Biomarkers in Genitourinary Cancers, Volume I

project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB.Genitourinary cancers are known as significant causes of mortality worldwide. This heterogeneous group includes, among others, the most common cancer in men, prostate cancer, the most common form of kidney cancer, renal cell carcinoma (RCC), and the 10th most common cancer, bladder cancer. These entities present biological diversity with various histological subtypes and a poor prognosis when metastatic. There has been considerable progress in treating patients with genitourinary cancers due to the improved understanding of their pathological mechanisms and the identification of meaningful biomarkers. The treatment progress has led to a fundamental paradigm shift in treatments. For example, our current understanding of the immunogenicity of these tumours has improved tremendously. Thanks to that, today, immunotherapy is a reliable strategy to improve the outcomes of patients with metastatic urothelial carcinoma, renal cell carcinoma, and prostate cancer. However, there is still a critical need to enrich our understanding of additional molecular mechanisms. Along with the mechanisms, there is an urgent requirement to identify novel biomarkers to progress the diagnosis and prognosis of genitourinary cancers and their treatment. Biomarkers have become a significant focus of research, primarily on how they can help predict response to systemic therapy, identify treatment resistance, and avoid toxicities. Biomarkers that reveal the mutated tumour suppressor genes, the altered signalling pathways and the aberrantly expressed molecules help select potentially responsive patients to a given therapy. In this way, biomarkers improve outcomes and reduce costs related to ineffective treatments, and, most importantly, they significantly upsurge patients’ quality of life. This Research Topic named Biomarkers in Genitourinary Cancers includes an interesting and up to date palette of publications from prominent research and clinical groups focused on identifying significant and emerging prognostic and predictive biomarkers. These biomarkers encompass non-coding RNA, serum proteins, gene expression, and glycans, among other entities identified in patients’ cohorts, samples and in the increasing number of public databases.publishersversionpublishe

Systemic Treatment for Advanced and Metastatic Non-Clear Cell Renal Cell Carcinoma: Examining Modern Therapeutic Strategies for a Notoriously Challenging Malignancy

Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group of malignancies that represents 25% of renal cell carcinoma (RCC) cases. Treatment for non-clear cell histologies is mostly based on evidence from small phase II clinical trials or extrapolated from successful therapies in clear cell RCC because of the low incidence of non-clear cell pathology. Advances in genomic profiling have improved clinicians’ understanding of molecular targets for nccRCC, such as altered mesenchymal epithelial transition (MET) gene status and fumarate hydratase (FH) gene inactivation, but patient outcomes remain poor and optimal management of this disease remains unclear. This review assesses outcomes by histologic subtype from 27 prospective and 13 ongoing clinical trials to identify therapeutic strategies for advanced or metastatic nccRCC. Vascular endothelial growth factor tyrosine kinase inhibitors (TKI), such as sunitinib, and mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, have demonstrated efficacy and remain viable treatment options, with a preference for sunitinib. However, everolimus is preferred in patients with chromophobe RCC because folliculin (FLCN) gene mutations upregulate the mTOR pathway. Novel TKIs, such as cabozantinib, show improved outcomes in patients with papillary RCC because of targeted MET inhibition. Platinum-based chemotherapy continues to be the recommended treatment strategy for collecting duct and medullary RCC. Clinically meaningful antitumor activity has been observed across all non-clear cell histologies for immune checkpoint inhibitors, such as nivolumab, pembrolizumab, and ipilimumab. Ongoing trials are evaluating novel tyrosine kinase inhibitor and immunotherapy combination regimens, with an emphasis on the promising MET-inhibitor cabozantinib and pembrolizumab plus lenvatinib

Different frequencies of RIP among early vs. late ascospores of Neurospora crassa

We have noticed that the frequency of RIP can be quite variable, even in crosses of the same strains. One possible source of variability is the time at which ascospores are harvested. We reasoned that the earliest ascospores shot from a perithecium might contain DNA that went through relatively few mitotic divisions in pre-meiosis. RIP occurs between fertilization and premeiotic DNA synthesis (Selker et al. 1987 Cell 51:741-752). Thus, early spores might have less exposure to RIP than late spores. Since all ascospores from a perithecium are thought to arise from a single fertilization event, a minimum of 7- 10 divisions are required to account for the number of ascospores normally produced (Perkins and Barry, 1977 Adv. Genet. 211:541-544). It is likely, however, that some ascospore lineages contain fewer divisions than others

An Uncommon Case of Sinonasal Adenoid Cystic Carcinoma Metastatic to the Kidney Treated with Metastasectomy

Adenoid cystic carcinoma (ACC) is a rare tumor, accounting for 1% of all head and neck cancers, with an aggressive nature characterized by local recurrence, delayed metastasis, and survival of less than 50% at 10 years. This is a case of biopsy-proven ACC to the kidney, 1 of 29 known occurrences, managed by metastasectomy by robotic-assisted nephrectomy, with plans for resection of lung metastasis. Thirteen years after diagnosis of sinonasal ACC treated with resection, the patient presented with shortness of breath. This prompted a CT scan of the chest, which led to the incidental finding of left renal mass and pulmonary lesion. Literature suggests improved disease-specific survival in locoregional recurrence treated with surgery versus radiation; in patients with metastasis to the lung, metastasectomy offers greater survival benefit than supportive therapy. But, this is not significantly better than chemotherapy or radiation alone. While the optimal therapeutic approach remains to be identified in distant metastatic ACC, metastasectomy remains a viable option for patients who have potentially completely resectable metastatic tumors, appropriate performance status, and adequate affected-organ function. Preoperative counseling should include discussion on partial nephrectomy with prioritization of nephron-sparing but potential for increased perioperative risk versus radical nephrectomy to ensure negative margins and expedite timeline to systemic therapy

Familial Renal Cancer: Molecular Genetics and Surgical Management

Familial renal cancer (FRC) is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted molecular treatments for patients affected by systemic disease. As a result, the treatments for families affected by von Hippel-Lindau (VHL), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis renal cell carcinoma (HLRCC), and Birt-Hogg-Dubé (BHD) are rapidly changing. We review the genetics and contemporary surgical management of familial forms of kidney cancer

Nonequivalent effects of PKC activation by PMA on murine CD4 and CD8 cell‐surface expression

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154260/1/fsb2002012010.pd