Renal Carcinoma and Angiogenesis: Therapeutic Target and Biomarkers of Response in Current Therapies

Guillaume, Zoé; Auvray, Marie; Vano, Yann; Oudard, Stéphane; Helley, Dominique; Mauge, Laëtitia

doi:10.3390/cancers14246167

Cited by 13 publications

(8 citation statements)

References 142 publications

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“…These patients often have high-risk features or nonclear cell histology and must be referred for RCC-specific treatments as opposed to the chemotherapy typically used for CUP or gastrointestinal cancer. Furthermore, RCC is highly resistant to systemic chemotherapy and is a highly angiogenic and immunogenic disease (25). Anti-VEGFR TKIs and ICIs are currently the cornerstone treatments for RCC (14).…”

Section: Discussionmentioning

confidence: 99%

Liver Metastases of Unknown Primary Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors: A Case Report and Literature Review

et al. 2023

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Background/Aim: Renal cell carcinoma (RCC) constitutes approximately 3% of all cancers. More than 60% of RCCs are detected incidentally; one-third of patients present with regional or distant metastases, and another 20-40% of patients develop metastases after radical nephrectomy. RCC can metastasize to any organ. In contrast, metastatic RCC (mRCC) without evidence of a primary tumor is extremely rare, with only a few reported cases. Case Report: We present a case of mRCC that initially presented with multiple liver and lymph node metastases but no primary renal lesion. An impressive response to treatment was achieved with a combination of immune checkpoint inhibitors and tyrosine kinase inhibitors. A clinical, radiological, and pathological diagnostic strategy, particularly in the context of a multidisciplinary team, are crucial for reaching a definitive diagnosis. This approach allows to select the appropriate treatment, making a huge difference for a mRCC due to its resistance to standard chemotherapy. Conclusion: There are currently no guidelines available for mRCC without primary tumor. Nevertheless, a combination of TKI and immunotherapy could be the optimal first-line treatment if systemic therapy is required.Renal cell carcinoma (RCC), the most common form of kidney cancer, accounting for approximately 3% of all cancers (1). It affects about 300,000 people worldwide on an annual basis, resulting in over 100,000 deaths. Its incidence is still on the rise, but in recent years a positive trend in 5-year survival has been observed (1). More than 60% of RCCs are detected incidentally, and only 10% of patients exhibit the classic symptoms: hematuria, hip pain, and a distinct mass. Although a significant proportion of patients are considered cured after initial surgery, about 40% of patients will ultimately develop distant metastases (2, 3). Moreover, approximately 20% of patients will present with metastatic RCC (mRCC) at first diagnosis (2, 3). The lungs, lymph nodes, bones, and liver are the organs typically involved in metastatic disease. Moreover, the presence of bone and liver metastases is associated with a poor prognosis for survival (4, 5). In contrast, mRCC without evidence of a primary tumor in the kidney is extremely rare, and only a few cases have been reported in the literature, particularly with multiple upfront liver metastases (6-13).Due to the rarity of occurrence, there are no guidelines for the clinical course and possible strategies, and its management is identical to that of neoplasms with a known primary mass. Several treatments have been indicated in case reports, including surveillance, surgical resection, radiotherapy, and systemic therapy. The clinical scenario for mRCC has dramatically changed over recent years with the emergence of treatments based on the combination of immunotherapy and tyrosine kinase inhibitors (TKIs). These therapies have led to a significant improvement in the response rate, progression-free survival, and overall survival (14).

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Section: Discussionmentioning

confidence: 99%

Liver Metastases of Unknown Primary Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors: A Case Report and Literature Review

et al. 2023

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“…Tumor blood vessel development and vascular network diversity play a crucial role in tumor progression and spread into secondary metastatic foci ( 85 ). Angiogenesis recruits most clear-cell renal cell carcinoma (cc-RCC) blood vessels from peritumor and/or intratumor preexisting vessels ( 87 ). Previous studies have described additional mechanisms of cc-RCC vascularization as vasculogenic mimicry (malignant cells ability to delineate pseudo-vascular structures favouring metastasis) ( 88 , 89 ), and tumor vasculogenesis has also been reported in other malignancies ( 90 – 92 ).…”

Section: Cc-rcc Associated Vasculogenesismentioning

confidence: 99%

Exploring vasculogenesis in the normal human kidney and clear cell renal cell carcinoma: insights from development to tumor progression and biomarkers for therapy response

Cosma,

Fenesan,

Nesiu

et al. 2024

Front. Oncol.

