Treatment Of Kidney Cancer Research Articles

Melatonin as a potential inhibitor of kidney cancer: A survey of the molecular processes.

Studies have shown that despite the decreasing mortality rates of kidney cancer patients, its incidence is increasing. Therefore, a comprehensive re-evaluation of treatment options is necessary to provide appropriate treatments for the increasing number of patients. Moreover, the side effects caused by surgery, which is the main treatment of this disease, may lead to higher morbidity rates. Consequently, new safer approaches must be examined and considered. Major advancements have been made in the field of targeted agents as well as treatments based on immunotherapy since renal cell carcinoma (RCC) does not respond well to chemotherapy. While the therapeutic options for this cancer are increasing, the resulting complexity of selecting the best strategy for treating the patients is daunting. Moreover, each therapeutic option must be evaluated concerning toxicity, cost, and clinical advantages. Several characteristics, which are beneficial for cancer therapies have been attributed to melatonin. For decades, investigations have explored the application of melatonin in the treatment of cancer; insufficient attention has been paid to this molecule at the clinical level. Melatonin plays a role in cancer therapy due to its anti-tumor effects as well as by enhancing the efficacy of other drugs as an adjuvant. In this review, we discuss different roles of melatonin in the treatment of kidney cancer. The studies concerned with the applications of melatonin as an adjuvant in the immunotherapy of patients with kidney cancer are summarized. Also, we highlight the apoptotic and anti-angiogenic effects of melatonin on renal cancer cells which are mediated by different molecules (e.g., HIF-1 and VEGF, ADAMTS1, and MMP-9) and signaling pathways (e.g., P56, P52, and JNK). Furthermore, we take a look into available data on melatonin's ability to reduce the toxicities caused by kidney carcinogens, including ochratoxin A, potassium bromate, and Fe-NTA.

Counterbalancing COVID-19 with Cancer Surveillance and Therapy: A Survey of Patients with Renal Cell Carcinoma

BackgroundWhile providers are challenged with treatment decisions during the coronavirus disease 2019 (COVID-19) crisis, decision making ultimately falls in the hands of patients—at present, their perspective is poorly understood. ObjectiveTo ascertain renal cell carcinoma (RCC) patients’ perspectives on COVID-19 and understand the associated implications for treatment. Design, setting, and participantsAn online survey of RCC patients was conducted from March 22 to March 25, 2020, disseminated through social media and patient networking platforms. The survey comprised 45 items, including baseline demographic, clinicopathologic, and treatment-related information. Patients were additionally queried regarding their anxiety level related to COVID-19 and associated implications for their cancer diagnosis. InterventionAn online survey study. Outcome measurements and statistical analysisDescriptive statistics with graphical outputs were used to characterize survey results. Results and limitationsA total of 539 patients (male:female 39%:58%) from 14 countries responded. Of them, 71% felt that their risk of COVID-19 infection was higher than the general population, and 27% contacted their physician to establish this. Among patients with localized disease (40%), most (42%) had scheduled surveillance scans within 6 wk–65% were unwilling to delay scans. Among patients with metastatic disease, 76% were receiving active therapy. While most patients preferred not to defer therapy (51%), patients receiving immune therapy regimens were less amenable to deferring therapy than those receiving targeted treatment (20% vs 47%). ConclusionsDespite high levels of anxiety surrounding COVID-19, many patients with RCC were inclined to adhere to existing schedules of surveillance (localized disease) and systemic treatment (metastatic disease). Patient summaryThe coronavirus disease 2019 (COVID-19) pandemic has prompted many doctors to develop different treatment strategies for cancer and other chronic conditions. Given the importance of the patient voice in these strategies, we conducted a survey of patients with kidney cancer to determine their treatment preferences. Our survey highlighted that most patients prefer to continue their current strategies of kidney cancer treatment and monitoring.

The Immunotherapy Revolution in Kidney Cancer Treatment: Scientific Rationale and First-Generation Results.

