Abstract:
:Renal cell carcinoma (RCC) is increasing in incidence and one third of newly diagnosed cases already are metastatic. The metastatic spread of solid tumors renders RCC incurable by surgical resection and consequently more difficult to treat. New molecular-targeted therapies have played a pivotal role in RCC treatment. Unfortunately, tumors frequently develop resistance to these targeted therapies by activating bypass pathways in which alternative signaling or biochemical pathways are activated in response to targeted inhibition of a signaling pathway, allowing cancer cells to continue to survive. Although the advent of immunotherapy with checkpoint inhibitors has led to significant changes in the treatment landscape for advanced RCC, many issues remain to be resolved. For these reasons, there is an urgent need to develop novel therapies and new treatment paradigms for patients with RCC. Much research has been performed thus far in identifying novel targets and treatment strategies in RCC and many of these currently are under investigation and/or in clinical trials. In this article, we discuss therapeutic options in the management of RCC with a focus on the new therapeutic approaches currently investigated in research and for use in the clinic. We divide these potential novel therapies into five groups: nonbiologics, small-molecule drugs, biologics, immunomodulatory therapies, and peptide drugs. We also present some therapeutics and treatment paradigms.
journal_name
Semin Nephroljournal_title
Seminars in nephrologyauthors
Yang DC,Chen CHdoi
10.1016/j.semnephrol.2019.12.010subject
Has Abstractpub_date
2020-01-01 00:00:00pages
86-97issue
1eissn
0270-9295issn
1558-4488pii
S0270-9295(19)30120-2journal_volume
40pub_type
杂志文章,评审abstract::Cyclooxygenase inhibitors have long been used in experimental studies as well as in clinical practice to reduce urinary protein excretion in proteinuric renal diseases. However, the mechanisms by which this treatment limits glomerular filtration of proteins are not fully elucidated. We will review the cellular and mol...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:
更新日期:1995-05-01 00:00:00
abstract::Neuroimmune interaction is an emerging concept, wherein the nervous system modulates the immune system and vice versa. This concept is gaining attention as a novel therapeutic target in various inflammatory diseases including acute kidney injury (AKI). Vagus nerve stimulation or treatment with pulsed ultrasound activa...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2018.10.008
更新日期:2019-01-01 00:00:00
abstract::As kidney function declines, chronic kidney disease (CKD) becomes an increasingly systemic disorder. Most patients with CKD eventually develop subclinical or clinical abnormalities in bone and mineral metabolism. Recent observational and basic scientific studies have led to a new emphasis on the changes in phosphorus ...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2009.01.002
更新日期:2009-03-01 00:00:00
abstract::Renal involvement is common in leptospirosis. Clinical manifestations vary from urinary sediment changes to acute renal failure. Renal failure is observed in 44% to 67% of patients. Hypokalemia frequently occurs. Severe hypotension is an important warning sign for the later development of renal and pulmonary complicat...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1053/snep.2003.50004
更新日期:2003-01-01 00:00:00
abstract::Acid-base balance is critical for normal life. Acute and chronic disturbances impact cellular energy metabolism, endocrine signaling, ion channel activity, neuronal activity, and cardiovascular functions such as cardiac contractility and vascular blood flow. Maintenance and adaptation of acid-base homeostasis are most...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2019.04.004
更新日期:2019-07-01 00:00:00
abstract::There are several published series of pregnancy in patients with nonimmunoglobulin A mesangial proliferative glomerulonephritis (most of whom have thin basement membrane nephropathy [TBMN]). The aim of the present study was to review the maternal and fetal outcomes of pregnancy in women with TBMN. The medical and obst...
journal_title:Seminars in nephrology
pub_type: 杂志文章
doi:10.1016/j.semnephrol.2005.01.011
更新日期:2005-05-01 00:00:00
abstract::Preeclampsia is a 2-stage disorder. Stage 1 is decreased placental perfusion and generates stage 2 of the disorder, the maternal syndrome characteristic of preeclampsia. How the 2 stages are linked has been a topic of intense investigation for many years. One candidate phenomenon, which includes many other suggested l...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/s0270-9295(04)00126-3
更新日期:2004-11-01 00:00:00
abstract::Stephen Hales was the first to measure blood pressure directly in the horse (1733), and the definitive studies on human nephrins by Richard Bright followed much later (1836). The relation between high blood pressure and renal disease was established by Mahomed (1872). The discovery of renin and its possible link with ...
