The Impact of Tumor Eco-Evolution in Renal Cell Carcinoma Sampling

Abstract

Malignant tumors behave dynamically as cell communities governed by ecological principles. Massive sequencing tools are unveiling the true dimension of the heterogeneity of these communities along their evolution in most human neoplasms, clear cell renal cell carcinomas (CCRCC) included. Although initially thought to be purely stochastic processes, very recent genomic analyses have shown that temporal tumor evolution in CCRCC may follow some deterministic pathways that give rise to different clones and sub-clones randomly spatially distributed across the tumor. This fact makes each case unique, unrepeatable and unpredictable. Precise and complete molecular information is crucial for patients with cancer since it may help in establishing a personalized therapy. Intratumor heterogeneity (ITH) detection relies on the correctness of tumor sampling and this is part of the pathologist’s daily work. International protocols for tumor sampling are insufficient today. They were conceived decades ago, when ITH was not an issue, and have remained unchanged until now. Noteworthy, an alternative and more efficient sampling method for detecting ITH has been developed recently. This new method, called multisite tumor sampling (MSTS), is specifically addressed to large tumors that are impossible to be totally sampled, and represent an opportunity to improve ITH detection without extra costs.

Microbiome within Primary Tumor Tissue from Renal Cell Carcinoma May Be Associated with PD-L1 Expression of the Venous Tumor Thrombus

“…e intravascular portion of the renal tumor is not typically biopsied and would be invasive, which is why we focused on the intratumor microbiota profile. Primary renal tumor tissue can be biopsied, but does suffer from genetic heterogeneity and is one of the controversies regarding renal biopsy accuracy for precision medicine and stratification in clinical trials [21][22][23].…”

Overexpression of PKMYT1 Facilitates Tumor Development and Is Correlated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

“…In addition, approximately 30% of patients who have localized ccRCC experience recurrence or metastasis after tumor-targeted surgery [ 7 , 8 ]. Thus, it is essential to further investigate reliable ccRCC-associated molecular biomarkers, thereby facilitating early diagnosis, monitoring of tumor development, and discovery of novel therapeutic targets [ 9 ].…”

Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines

“…However, for the management of recurrent or metastatic ccRCC, targeted drug therapy is preferred; this includes the use of tyrosine kinase inhibitors such as sunitinib, sorafenib, axitinib and pazopanib; mammalian target of rapamycin (mTOR) inhibitors such as temsirolimus and everolimus; and monoclonal antibodies such as bevacizumab, which targets vascular endothelial growth factor (VEGF) [9,10]. In addition to tyrosine kinase inhibitors, immunotherapy using nivolumab and interferon-α are considered to be the standard treatment strategies [11,12]. However, ccRCC gradually develops resistance to chemotherapy and other treatment modalities such as hormonal therapy and radiotherapy; hence, there is a tremendous need for the advancement of new therapeutic alternatives [13].…”