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Nature Reviews. Disease Primers Oct 2023Bladder cancer is a global health issue with sex differences in incidence and prognosis. Bladder cancer has distinct molecular subtypes with multiple pathogenic pathways... (Review)
Review
Bladder cancer is a global health issue with sex differences in incidence and prognosis. Bladder cancer has distinct molecular subtypes with multiple pathogenic pathways depending on whether the disease is non-muscle invasive or muscle invasive. The mutational burden is higher in muscle-invasive than in non-muscle-invasive disease. Commonly mutated genes include TERT, FGFR3, TP53, PIK3CA, STAG2 and genes involved in chromatin modification. Subtyping of both forms of bladder cancer is likely to change considerably with the advent of single-cell analysis methods. Early detection signifies a better disease prognosis; thus, minimally invasive diagnostic options are needed to improve patient outcomes. Urine-based tests are available for disease diagnosis and surveillance, and analysis of blood-based cell-free DNA is a promising tool for the detection of minimal residual disease and metastatic relapse. Transurethral resection is the cornerstone treatment for non-muscle-invasive bladder cancer and intravesical therapy can further improve oncological outcomes. For muscle-invasive bladder cancer, radical cystectomy with neoadjuvant chemotherapy is the standard of care with evidence supporting trimodality therapy. Immune-checkpoint inhibitors have demonstrated benefit in non-muscle-invasive, muscle-invasive and metastatic bladder cancer. Effective management requires a multidisciplinary approach that considers patient characteristics and molecular disease characteristics.
Topics: Humans; Female; Male; Treatment Outcome; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms; Urinary Bladder; Prognosis
PubMed: 37884563
DOI: 10.1038/s41572-023-00468-9 -
International Journal of Molecular... Aug 2023Urothelial carcinoma (UC), the sixth most common cancer in Western countries, includes upper tract urothelial carcinoma (UTUC) and bladder carcinoma (BC) as the most... (Review)
Review
Urothelial carcinoma (UC), the sixth most common cancer in Western countries, includes upper tract urothelial carcinoma (UTUC) and bladder carcinoma (BC) as the most common cancers among UCs (90-95%). BC is the most common cancer and can be a highly heterogeneous disease, including both non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) forms with different oncologic outcomes. Approximately 80% of new BC diagnoses are classified as NMIBC after the initial transurethral resection of the bladder tumor (TURBt). In this setting, intravesical instillation of Bacillus Calmette-Guerin (BCG) is the current standard treatment for intermediate- and high-risk patients. Unfortunately, recurrence occurs in 30% to 40% of patients despite adequate BCG treatment. Radical cystectomy (RC) is currently considered the standard treatment for NMIBC that does not respond to BCG. However, RC is a complex surgical procedure with a recognized high perioperative morbidity that is dependent on the patient, disease behaviors, and surgical factors and is associated with a significant impact on quality of life. Therefore, there is an unmet clinical need for alternative bladder-preserving treatments for patients who desire a bladder-sparing approach or are too frail for major surgery. In this review, we aim to present the strategies in BCG-unresponsive NMIBC, focusing on novel molecular therapeutic targets.
Topics: Humans; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; BCG Vaccine; Non-Muscle Invasive Bladder Neoplasms; Quality of Life; Mycobacterium bovis
PubMed: 37628785
DOI: 10.3390/ijms241612596 -
Molecular Biology Reports Sep 2023Urothelial bladder carcinoma (UC) ranks among the top ten most commonly diagnosed cancers worldwide on an annual basis. The standardized classification system for... (Review)
Review
Urothelial bladder carcinoma (UC) ranks among the top ten most commonly diagnosed cancers worldwide on an annual basis. The standardized classification system for urothelial bladder tumors is the Tumor, Node, Metastasis classification, which reflects differences between non-muscle-invasive bladder carcinoma (NMIBC) and muscle-invasive bladder carcinoma (MIBC) and it depends on the extent to which tumor has infiltrated the bladder wall and other tissues and organs. NMIBC and MIBC exhibit great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. In recent years, studies based on mRNA expression profiling revealed the existence of biologically relevant molecular subtypes of UC, which show variant molecular features that can provide more precise stratification of UC patients. Here, we present a complex classification of UC based on mRNA expression studies and molecular subtypes of NMIBC and MIBC in detail with regard to different mRNA expression profiles, mutational signatures, and infiltration by non-tumor cells. The possible impact of molecular subtyping on treatment decisions and patients' outcomes is outlined, too.
Topics: Humans; Urinary Bladder; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Mutation; Neoplasm Invasiveness
PubMed: 37525073
DOI: 10.1007/s11033-023-08689-7 -
Radiology and Oncology Mar 2024Sarcopenic obesity is a relatively new term. It is a clinical condition characterized by sarcopenia (loss of muscle mass and function) and obesity (increase in fat mass)... (Review)
Review
BACKGROUND
Sarcopenic obesity is a relatively new term. It is a clinical condition characterized by sarcopenia (loss of muscle mass and function) and obesity (increase in fat mass) that mainly affects older adults. As the incidence of sarcopenia and obesity increases worldwide, sarcopenic obesity is becoming a greater problem also in cancer patients. In fact, sarcopenic obesity is associated with poorer treatment outcomes, longer hospital stays, physical disability, and shorter survival in several cancers. Oxidative stress, lipotoxicity, and systemic inflammation, as well as altered expression of skeletal muscle anti-inflammatory myokines in sarcopenic obesity, are also associated with carcinogenesis.