The recent discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, including the treatment for renal cell carcinoma (RCC). Following the eras of cytokines and molecularly targeted therapies including vascular endothelial growth factor-directed agents and mammalian target of rapamycin (mTOR) inhibitors, ICIs have become the latest addition to the RCC armamentarium. To understand the scientific rationale behind this revolution in RCC treatment, we have reviewed the fundamental discoveries underlying the transition from old (cytokines) to new (ICIs) immunotherapies. We summarize the pivotal trials (CheckMate 025, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, IMmotion151) of checkpoint inhibitors for clear cell RCC in various treatment settings. With the availability of many different combination therapies and many more currently under investigation, clear cell RCC treatment is becoming more complex. Patient preferences, disease volumes, and adverse event profiles are essential in determining which option is the best for an individual patient. In the future, biomarkers currently under development could guide these treatment decisions.

ELA/APELA precursor cleaved by furin displays tumor suppressor function in renal cell carcinoma through mTORC1 activation.

Apelin is a well-established mediator of survival and mitogenic signaling through the apelin receptor (Aplnr) and has been implicated in various cancers; however, little is known regarding Elabela (ELA/APELA) signaling, also mediated by Aplnr, and its role and the role of the conversion of its precursor proELA into mature ELA in cancer are unknown. Here, we identified a function of mTORC1 signaling as an essential mediator of ELA that repressed kidney tumor cell growth, migration, and survival. Moreover, sunitinib and ELA showed a synergistic effect in repressing tumor growth and angiogenesis in mice. The use of site-directed mutagenesis and pharmacological experiments provided evidence that the alteration of the cleavage site of proELA by furin induced improved ELA antitumorigenic activity. Finally, a cohort of tumors and public data sets revealed that ELA was only repressed in the main human kidney cancer subtypes, namely clear cell, papillary, and chromophobe renal cell carcinoma. Aplnr was expressed by various kidney cells, whereas ELA was generally expressed by epithelial cells. Collectively, these results showed the tumor-suppressive role of mTORC1 signaling mediated by ELA and established the potential use of ELA or derivatives in kidney cancer treatment.

Multidisciplinary Management of Advanced Kidney Cancer

A number of therapeutic options are available for the treatment of advanced kidney cancer, including targeted therapy, immunotherapy, and nephrectomy. Choice of therapy for advanced kidney cancer is guided by risk stratification. Immunotherapy combinations are generally superior to vascular endothelial growth factor -based monotherapy, and overall survival rates continue to increase substantially. With new systemic therapy options, additional improvements have been noted in durable responses to treatment and in quality of life. Nephrectomy remains an important consideration in selected patients, particularly those with minimal burden of metastatic disease. Managing the adverse events of treatment of advanced kidney cancer requires close attention and multidisciplinary collaboration.

38 - Surgical complications of kidney cancer treatment: Using French database PMSI 2016-2017

38 - Surgical complications of kidney cancer treatment: Using French database PMSI 2016-2017

Predictive Markers of First Line Pazopanib Treatment in Kidney Cancer

Real-world evidence from clinical practices is fundamental for understanding the efficacy and tolerability of medicinal products. Patients with renal cell cancer were studied to gain data not represented by analyses conducted on highly selected patients participating in clinical trials. Our goal was to retrospectively collect data from patients with advanced renal tumours treated with pazopanib (PZ) to investigate the efficacy, frequency of side effects, and searching for predictive markers. Eighty-one patients who had received PZ therapy as first-line treatment were retrospectively evaluated. Overall survival (OS), progression-free survival (PFS) were assessed as endpoints. Median PFS and OS were 11.8 months (95% CI: 8.8–22.4); and 30.2 months (95% CI: 20.3–41.7) respectively. Severe side effects were only encountered in 11 (14%) patients. The presence of liver metastasis shortened the median PFS (5.5 vs. 14.8 months, p = 0.003). Median PFS for patients with or without side effects was 25.6 vs. 7.3 months, respectively (p = 0.0001). Patients younger than 65 years had a median OS of 41.7 months vs. 25.2 months for those over 65 years of age (p = 0.008). According to our results absence of liver metastases, younger age (<65 years) and presence of side effects proved to be independent predictive markers of better PFS and OS.