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Vasculogenesis, which refers to the development of blood vessels from precursor cells, is a process that occurs predominantly during early embryonic life. It plays a crucial role in the establishment of the primitive vascular network. Vasculogenesis diminishes throughout the fetal vascular remodeling process, giving way to angiogenesis, which becomes the predominant mechanism after birth. At first, the development of the kidney’s blood vessels depends on vasculogenesis, and then both vasculogenesis and angiogenesis happen simultaneously. Both processes are necessary for the normal development of the renal vasculature. Although the kidneys are highly vascularized, our understanding of normal kidney vasculogenesis is still incomplete. This lack of knowledge may explain the limited data available on the role of vasculogenesis in the progression and spread of renal cancers. In other types of cancer, researchers have well documented the phenomenon of tumor vasculogenesis. However, there is currently limited and fragmented information about the occurrence of clear-cell renal cell carcinomas (cc-RCC). In this article, we provide a comprehensive review of the current understanding of normal kidney vasculogenesis and vasculogenic pathways in clear cell renal cell carcinoma (cc-RCC). We specifically focus on cellular precursors, growth factors, and the influence of the normal and tumor environments on these processes. It will carefully look at how tumor vasculogenesis might affect the growth and metastasis of clear cell renal cell carcinoma (cc-RCC), as well as how it might affect the effectiveness of drugs and the development of therapy resistance.

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“…The adhesion of tumour cells to ECs can induce the generation of secondary tumours, and tumour ECs interact with tumour cells by secreting proteoglycans to accelerate tumour metastasis 12,13 . Aberrant angiogenesis promotes hypoxia and mediates immunosuppression and immune escape 14,15 . Therefore, targeting tumour angiogenesis can be used as a new method for tumour therapy, and ECs, which play an important role, deserve further study.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 Aberrant angiogenesis promotes hypoxia and mediates immunosuppression and immune escape. 14,15 Therefore, targeting tumour angiogenesis can be used as a new method for tumour therapy, and ECs, which play an important role, deserve further study.…”

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confidence: 99%

Construction of endothelial cell signatures for predicting the diagnosis, prognosis and immunotherapy response of bladder cancer via machine learning

Fu,

Sun,

Shi

et al. 2024

J Cellular Molecular Medi

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We subtyped bladder cancer (BC) patients based on the expression patterns of endothelial cell (EC) ‐related genes and constructed a diagnostic signature and an endothelial cell prognostic index (ECPI), which are useful for diagnosing BC patients, predicting the prognosis of BC and evaluating drug sensitivity. Differentially expressed genes in ECs were obtained from the Tumour Immune Single‐Cell Hub database. Subsequently, a diagnostic signature, a tumour subtyping system and an ECPI were constructed using data from The Cancer Genome Atlas and Gene Expression Omnibus. Associations between the ECPI and the tumour microenvironment, drug sensitivity and biofunctions were assessed. The hub genes in the ECPI were identified as drug candidates by molecular docking. Subtype identification indicated that high EC levels were associated with a worse prognosis and immunosuppressive effect. The diagnostic signature and ECPI were used to effectively diagnose BC and accurately assess the prognosis of BC and drug sensitivity among patients. Three hub genes in the ECPI were extracted, and the three genes had the closest affinity for doxorubicin and curcumin. There was a close relationship between EC and BC. EC‐related genes can help clinicians diagnose BC, predict the prognosis of BC and select effective drugs.

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Renal Carcinoma and Angiogenesis: Therapeutic Target and Biomarkers of Response in Current Therapies

Cited by 13 publications

References 142 publications

Liver Metastases of Unknown Primary Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors: A Case Report and Literature Review

Liver Metastases of Unknown Primary Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors: A Case Report and Literature Review

Exploring vasculogenesis in the normal human kidney and clear cell renal cell carcinoma: insights from development to tumor progression and biomarkers for therapy response

Construction of endothelial cell signatures for predicting the diagnosis, prognosis and immunotherapy response of bladder cancer via machine learning

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