 37784082
DOI: 10.1186/s12943-023-01860-5 -
Cellular and Molecular Life Sciences :... Jul 2023Pancreatic cancer is typically detected at an advanced stage, and is refractory to most forms of treatment, contributing to poor survival outcomes. The incidence of... (Review)
Review
Pancreatic cancer is typically detected at an advanced stage, and is refractory to most forms of treatment, contributing to poor survival outcomes. The incidence of pancreatic cancer is gradually increasing, linked to an aging population and increasing rates of obesity and pancreatitis, which are risk factors for this cancer. Sources of risk include adipokine signaling from fat cells throughout the body, elevated levels of intrapancreatic intrapancreatic adipocytes (IPAs), inflammatory signals arising from pancreas-infiltrating immune cells and a fibrotic environment induced by recurring cycles of pancreatic obstruction and acinar cell lysis. Once cancers become established, reorganization of pancreatic tissue typically excludes IPAs from the tumor microenvironment, which instead consists of cancer cells embedded in a specialized microenvironment derived from cancer-associated fibroblasts (CAFs). While cancer cell interactions with CAFs and immune cells have been the topic of much investigation, mechanistic studies of the source and function of IPAs in the pre-cancerous niche are much less developed. Intriguingly, an extensive review of studies addressing the accumulation and activity of IPAs in the pancreas reveals that unexpectedly diverse group of factors cause replacement of acinar tissue with IPAs, particularly in the mouse models that are essential tools for research into pancreatic cancer. Genes implicated in regulation of IPA accumulation include KRAS, MYC, TGF-β, periostin, HNF1, and regulators of ductal ciliation and ER stress, among others. These findings emphasize the importance of studying pancreas-damaging factors in the pre-cancerous environment, and have significant implications for the interpretation of data from mouse models for pancreatic cancer.
Topics: Mice; Animals; Pancreatic Neoplasms; Pancreatitis; Pancreas; Acinar Cells; Carcinoma, Pancreatic Ductal; Tumor Microenvironment
PubMed: 37452870
DOI: 10.1007/s00018-023-04855-z -
Diagnostic Pathology Oct 2023Digital pathology (DP) is being increasingly employed in cancer diagnostics, providing additional tools for faster, higher-quality, accurate diagnosis. The practice of... (Review)
Review
Digital pathology (DP) is being increasingly employed in cancer diagnostics, providing additional tools for faster, higher-quality, accurate diagnosis. The practice of diagnostic pathology has gone through a staggering transformation wherein new tools such as digital imaging, advanced artificial intelligence (AI) algorithms, and computer-aided diagnostic techniques are being used for assisting, augmenting and empowering the computational histopathology and AI-enabled diagnostics. This is paving the way for advancement in precision medicine in cancer. Automated whole slide imaging (WSI) scanners are now rendering diagnostic quality, high-resolution images of entire glass slides and combining these images with innovative digital pathology tools is making it possible to integrate imaging into all aspects of pathology reporting including anatomical, clinical, and molecular pathology. The recent approvals of WSI scanners for primary diagnosis by the FDA as well as the approval of prostate AI algorithm has paved the way for starting to incorporate this exciting technology for use in primary diagnosis. AI tools can provide a unique platform for innovations and advances in anatomical and clinical pathology workflows. In this review, we describe the milestones and landmark trials in the use of AI in clinical pathology with emphasis on future directions.
Topics: Male; Humans; Artificial Intelligence; Diagnostic Imaging; Pathology, Clinical; Prostate; Neoplasms
PubMed: 37784122
DOI: 10.1186/s13000-023-01375-z -
International Journal of Nanomedicine 2023Pancreatic cancer is a highly malignant and incurable disease, characterized by its aggressive nature and high fatality rate. The most common type is pancreatic ductal... (Review)
Review
Pancreatic cancer is a highly malignant and incurable disease, characterized by its aggressive nature and high fatality rate. The most common type is pancreatic ductal adenocarcinoma (PDAC), which has poor prognosis and high mortality rate. Current treatments for pancreatic cancer mainly encompass surgery, chemotherapy, radiotherapy, targeted therapy, and combination regimens. However, despite efforts to improve prognosis, and the 5-year survival rate for pancreatic cancer remains very low. Therefore, it's urgent to explore novel therapeutic approaches. With the rapid development of therapeutic strategies in recent years, new ideas have been provided for treating pancreatic cancer. This review expositions the advancements in nano drug delivery system, molecular targeted drugs, and photo-thermal treatment combined with nanotechnology for pancreatic cancer. It comprehensively analyzes the prospects of combined drug delivery strategies for treating pancreatic cancer, aiming at a deeper understanding of the existing drugs and therapeutic approaches, promoting the development of new therapeutic drugs, and attempting to enhance the therapeutic effect for patients with this disease.