CONCLUSIONS
Reported prevalence of sarcopenic obesity in cancer varies because of heterogeneity in definitions and variability in diagnostic criteria used to estimate the prevalence of sarcopenia and obesity. Therefore, the aim of this review is to describe the definitions, prevalence, and diagnostic criteria as well as the mechanisms that cancer has in common with sarcopenic obesity.
Topics: Humans; Aged; Sarcopenia; Obesity; Neoplasms; Inflammation; Treatment Outcome
PubMed: 38378031
DOI: 10.2478/raon-2024-0011 -
Cancer Cell May 2024With limited treatment options, cachexia remains a major challenge for patients with cancer. Characterizing the interplay between tumor cells and the immune...
With limited treatment options, cachexia remains a major challenge for patients with cancer. Characterizing the interplay between tumor cells and the immune microenvironment may help identify potential therapeutic targets for cancer cachexia. Herein, we investigate the critical role of macrophages in potentiating pancreatic cancer induced muscle wasting via promoting TWEAK (TNF-like weak inducer of apoptosis) secretion from the tumor. Specifically, depletion of macrophages reverses muscle degradation induced by tumor cells. Macrophages induce non-autonomous secretion of TWEAK through CCL5/TRAF6/NF-κB pathway. TWEAK promotes muscle atrophy by activating MuRF1 initiated muscle remodeling. Notably, tumor cells recruit and reprogram macrophages via the CCL2/CCR2 axis and disrupting the interplay between macrophages and tumor cells attenuates muscle wasting. Collectively, this study identifies a feedforward loop between pancreatic cancer cells and macrophages, underlying the non-autonomous activation of TWEAK secretion from tumor cells thereby providing promising therapeutic targets for pancreatic cancer cachexia.
Topics: Cachexia; Pancreatic Neoplasms; Cytokine TWEAK; Animals; Humans; Macrophages; Mice; NF-kappa B; Cell Line, Tumor; Tumor Microenvironment; Muscular Atrophy; Chemokine CCL5; Signal Transduction; TNF Receptor-Associated Factor 6; Tumor Necrosis Factors; Receptors, CCR2; Chemokine CCL2; Mice, Inbred C57BL
PubMed: 38608702
DOI: 10.1016/j.ccell.2024.03.009 -
Cells Jan 2024Cachexia is a condition characterized by substantial loss of body weight resulting from the depletion of skeletal muscle and adipose tissue. A considerable fraction of... (Review)
Review
Cachexia is a condition characterized by substantial loss of body weight resulting from the depletion of skeletal muscle and adipose tissue. A considerable fraction of patients with advanced cancer, particularly those who have been diagnosed with pancreatic or gastric cancer, lung cancer, prostate cancer, colon cancer, breast cancer, or leukemias, are impacted by this condition. This syndrome manifests at all stages of cancer and is associated with an unfavorable prognosis. It heightens the susceptibility to surgical complications, chemotherapy toxicity, functional impairments, breathing difficulties, and fatigue. The early detection of patients with cancer cachexia has the potential to enhance both their quality of life and overall survival rates. Regarding this matter, blood biomarkers, although helpful, possess certain limitations and do not exhibit universal application. Additionally, the available treatment options for cachexia are currently limited, and there is a lack of comprehensive understanding of the underlying molecular pathways associated with this condition. Thus, this review aims to provide an overview of molecular mechanisms associated with cachexia and potential therapeutic targets for the development of effective treatments for this devastating condition.
Topics: Male; Humans; Cachexia; Muscular Atrophy; Quality of Life; Muscle, Skeletal; Breast Neoplasms
PubMed: 38334644
DOI: 10.3390/cells13030252 -
Trends in Endocrinology and Metabolism:... Nov 2023Interleukin (IL)-6 elicits both anticancer and procancer effects depending on the context, which we have termed the 'exercise IL-6 enigma'. IL-6 is released from... (Review)
Review
Interleukin (IL)-6 elicits both anticancer and procancer effects depending on the context, which we have termed the 'exercise IL-6 enigma'. IL-6 is released from skeletal muscles during exercise to regulate short-term energy availability. Exercise-induced IL-6 provokes biological effects that may protect against cancer by improving insulin sensitivity, stimulating the production of anti-inflammatory cytokines, mobilising immune cells, and reducing DNA damage in early malignant cells. By contrast, IL-6 continuously produced by leukocytes in inflammatory sites drives tumorigenesis by promoting chronic inflammation and activating tumour-promoting signalling pathways. How can a molecule have such opposing effects on cancer? Here, we review the roles of IL-6 in chronic inflammation, tumorigenesis, and exercise-associated cancer prevention and define the factors that underpin the exercise IL-6 enigma.
Topics: Humans; Carcinogenesis; Cytokines; Exercise; Inflammation; Interleukin-6; Muscle, Skeletal; Neoplasms
PubMed: 37633799
DOI: 10.1016/j.tem.2023.08.001