Circulating Cell-Free DNA in Renal Cell Carcinoma: The New Era of Precision Medicine

Francini, Edoardo; Fanelli, Giuseppe Nicolò; Pederzoli, Filippo; Spisák, Sándor; Minonne, Erika; Raffo, Massimiliano; Pakula, Hubert; Tisza, Viktória; Scatena, Cristian; Naccarato, Antonio Giuseppe; Loda, Massimo; Nuzzo, Pier Vitale

doi:10.3390/cancers14184359

Cited by 9 publications

(7 citation statements)

References 88 publications

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“…Two patients had a complete response, while two patients had a partial response with elevated levels prior to treatment. Seven patients experienced progressive disease and showed variability in pre-and post-treatment cfDNA levels [179]. Similar outcomes are found in patients treated with ICI.…”

Section: Monitoring Therapeutic Response In Renal Cancer Treatmentsupporting

confidence: 71%

Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer

Chen,

Mihalopoulos,

Zuluaga

et al. 2023

IJMS

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Extracellular vesicles (EVs)—including apoptotic bodies, microvesicles, and exosomes—are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.

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Section: Monitoring Therapeutic Response In Renal Cancer Treatmentsupporting

confidence: 71%

Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer

Chen,

Mihalopoulos,

Zuluaga

et al. 2023

IJMS

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“…Numerous studies have suggested the diagnostic value of methylation markers in RCC [27]. However, to date there are very limited data on the prognostic role of liquid biopsy in RCC.…”

Section: Discussionmentioning

confidence: 99%

Hypermethylated SHOX2 in circulating cell-free DNA post renal cell carcinoma surgery as TNM-independent biomarker for recurrence risk

Büttner

2024

Am J Transl Res

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Introduction: Adjuvant immune checkpoint inhibitor trials in renal cell carcinoma (RCC) call for improved recurrence risk stratification. Due to limitations of circulating tumor DNA (ctDNA) use in RCC, the use of hypermethylated SHOX2 gene (mSHOX2) in circulating cell-free DNA is explored as a surrogate marker for identifying high-risk patients after RCC surgery. Methods: Liquid biopsies were collected post-surgery from 45 RCC patients (mean duration 4.3 days). Real-time polymerase chain reaction was used to analyze SHOX2 methylation in circulating cell-free DNA. Patients were categorized as mSHOX2 positive or negative by cut-off. Metastasis-free survival (MFS), cancerspecific survival (CSS), and overall survival (OS) were assessed using Cox regression and Log-rank analyses (median follow-up time: 60 months). Results: 17 patients were mSHOX2 positive, showing unfavorable OS/CSS (Log-rank P = 0.004 and 0.02) and nearly 6-fold higher recurrence risk (hazard ratio 5.89, 95% CI 1.46-23.8). Multivariable Cox analysis confirmed mSHOX2 as an independent recurrence risk factor, disregarding TNM-based stratification. Conclusions: mSHOX2 effectively identifies high-risk RCC patients post-surgery, indicating minimal residual disease. This easy to implement biomarker has potential for guiding of adjuvant therapy decisions.

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“…Furthermore, kinetic evaluation and molecular profiling through BEAMing (beads, emulsions, amplification, and magnetics), next-generation sequencing (NGS), and digital droplet PCR (ddPCR) are potential non-invasive cancer management modalities. Recently, a surge in cfDNA-based identification of pathological signatures, staging, and development of analytical methods for cancer theranostics with clinical translations has been observed [226,227]. Hence, the significance of cfDNA in cancer diagnosis and precision medicine is underscored by its potential and routine use in the clinical diagnosis and management of several cancers.…”

Section: Theranostic Insights In Tumor-tme-bioenergtics Interfacementioning

confidence: 99%

Cancer Bioenergetics and Tumor Microenvironments—Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems

Farhana

Alsrhani

Khan

et al. 2023

Cancers

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Cancer is an impending bottleneck in the advanced scientific workflow to achieve diagnostic, prognostic, and therapeutic success. Most cancers are refractory to conventional diagnostic and chemotherapeutics due to their limited targetability, specificity, solubility, and side effects. The inherent ability of each cancer to evolve through various genetic and epigenetic transformations and metabolic reprogramming underlies therapeutic limitations. Though tumor microenvironments (TMEs) are quite well understood in some cancers, each microenvironment differs from the other in internal perturbations and metabolic skew thereby impeding the development of appropriate diagnostics, drugs, vaccines, and therapies. Cancer associated bioenergetics modulations regulate TME, angiogenesis, immune evasion, generation of resistant niches and tumor progression, and a thorough understanding is crucial to the development of metabolic therapies. However, this remains a missing element in cancer theranostics, necessitating the development of modalities that can be adapted for targetability, diagnostics and therapeutics. In this challenging scenario, nanomaterials are modular platforms for understanding TME and achieving successful theranostics. Several nanoscale particles have been successfully researched in animal models, quite a few have reached clinical trials, and some have achieved clinical success. Nanoparticles exhibit an intrinsic capability to interact with diverse biomolecules and modulate their functions. Furthermore, nanoparticles can be functionalized with receptors, modulators, and drugs to facilitate specific targeting with reduced toxicity. This review discusses the current understanding of different theranostic nanosystems, their synthesis, functionalization, and targetability for therapeutic modulation of bioenergetics, and metabolic reprogramming of the cancer microenvironment. We highlight the potential of nanosystems for enhanced chemotherapeutic success emphasizing the questions that remain unanswered.

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Circulating Cell-Free DNA in Renal Cell Carcinoma: The New Era of Precision Medicine

Cited by 9 publications

References 88 publications

Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer

Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer

Hypermethylated SHOX2 in circulating cell-free DNA post renal cell carcinoma surgery as TNM-independent biomarker for recurrence risk

Cancer Bioenergetics and Tumor Microenvironments—Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems

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