Crosstalk between TGF-β1 signalling pathway and microRNAs in renal cancer

Alterations in TGF-β1 signalling in renal cancer are accompanied by disturbed expression of microRNAs (miRNAs). TGF-β1 is an important regulator of key cellular processes and contributes to the development of many diseases, including cancer. At early cancer stages, TGF-β1 inhibits proliferation and tumour growth, while as the disease progresses, TGF-β1 stimulates metastasis. This dual TGF-β1 effect in cancers is called the “TGF-β1 paradox”. miRNAs – small, noncoding RNAs which regulate genes expression may contribute to the switching of TGF-β1 from suppressor to oncogenic function. The article presents the latest information regarding mutual regulation between miRNAs and the TGF-β1 signalling pathway as well as its potential role in the treatment of kidney cancer.

Assessment of complications after laparoscopic surgery of kidney tumors using Clavien-Dindo classification.

&lt;b&gt;Introduction:&lt;/b&gt; Surgical procedures are accepted, basic method of treating kidney cancer. &lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; The aim of the study was to assess postoperative complications according to the Clavien-Dindo classification after laparoscopic procedures in the treatment of kidney cancer. &lt;br&gt;&lt;b&gt;Material and methods: &lt;/b&gt;A retrospective study involved 112 patients. The research was based on the analysis of data from the medical records of the clinic and the documentation of the urological polyclinic. Classification of postoperative complications according to Clavien and Dindo in the operated patients was assessed on a 7-point scale. &lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; Less severe complications occurred in 24 patients (21.4%). All the above-mentioned TNMtransfusions. Grade IIIb complication occurred in one patient (0.9%) and required kidney removal. &lt;br&gt;&lt;b&gt;Conclusions: &lt;/b&gt;The use of the Clavien-Dindo classification in the assessment of postoperative complications of laparoscopic renal procedures is a simple and objective diagnostic tool for establishing the postoperative condition of patients. The results of our examination of complications after laparoscopic renal surgery according to the Clavien-Dindo classifications are similar to those obtained in renowned urological centers.

PD1 and PD-L1 Inhibitors for the Treatment of Kidney Cancer: The Role of PD-L1 Assay.

Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway represent a drastic change in the treatment landscape of RCC resulting in a dynamic and evolving scenario. There is an urgent need for predictive biomarkers of response to provide a personalized therapeutic strategy for individual patients. In this review, we focused on trials that investigated the administration of a PD-1 and PDL1 inhibitor alone or in combination with another agent and compared the different assays applied in each trial to evaluate the role of PD-L1 as a prognostic and predictive biomarker. So far, the use of PD-L1 expression alone is not sufficient to predict treatment response and present many limitations: the lack of consensus between different methodologies on biomarker assessment, the heterogeneity of PD-L1 between primary tumors and metastatic sites, different criteria of response to therapy (RECIST vs. irRECIST), the complex interplay with inflammatory components, previous treatments, administration of antibiotic therapy. Combinations of different biomarkers and biological features, such as gene expression associated with angiogenesis, immune response and myeloid inflammation are promising biological variables that need to be validated in the context of prospective clinical trials.

Preparation, Characterization, and Evaluation of Cisplatin-Loaded Polybutylcyanoacrylate Nanoparticles with Improved In Vitro and In Vivo Anticancer Activities.

This study aimed to evaluate the therapeutic efficacy of the cisplatin encapsulated into polybutylcyanoacrylate (PBCA) nanoparticles for the treatment of kidney cancer. The nanoformulation was successfully developed using the miniemulsion polymerization method and characterized in terms of size, size distribution, drug loading and encapsulation efficiencies, drug release behavior, in vitro cytotoxicity effects, in vivo toxicity, and therapeutic effects. Cisplatin-loaded PBCA nanoparticles were confirmed to be in nanoscale with the drug entrapment efficiency of 23% and controlled drug release profile, in which only 9% of the loaded drug was released after 48 h. The nanoparticles caused an increase in the cytotoxicity effects of cisplatin against renal cell adenocarcinoma cells (ACHN) (2.3-fold) and considerably decreased blood urea nitrogen and creatinine concentrations when compared to the standard cisplatin (1.6-fold and 1.5-fold, respectively). The nanoformulation also caused an increase in the therapeutic effects of cisplatin by 1.8-fold, in which a reduction in the mean tumor size was seen (3.5 mm vs. 6.5 mm) when compared to the standard cisplatin receiver rats. Overall, cisplatin-loaded PBCA nanoparticles can be considered as a promising drug candidate for the treatment of kidney cancer due to its potency to reduce the side effects of cisplatin and its toxicity and therapeutic effects on cancer-bearing Wistar rats.