journal_title:Seminars in nephrology
pub_type: 历史文章,杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract::Advances in information technology have changed human interactions. These changes have had considerable implications for nonmedical and medical educational practices. The use of semi-private applications such as WhatsApp (Mountain View, CA), Slack (Canada), Viber (Israel), and Google Hangouts (Mountain View, CA) has n...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2020.04.010
更新日期:2020-05-01 00:00:00
abstract::The search for an endogenous digitalis has led to the identification of the cardenolides ouabain and digoxin and the bufadienolide marinobufagenin in mammalian tissues and biological fluids. Ouabain's release from adrenal glands is under the control of epinephrine and angiotensin II; hence, its blood concentration cha...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2005.03.010
更新日期:2005-09-01 00:00:00
abstract::Worldwide, more than 250,000 individuals who have received a liver, heart, lung, or intestinal transplant are living longer. Twenty percent to 25% of these recipients experience perioperative acute renal failure, with 10% to 15% requiring renal replacement therapy. Chronic kidney disease (CKD) is also highly prevalent...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2007.03.010
更新日期:2007-07-01 00:00:00
abstract::We related 24-hour sodium and potassium excretion cross-sectionally to blood pressure and longitudinally to coronary events and deaths during follow-up in a representative sample of the Scottish population. A random sampling of men and women aged 40-59 in 1984 to 1987 produced 11,629 men and women who provided questio...
journal_title:Seminars in nephrology
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::Membranous nephropathy is a relatively common glomerular disease found to underlie both nonnephrotic and nephrotic proteinuria. In adults, about 75% of cases are primary (idiopathic) and 25% are secondary to a wide variety of causes, including neoplasia, infections, autoimmunity, and drugs. Presenting features are not...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/s0270-9295(03)00049-4
更新日期:2003-07-01 00:00:00
abstract::Care of patients with type 1 diabetes (T1D) has changed during the past 30 years. Tools to control hyperglycemia have improved and it was shown that improvement in glycemic control diminished the risk of late diabetic complications, including nephropathy. Moreover, in patients with impaired renal function, aggressive ...
journal_title:Seminars in nephrology
pub_type: 杂志文章
doi:10.1016/j.semnephrol.2012.07.002
更新日期:2012-09-01 00:00:00
abstract::Acute kidney injury (AKI) is common in the setting of shock. Hemodynamic instability is a risk factor for the development of AKI, and pathophysiological mechanisms include loss of renal perfusion pressure and impaired microcirculation. Although restoration of mean arterial pressure (MAP) may mitigate the risk of AKI t...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2019.06.006
更新日期:2019-09-01 00:00:00
abstract::The apical membrane epithelial Na(+) channel subunit (ENaC) in series with the basolateral Na(+)/K(+)-adenosine triphosphatase mediates collecting duct Na(+) reabsorption. Aldosterone induces αENaC gene transcription, which appears to be rate limiting for ENaC activity in this segment. Although this response has long ...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2013.05.010
更新日期:2013-07-01 00:00:00
abstract::Given the prohibitive costs of end-stage renal disease (ESRD) care for certain countries and the increasing incidence of ESRD worldwide, alternative methods of funding dialysis care are increasingly necessary. We describe the paradigm of the National Kidney Foundation of Singapore (NKF-S), the provider of subsidized d...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1053/snep.2001.23776
更新日期:2001-07-01 00:00:00
abstract::On completion of a Nephrology fellowship, I went back to the inner city community where I was raised to begin my practice. Filled with idealism, I believed that, by returning, I could slow the devastation that hypertension was imparting on the black community, and in doing so, prevent end-stage renal disease (ESRD). I...