Topics: Humans; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Drug Delivery Systems; Nanotechnology
PubMed: 37489138
DOI: 10.2147/IJN.S413496 -
Molecular Cancer Jul 2023Breast cancer is the second leading cause of death for women worldwide. The heterogeneity of this disease presents a big challenge in its therapeutic management.... (Review)
Review
Breast cancer is the second leading cause of death for women worldwide. The heterogeneity of this disease presents a big challenge in its therapeutic management. However, recent advances in molecular biology and immunology enable to develop highly targeted therapies for many forms of breast cancer. The primary objective of targeted therapy is to inhibit a specific target/molecule that supports tumor progression. Ak strain transforming, cyclin-dependent kinases, poly (ADP-ribose) polymerase, and different growth factors have emerged as potential therapeutic targets for specific breast cancer subtypes. Many targeted drugs are currently undergoing clinical trials, and some have already received the FDA approval as monotherapy or in combination with other drugs for the treatment of different forms of breast cancer. However, the targeted drugs have yet to achieve therapeutic promise against triple-negative breast cancer (TNBC). In this aspect, immune therapy has come up as a promising therapeutic approach specifically for TNBC patients. Different immunotherapeutic modalities including immune-checkpoint blockade, vaccination, and adoptive cell transfer have been extensively studied in the clinical setting of breast cancer, especially in TNBC patients. The FDA has already approved some immune-checkpoint blockers in combination with chemotherapeutic drugs to treat TNBC and several trials are ongoing. This review provides an overview of clinical developments and recent advancements in targeted therapies and immunotherapies for breast cancer treatment. The successes, challenges, and prospects were critically discussed to portray their profound prospects.
Topics: Humans; Female; Triple Negative Breast Neoplasms; Immunotherapy; Combined Modality Therapy; Molecular Targeted Therapy
PubMed: 37415164
DOI: 10.1186/s12943-023-01805-y -
Cell Apr 2024Microbial communities are resident to multiple niches of the human body and are important modulators of the host immune system and responses to anticancer therapies....
Microbial communities are resident to multiple niches of the human body and are important modulators of the host immune system and responses to anticancer therapies. Recent studies have shown that complex microbial communities are present within primary tumors. To investigate the presence and relevance of the microbiome in metastases, we integrated mapping and assembly-based metagenomics, genomics, transcriptomics, and clinical data of 4,160 metastatic tumor biopsies. We identified organ-specific tropisms of microbes, enrichments of anaerobic bacteria in hypoxic tumors, associations between microbial diversity and tumor-infiltrating neutrophils, and the association of Fusobacterium with resistance to immune checkpoint blockade (ICB) in lung cancer. Furthermore, longitudinal tumor sampling revealed temporal evolution of the microbial communities and identified bacteria depleted upon ICB. Together, we generated a pan-cancer resource of the metastatic tumor microbiome that may contribute to advancing treatment strategies.
Topics: Humans; Microbiota; Neoplasm Metastasis; Neoplasms; Metagenomics; Lung Neoplasms; Immune Checkpoint Inhibitors; Neutrophils; Tumor Microenvironment; Bacteria
PubMed: 38599211
DOI: 10.1016/j.cell.2024.03.021 -
Biomolecules Jul 2023Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer... (Review)
Review
Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race. If diagnosed late and improperly treated, BCC and SCC can become locally advanced and metastasize. Malignant melanoma (MM) is less frequent but more lethal than NMSC. Given the individual and social burdens of skin cancers, performing an adequate prevention is needed. Ultraviolet (UV) ray exposure is one of the main risk factors for skin cancer. Thus, the first-choice prevention strategy is represented by photoprotection that can be both topical and systemic. The latter consists of the oral administration of molecules which protect human skin against the damaging effects of UV rays, acting through antioxidant, anti-inflammatory, or immunomodulator mechanisms. Although several compounds are commonly used for photoprotection, only a few molecules have demonstrated their effectiveness in clinical trials and have been included in international guidelines for NMSC prevention (i.e., nicotinamide and retinoids). Moreover, none of them have been demonstrated as able to prevent MM. Clinical and preclinical data regarding the most common compounds used for systemic photoprotection are reported in this review, with a focus on the main mechanisms involved in their photoprotective properties.
