Circulating microRNA-155-3p levels predicts response to first line immunotherapy in patients with metastatic renal cell carcinoma.

Predictive biomarkers of response to immune checkpoint-based therapies (ICI) remain a critically unmet need in the management of advanced renal cell carcinoma (RCC). The complex interplay of the tumour microenvironment (TME) and the circulating immune response has proven to be challenging to decipher. MicroRNAs have gained increasing attention for their role in post-transcriptional gene expression regulation, particularly because they can have immunomodulatory properties. We evaluated the presence of immune-specific extracellular vesicle (EV) microRNAs in the plasma of patients with metastatic RCC (mRCC) prior to initiation of ICI. We found significantly lower levels of microRNA155-3p (miR155) in responders to ICI, when compared to non-responders. This microRNA has unique immunomodulatory properties, thus providing potential biological rationale for our findings. Our results support further work in exploring microRNAs as potential biomarkers of response to immunotherapy.

Primary Mediastinal Germ Cell Tumors: A Thorough Literature Review.

Primary mediastinal germ cell tumors (PMGCTs) are a rare type of cancer affecting young adults. They have different molecular and clinical features compared to testicular germ cell tumors. Non-seminoma PMGCTs have the shortest 5-year overall survival and the poorest prognosis among all of the germ cell tumor presentations, while seminomas share the same survival and prognosis as their testicular counterparts. There is an unmet need for better treatment options for patients with non-seminoma PMGCTs in both first-line and salvage therapy, as the available options are associated with underwhelming outcomes. Identifying biological and genetic factors to predict treatment responses would be helpful in improving the survival of these patients.

Genomic features of mediastinal germ cell tumors: a narrative review.

Background and Objective: Germ cell tumors (GCTs) are uncommon malignancies generally originating from gonads. However, about 5% of GCTs arise outside the gonad (extragonadal), of which 80% develop from the mediastinum. While the prognosis of seminomas is not affected by the gonadal or extragonadal primary location, the prognosis of nonseminoma primary mediastinal GCTs (NS-PMGCTs) is poor, compared to its gonadal counterpart with an estimated 5-year overall survival of about 50%. The current treatments are sub-optimal to increase the cure rate of these rare GCTs. Therefore, molecular insights into these tumors would be valuable to develop novel therapies. The main objective of this review is to describe and dissect the genomic features associated with primary mediastinal GCTs (PMGCTs), highlighting the more frequent genomic alterations and their correlation with clinical outcomes. Methods: We conducted a narrative review of the English literature available in PubMed and Google Scholar between 1982 and 2021, including meta-analyses, systematic reviews, case series and case reports regarding the genomic and clinical features of PMGCTs. We analyzed the available data to describe the molecular characteristics of PMGCTs compared to testicular GCTs (TGCTs), highlighting the most relevant biological and prognostic factors. Key Content and Findings: The high percentage of platinum resistance, the unique association with hematologic malignancies (HMs) and other malignancies, the higher prevalence of P53 mutations, and a distinct genomic landscape characterize this rare disease. Conclusions: Although some studies have unveiled recurrent molecular alterations in PMGCTs, few are particularly suitable for targeted therapy. Due to the rarity of PMGCTs, data sharing and the creation of an international consortium would be helpful to have a better understanding of the molecular drivers of these tumors.

TP53 Alterations Are Associated With Poor Survival in Patients With Primary Mediastinal Nonseminoma Germ Cell Tumors.

BACKGROUND: Primary mediastinal nonseminoma germ cell tumors (PMNSGCT) are a subgroup of nonseminoma germ cell tumors (GCT) with poor prognosis. In this study, PMNSGCT-specific genomic landscape was analyzed and correlated with clinical outcomes. METHODS: DNA was extracted and sequenced from 28 archival tumor tissue of patients with mediastinal GCT (3 seminoma and 25 nonseminoma). Overall survival (OS) and association with gene alterations were estimated using the Kaplan-Meier and univariate Cox regression methods. RESULTS: Three patients (11%) had a karyotype XXY, 17/28 (61%) tumor samples presented chromosome 12p amplification. Somatic mutations were detected in 19/28 (68%) samples. The most frequently mutated genes were: TP53 (13/28; 46%), KIT (5/28; 18%), and KRAS (5/28; 18%). Deleterious TP53 alterations were associated with significantly reduced overall survival (HR: 7.16; P = .012). CONCLUSIONS: TP53 alterations are common in PMNSGCT and are associated with reduced overall survival, potentially underlying the poor sensitivity to chemotherapy observed in these patients.