journal_title:Seminars in nephrology
pub_type: 杂志文章
doi:10.1053/snep.2001.23688
更新日期:2001-07-01 00:00:00
abstract::Membranous nephropathy remains the most common cause of the nephrotic syndrome in adults. Most patients do well with long-term natural history studies reporting a 10-year renal survival of 70% to 90% but the remainder progress to end stage renal failure. This plus the associated morbidity of those with persistent high...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:
更新日期:2000-05-01 00:00:00
abstract::A review is presented of 164 nephrotic patients who were older than 60 years at the onset of their nephrotic syndrome, together with a review of more than 1,000 patients from the literature. The nephrotic syndrome in elderly patients is as common as in younger adults, but is often misdiagnosed as "heart failure" by pr...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:
更新日期:1996-07-01 00:00:00
abstract::Despite intensive research over the past three decades, the events leading to pathogenic autoantibody production and immune deposit formation in individuals with systemic lupus erythematosus continues to be debated. The controversy is fueled by the clinical observations that individual patients with lupus have variabl...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00
abstract::Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with renal failure. Patients with chronic kidney disease have significant CVD, and carry a high cardiovascular burden by the time they commence renal replacement therapy (RRT). The severity of CVD that has been observed in dialysis ...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1053/snep.2002.35964
更新日期:2002-11-01 00:00:00
abstract::Autophagy is a ubiquitous intracellular catabolic process that contributes to homeostatic maintenance and regulates the balance between health and disease. Emerging evidence from both the immunology and renal literature suggests that important relationships exist between the immune system and renal autophagy that may ...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2013.11.008
更新日期:2014-01-01 00:00:00
abstract::Peritoneal dialysis (PD) may be a feasible, safe, and complementary alternative to hemodialysis not only in the chronic setting, but also in the acute setting. It previously was widely accepted for acute kidney injury (AKI) treatment, but its practice decreased in favor of other types of extracorporeal therapies. The ...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2016.10.011
更新日期:2017-01-01 00:00:00
abstract::Small lipids such as eicosanoids exert diverse and complex functions. In addition to their role in regulating normal kidney function, these lipids also play important roles in the pathogenesis of kidney diseases. Increased glomerular cyclooxygenase (COX)1 or COX2 expression has been reported in patients with nephritis...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2007.02.008
更新日期:2007-05-01 00:00:00
abstract::Effectiveness of antihypertensive agents is assessed not only by systemic blood pressure levels, but by multiple parameters that reflect specific organ functions. Among antihypertensive agents, those which inhibit angiotensin actions show particular efficacy in ameliorating end organ damage. This efficacy likely refle...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:
更新日期:1996-11-01 00:00:00
abstract::Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by bone abnormalities, vascular calcification, and an array of laboratory abnormalities. The latter classically include disturbances in the parathyroid hormone/vitamin D axis. More recently, fibroblast growth factor 23 (FGF23) and klotho also ...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2014.02.007
更新日期:2014-03-01 00:00:00
abstract::Acute kidney injury (AKI) represents a common and devastating problem in clinical medicine. A major reason is the lack of early biomarkers for AKI, and hence an unacceptable delay in initiating therapy. Fortunately, the application of innovative technologies has uncovered several novel biomarkers. The most promising o...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2008.05.010
更新日期:2008-09-01 00:00:00
abstract::The very limited ability of adult podocytes to proliferate in vivo is clinically significant because podocytes form a vascular barrier that is functionally critical to the nephron, podocyte hypoplasia is a characteristic of disease, and inadequate regeneration of podocytes is a major cause of persistent podocyte hypop...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2014.06.008
更新日期:2014-07-01 00:00:00
abstract::Sphingolipids, including ceramides, glycosphingolipids, sphingomyelin, and sphingosine-1-phosphate, have been recognized as important molecules that regulate critical cellular functions. Although originally studied in the context of lysosomal storage diseases, the roles of these compounds in more common disorders invo...
journal_title:Seminars in nephrology
pub_type: 杂志文章,评审
doi:10.1016/j.semnephrol.2018.01.007
更新日期:2018-03-01 00:00:00