Topics: Humans; Skin Neoplasms; Melanoma; Carcinoma, Basal Cell; Keratosis, Actinic; Carcinoma, Squamous Cell; Syndrome; Melanoma, Cutaneous Malignant
PubMed: 37509103
DOI: 10.3390/biom13071067 -
Nature Reviews. Clinical Oncology Jul 2023Given that cancer mortality is usually a result of late diagnosis, efforts in the field of early detection are paramount to reducing cancer-related deaths and improving... (Review)
Review
Given that cancer mortality is usually a result of late diagnosis, efforts in the field of early detection are paramount to reducing cancer-related deaths and improving patient outcomes. Increasing evidence indicates that metastasis is an early event in patients with aggressive cancers, often occurring even before primary lesions are clinically detectable. Metastases are usually formed from cancer cells that spread to distant non-malignant tissues via the blood circulation, termed circulating tumour cells (CTCs). CTCs have been detected in patients with early stage cancers and, owing to their association with metastasis, might indicate the presence of aggressive disease, thus providing a possible means to expedite diagnosis and treatment initiation for such patients while avoiding overdiagnosis and overtreatment of those with slow-growing, indolent tumours. The utility of CTCs as an early diagnostic tool has been investigated, although further improvements in the efficiency of CTC detection are required. In this Perspective, we discuss the clinical significance of early haematogenous dissemination of cancer cells, the potential of CTCs to facilitate early detection of clinically relevant cancers, and the technological advances that might improve CTC capture and, thus, diagnostic performance in this setting.
Topics: Humans; Neoplastic Cells, Circulating; Neoplasms
PubMed: 37268719
DOI: 10.1038/s41571-023-00781-y -
European Urology Jul 2023Previous studies have reported on incidence and mortality patterns for individual genitourinary cancers in the USA. However, these studies addressed individual cancer...
BACKGROUND
Previous studies have reported on incidence and mortality patterns for individual genitourinary cancers in the USA. However, these studies addressed individual cancer types rather than genitourinary cancers overall.
OBJECTIVE
To comprehensively examine disparities and trends in the incidence and mortality for the four major genitourinary cancers (bladder, kidney, prostate, and testis) in the USA.
DESIGN, SETTING, AND PARTICIPANTS
We obtained incidence data from the National Cancer Institute 22-registry Surveillance, Epidemiology and End Results (SEER) database and the US Cancer Statistics database (Centers for Disease Control and Prevention) and mortality data from the National Center for Health Statistics to examine cross-sectional and temporal trends in incidence and death rates stratified by sex, race/ethnicity, and county.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Age-adjusted incidence and death rates were calculated using SEER*Stat software. Temporal trends were analyzed using Joinpoint regression for a two-sided significance level of p < 0.05.
RESULTS AND LIMITATIONS
Incidence and mortality rates for bladder and kidney cancers were two to four times higher for men than for women. Among non-Hispanic White individuals, the highest incidence rates were found in the Northeast for bladder cancer and in Appalachia for kidney cancer, whereas the highest death rates for prostate cancer were found in the West. Incidence rates increased for cancers of the kidney and testis and for advanced-stage prostate cancer in almost all racial/ethnic populations and for bladder cancer in the American Indian/Alaska Native population. Death rates increased for testicular cancer in the Hispanic population and stabilized for prostate cancer among White and Asian American/Pacific Islander men after a steady decline since the early 1990s. Study limitations include misclassification of race/ethnicity on medical records and death certificates.
CONCLUSIONS
We found persistent sociodemographic disparities and unfavorable trends in incidence or mortality for all four major genitourinary cancers. Future studies should elucidate the reasons for these patterns.
PATIENT SUMMARY
In the USA, rates of cancer cases are increasing for kidney, testis, and advanced-stage prostate cancers in the overall population, and for bladder cancer in the American Indian/Alaska Native population. Differences in the rates by sex and race/ethnicity remain.
Topics: Male; Humans; United States; Testicular Neoplasms; Incidence; Cross-Sectional Studies; Prostatic Neoplasms; Kidney Neoplasms; Urinary Bladder Neoplasms; SEER Program
PubMed: 36566154
DOI: 10.1016/j.eururo.2022.11.023