scholarly journals CMTM6 expression as a potential biomarker for immunotherapy in metastatic renal cell carcinoma

2021 ◽  
Author(s):  
Gennadi Tulchiner ◽  
Andrea Brunner ◽  
Manuela Schmidinger ◽  
Nina Staudacher ◽  
Jacob J. Orme ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Potential Biomarker

A phase Ib study targeting PIM1 and CDK4/6 kinases in metastatic renal cell carcinoma (PICKRCC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS771-TPS771
Author(s):  
Sheldon L. Holder ◽  
Joshua Warrick ◽  
Junjia Zhu ◽  
Joseph J. Drabick ◽  
Monika Joshi
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Dose Escalation Study ◽  
Phase Ib ◽  
Pim1 Kinase ◽  
Potential Biomarker

TPS771 Background: Over the last few years there has been a rapid increase in the clinically relevant agents available to treat metastatic renal cell carcinoma (mRCC). We note, however, that the vast majority of new agents available for mRCC do not exploit new clinical targets or pathways. We believe that the identification of new, clinically relevant targets in RCC will propel the field even further forward, expand treatment options, and lead to improved survival for mRCC patients. SGI-1776, a selective PIM1 kinase inhibitor, has previously been shown to induce reduction in tumor size as monotherapy and in combination with sunitinib in mouse pre-clinical studies of RCC. In our tissue microarray studies a subset of ~26% of RCC showed high staining for PIM1 kinase while only 1% of normal adjacent tissue showed similar high staining. Wildtype PIM1 is constitutively active, thus these data suggest that PIM1 activity is increased in a subset of RCC. Abemaciclib is a potent CDK4/6 inhibitor with an IC50 of 2 and 10 nM, respectively. It is also a potent PIM1 inhibitor with an IC50 of 50 nM. We have shown that abemaciclib decreases cell viability and increases apoptosis in RCC cell lines, and does so at greatest effect in combination with sunitinib. We have also shown that abemaciclib induces regression of RCC tumors in a mouse model of RCC, with the most rapid responses observed when abemaciclib is combined with sunitinib. Based on these data we have opened a phase Ib dose escalation study to determine the safety and tolerability of abemaciclib in combination with sunitinib in patients with mRCC. The study includes an expansion cohort at the recommended phase II dose to evaluate for a signal for efficacy. Pattern and intensity of PIM1 staining in tumor tissue will be evaluated as a potential biomarker of response. We are also collecting blood and urine to evaluate additional potential biomarkers of response. Methods: Clinical trial information: NCT03905889 .[Table: see text]

CMTM6 expression as a potential biomarker for immunotherapy in metastatic renal cell carcinoma

2021 ◽  
Vol 79 ◽  
pp. S746
Author(s):  
G. Tulchiner ◽  
A. Brunner ◽  
M. Schmidinger ◽  
N. Staudacher ◽  
J.J. Orme ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Potential Biomarker

scholarly journals Predicting Response to Immunotherapy in Metastatic Renal Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2662 ◽  
Author(s):  
Matthew D. Tucker ◽  
Brian I. Rini
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Single Gene ◽  
Gene Mutations ◽  
Predictive Biomarkers ◽  
Endogenous Retroviruses ◽  
Aggregate Information ◽  
Potential Biomarker

Immunotherapy-based combinations, driven by PD-1, PD-L1, and CTLA-4 inhibitors, has altered the treatment landscape for metastatic renal cell carcinoma (RCC). Despite significant improvements in clinical outcomes, many patients do not experience deep or lasting benefits. Recent efforts to determine which patients are most likely to benefit from immunotherapy and immunotherapy-based combinations have shown promise but have not yet affected clinical practice. PD-L1 expression via immunohistochemistry (IHC) has shown promise in a few clinical trials, although variations in the IHC assays as well as the use of different values for positivity presents unique challenges for this potential biomarker. Several other candidate biomarkers were investigated including tumor mutational burden, gene expression signatures, single gene mutations, human endogenous retroviruses, the gastrointestinal microbiome, and peripheral blood laboratory markers. While individually these biomarkers have yet to explain the heterogeneity of treatment response to immunotherapy, using aggregate information from these biomarkers may inform clinically useful predictive biomarkers.

Plasma exosome microRNA-155 expression in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors: A potential biomarker of response to systemic therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4570-4570
Author(s):  
Maryam Soleimani ◽  
Marisa Thi ◽  
Neetu Saxena ◽  
Bernhard J. Eigl ◽  
Daniel Joseph Khalaf ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Healthy Volunteers ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Unmet Need ◽  
First Line ◽  
Fuhrman Grade ◽  
Potential Biomarker

4570 Background: The search for a reliable predictive biomarker of response to immune checkpoint-based therapy (ICBT) remains a critically unmet need in the management of metastatic renal cell carcinoma (mRCC). We sought to evaluate the biomarker potential of plasma exosome microRNAs (miRNAs) implicated in RCC and in augmentation of the tumour microenvironment (TME) for such a role. Methods: Eleven miRNAs that are over-expressed in RCC and/or immune-associated were evaluated in 40 patients with mRCC (prior to initiating ICBT) and in 30 healthy volunteers. Exosomes were extracted from 500 uL of plasma and were used for miRNAs extraction. MiRNAs expression was evaluated by RT-PCR. Cycle threshold values were normalized to miR-30-3b, and the relative quantity of the expression (RQ) was compared to those of healthy volunteers and calculated using the 2ΔΔCt method. Mann-Whitney U test was used to evaluate the expression of miRNAs between mRCC pts and healthy volunteers according to best response to first line ICBT between responders (n = 27) v non-responders (n = 13). The cut-off value of significant expression was established by Youden’s index. Responders were defined as those patients experiencing complete response, partial response or stable disease and non-responders were those who experienced progressive disease. Results: The most common first line ICBT was nivolumab + ipilimumab (n = 32), followed by pembrolizumab + axitinib (n = 5), and avelumab + axitinib (n = 3). A significantly higher expression of miRNA-1233 (median 1.85 v 0.81 p = 0.008) and miRNA-155 [miR-155] (3.69 v 0.21 p = 0.006) were found in patients compared to healthy volunteers. Higher miR-155 expression was associated with higher Fuhrman grade (p = 0.002). There was no association with other clinical prognostic factors. MiR-155 was expressed at a significantly lower level in responders than in non-responders (median 0.61 v 35.29, p = 0.042). Response rate amongst patients with low and high expression of miR-155 (RQ ≤ 2.5) was statistically different (p = 0.042) and 84.2% of the pts with low miR-155 expression responded to the treatment. Conclusions: Lower expression of miR-155 was associated with response to ICBT in patients with mRCC. Functionally, miR-155 is involved in regulation and modulation of the TME. These results underscore the need for further work in this area to elucidate the role of this and other miRNAs as biomarkers of response in mRCC.

1103: Laparoscopic Salvage Nephrectomy after Targeted Neoadjuvant Therapy for Metastatic Renal Cell Carcinoma: Initial Results

2007 ◽  
Vol 177 (4S) ◽  
pp. 364-364 ◽  
Author(s):  
Surena F. Matin ◽  
Christopher G. Wood ◽  
Shi-Ming Tu ◽  
Nizar M. Tannir ◽  
Eric Jonasch
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Initial Results
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