Advances in Combination Therapy of Immune Checkpoint Inhibitors for Lung Cancer

检查点抑制剂（immune checkpoint inhibitors, ICIs）治疗是目前最常用的免疫治疗方案，已被批准用于黑色素瘤、肾癌、头颈癌、膀胱癌等多种肿瘤的临床治疗，在肺癌治疗中更是取得突破性进展，成为肺癌综合治疗的新支柱。但由于肿瘤的异质性及肿瘤微环境的复杂性，ICIs单药在非选择患者中有效率偏低。手术、化疗、放疗、靶向治疗等治疗手段可与免疫治疗产生协同作用，联合疗法成为目前探索的热点。本文着重于免疫检查点抑制剂联合治疗策略的研究进展，并描述了免疫疗法如何被用于早期癌症的治疗。

Checkpoint inhibitor immunotherapy in kidney cancer.

Kidney cancer has unique features that make this malignancy attractive for therapeutic approaches that target components of the immune system. Immune checkpoint inhibition is a well-established part of kidney cancer treatment, and rapid advances continue to be made in this field. Initial preclinical studies that elucidated the biology of the programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) immune checkpoints led to a series of clinical trials that resulted in regulatory approval of nivolumab and the combination of ipilimumab plus nivolumab for the treatment of advanced renal cell carcinoma. Subsequent data led to approvals of combination strategies of immune checkpoint inhibition plus agents that target the vascular endothelial growth factor receptor anda shift in the current standard of renal cell carcinoma care. However, controversies remain regarding the optimal therapy selection and treatment strategy for individual patients, which might be eventually overcome by current intensive efforts in biomarker research. That work includes evaluation of tumour cell PD-L1 expression, gene expression signatures, CD8+ T cell density and others. In the future, further advances in the understanding of immune checkpoint biology might reveal new therapeutic targets beyond PD-1, PD-L1 and CTLA-4, as well as new combination approaches.

Robotic versus open urological oncological surgery: study protocol of a systematic review and meta-analysis

IntroductionMinimally invasive surgery in urology has grown considerably in application since its initial description in the early 1990s. Herein, we present the protocol for a systematic review and meta-analysis comparing...

SEOM clinical guideline for treatment of kidney cancer (2019)

In this article, we review de state of the art on the management of renal cell carcinoma (RCC) and provide recommendations on diagnosis and treatment. Recent advances in molecular biology have allowed the subclassification of renal tumours into different histologic variants and may help to identify future prognostic and predictive factors. For patients with localized disease, surgery is the treatment of choice with nephron-sparing surgery recommended when feasible. No adjuvant therapy has demonstrated a clear benefit in overall survival. Considering the whole population of patients with advanced disease, the combination of axitinib with either pembrolizumab or avelumab increase response rate and progression-free survival, compared to sunitinib, but a longer overall survival has only been demonstrated so far with the pembrolizumab combo. For patients with IMDC intermediate and poor prognosis, nephrectomy should not be considered mandatory. In this subpopulation, the combination of ipilimumab and nivolumab has also demonstrated a superior response rate and overall survival vs. sunitinib. In patients progressing to one or two antiangiogenic tyrosine-kinase inhibitors, both nivolumab and cabozantinib in monotherapy have shown benefit in overall survival compared to everolimus. Although no clear sequence can be recommended, medical oncologists and patients should be aware of the recent advances and new strategies that improve survival and quality of life in patients with metastatic RCC.

Stereotactic Body Radiation Therapy for the Definitive Treatment of Early Stage Kidney Cancer: A Survival Comparison With Surgery, Tumor Ablation, and Observation

PurposePartial nephrectomy is the preferred definitive treatment for early stage kidney cancer, with tumor ablative techniques or active surveillance reserved for patients not undergoing surgery. Stereotactic body radiation therapy (SBRT) has emerged as a potential noninvasive alternative for patients with early stage kidney cancer not amenable to surgery, with early reports suggesting excellent rates of local control and limited toxicity. Methods and MaterialsThe national cancer database from 2004 to 2014 was queried for patients who received a diagnosis of T1N0M0 kidney cancer. Treatments were categorized as surgery (partial or total nephrectomy), tumor ablation (cryoablation or thermal ablation), SBRT (radiation therapy in 5 fractions or less to a total biological effective dose [BED10] of 72 or more), or observation. A propensity score was generated by multinomial logistic regression. A Cox proportional hazards model was fit to determine association between overall survival and treatment group with propensity score adjustments for patient, demographic, and treatment characteristics. ResultsA total of 165,298 received surgery, 17,196 underwent tumor ablation, 104 underwent SBRT, and 18,241 were observed. Median follow-up was 51 months. On multivariable analysis, surgery, tumor ablation, and SBRT were associated with a decreased risk of death compared with observation, with hazard ratios of 0.25 (95% confidence interval, 0.24-0.26, P < .001), 0.36 (0.35-0.38, P < .001), and 0.56 (0.39-0.79, P < .001), respectively. When stratifying by BED10 and compared with observation, hazard ratio for risk of death for patients treated with SBRT to a BED10 ≥100 (n = 62) and a BED10 <100 (n = 42) was 0.34 (0.19-0.60, P < .001) and 0.90 (0.58-1.4, P = .64), respectively. ConclusionsIn this population-based cohort, patients undergoing high-dose SBRT (BED10 ≥100) for early stage kidney cancer demonstrated longer survival compared with patients undergoing observation. This may be a promising noninvasive treatment option for nonsurgical candidates with prospective efficacy and safety assessments meriting study in future clinical trials.

Current advances in kidney cancer immunotherapy

In Russia, among tumors of the genitourinary system, renal cell carcinoma takes the 2nd place after prostate cancer. In 25 % of patients at the time of diagnosis, metastases are detected. Treatment of advanced stages of renal cell carcinoma is often not effective enough. The introduction into clinical practice of modern immunotherapeutic drugs based on inhibition of immune check points has changed the prognosis of the disease for many patients with various malignant neoplasms, including kidney cancer. In this article, we described the results of recent clinical trials on the use of immunotherapy in the treatment of kidney cancer. The most effective is combination of drugs that inhibit different immune check points, and a combination of a check point inhibitor with a targeted drug. This approach is likely to be a major one in the treatment of renal cell carcinoma in the short term. Combinations of control point inhibitors with radiation therapy and immunomodulatory drugs, the role of miRNAs in the regulation of expression of immune control points, the significance and characteristics of the microbiome in connection with the success of immunotherapy for kidney cancer, gene expression profiles as biomarkers of the immune response, and other biomarkers are considered. A better understanding of the mechanisms that limit the effectiveness of immune control point inhibitors will improve future treatment.

Perspectives From an Onconephrology Interest Group: Conference Report.

Introduction and objective:Onconephrology is a new and evolving field that deals with kidney complications in patients with cancer as well as the management of cancer in patients with preexisting kidney disease. With increasing numbers of patients with cancer with kidney-related complications, the field has garnered increased attention. Thus, an annual Greater Toronto Area Onconephrology Interest Group symposium was held in May 2019. The objective of the meeting was to demonstrate the junctures between oncology and nephrology by highlighting recent data regarding (1) kidney impairment in solid organ malignancies, (2) management and treatment of kidney cancer, (3) kidney impairment in hematologic malignancies, (4) malignancy and kidney transplantation, and (5) hyponatremia in patients with cancer.Methods and sources of information:Through a structured presentation, the group explored key topics discussed at a Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Onconephrology. Expert opinions, clinical trial findings, and publication summaries were used to illustrate patient and treatment-related considerations in onconephrology.Key findings:Kidney complications in patients with cancer are a central theme in onconephrology. An estimated 12% to 25% of patients with solid organ malignancies have chronic kidney disease (CKD), although in certain cancers, the prevalence of CKD is higher. Kidney impairment is also a common complication of some hematologic malignancies. The incidence of renal failure in patients with multiple myeloma is estimated at 18% to 56% and light chain cast nephropathy is seen in approximately 30% of these patients. In addition, there appears to be a bidirectional relationship between kidney cancer and CKD, with some data sets suggesting the risk increases as kidney function declines. Cancer is also of concern in patients with preexisting kidney disease. Kidney transplant recipients have a greater risk of cancer and a higher risk of cancer-related mortality. Kidney complications have also been associated with novel cancer therapies, such as immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy. An estimated 2% to 4% of patients initiating an immune checkpoint inhibitor may develop nephrotoxicity, whereas up to 40% of patients on CAR T-cell therapy experience cytokine release syndrome (CRS). Tumor lysis syndrome and electrolyte abnormalities, such as hyponatremia, have also been reported with CAR T-cell therapy. While the incidence and prevalence of hyponatremia vary depending on the cancer type and serum sodium cutoff point, hyponatremia may be seen in up to 46% of patients hospitalized in cancer centers.Conclusions:Onconephrology is a developing field and the themes arising from this meeting indicate a need for greater collaboration between oncologists and nephrologists. Educational symposia and onconephrology fellowship programs may allow for improved cancer care for patients with kidney disease.

Colonic Perforation Associated with Necrotizing Fasciitis in a Patient Receiving Tyrosine Kinase Inhibitor (Pazopanib) for Recurrent Retroperitoneal Renal Cell Carcinoma

Pazopanib, under the trade name of votrient, is a potent tyrosine-kinase growth factor receptor inhibitor used in the treatment of late-stage kidney cancer and soft tissue sarcoma. Rarely this drug has been associated with gastrointestinal perforations; however, prior studies have not shown an association with necrotizing fasciitis. We present a case of suspected pazopanib-induced extensive colonic perforation resulting in a severe necrotizing fasciitis. As this is a potentially rare complication of this targeted therapy, our goal is to heighten the awareness of colonic perforation as it is only seen in 0.9% of patients on pazopanib. The staged operative management and multidisciplinary approach throughout this patient’s care allowed for complete recovery from a life-threatening diagnosis. J Curr Surg. 2020;10(3):54-58 doi: https://doi.org/10.14740/jcs416

Preparation of AS1411 Aptamer Modified Mn-MoS2 QDs for Targeted MR Imaging and Fluorescence Labelling of Renal Cell Carcinoma.

BackgroundEarly diagnosis of renal cell carcinoma is extremely significant for the effective treatment of kidney cancer. The development of AS1411 aptamer modified Mn-MoS2 QDs provides a promising fluorescence/magnetic resonance (MR) dual-modal imaging probe for the precise diagnosis of renal clear cell carcinoma.MethodsIn this work, Mn-MoS2 QDs were synthesized through a simple “bottom-up” one-step hydrothermal method. AS1411 aptamer was modified on the Mn-MoS2 QDs to improve the specificity to renal cell carcinoma. The characteristics of Mn-MoS2 QDs were confirmed by transmission electronic microscopy (TEM), atomic force microscope (AFM), X-ray photoelectron spectrometer (XPS), photoluminescence (PL) emission spectra, etc. Cellular fluorescence labelling was investigated using the Mn-MoS2 QDs and AS1411-Mn-MoS2 QDs. The T1-weighted MR imaging was assessed by the in vitro MR cell imaging and in vivo MR imaging. Finally, the long-term toxicity of Mn-MoS2 QDs was investigated by the hematology and histological analysis.ResultsThe prepared Mn-MoS2 QDs exhibited excellent aqueous property, intense fluorescence, low toxicity, high quantum yield of 41.45% and high T1 relaxivity of 16.95 mM−1s−1. After conjugated with AS1411 aptamer, the AS1411-Mn-MoS2 QDs could specifically fluorescently label the renal carcinoma cells and present a specific MRI signal enhancement in the tumor region of mice bearing renal carcinoma tumors. Furthermore, Mn-MoS2 QDs revealed low toxicity to the mice via hematology and histological analysis.ConclusionThese results demonstrated the potential of AS1411-Mn-MoS2 QD as a novel nanoprobe for targeted MR imaging and fluorescence labelling of renal cell carcinoma.