PD‐1/PD‐L1 blockade mediates anti‐angiogenic effects by tumor‐derived CXCL10/11 as a potential predictive biomarker

A large proportion of patients with metastatic colorectal cancer (mCRC) experience disease progression after first-line treatment with chemotherapy and bevacizumab, an anti-angiogenic agent, as a result of acquired resistance. However, blocking angiogenesis by targeted therapy towards the vascular endothelial growth factor (VEGF) pathway still forms an essential part of the second-line treatment strategy. Although three approved evidence-based choices for angiogenic agents (continuing treatment with bevacizumab, ramucirumab and aflibercept) are currently available in the second line, making the most effective choice is challenging due to the lack of studies directly comparing these agents. Moreover, despite huge investigational efforts, no predictive biomarker for anti-angiogenic cancer therapies could be identified so far.

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Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2014.12.093 ◽

2015 ◽

Vol 457 (1) ◽

pp. 71-76 ◽

Cited By ~ 11

Author(s):

Atsushi Kasamatsu ◽

Katsuhiro Uzawa ◽

Yasuyuki Minakawa ◽

Shunsaku Ishige ◽

Hiroki Kasama ◽

...

Keyword(s):

Oral Cancer ◽

Predictive Biomarker

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MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Review

Neuro-Oncology ◽

10.1093/neuonc/noab105 ◽

2021 ◽

Author(s):

Sebastian Brandner ◽

Alexandra McAleenan ◽

Claire Kelly ◽

Francesca Spiga ◽

Hung-Yuan Cheng ◽

...

Keyword(s):

Overall Survival ◽

Dna Methyltransferase ◽

Meta Analysis ◽

Alkylating Agents ◽

Cochrane Review ◽

Predictive Biomarker ◽

Test Method ◽

Sufficient Information ◽

Cpg Sites ◽

Hazard Ratios

Abstract BACKGROUND The DNA repair protein O6 methylguanine-DNA methyltransferase (MGMT) causes resistance of tumour cells to alkylating agents. It is a predictive biomarker in high grade gliomas treated with temozolomide, however there is no consensus on which test method, methylation sites, and cut-off values to use. METHODS We performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; where MGMT status was determined in tumour tissue, and assessed by one or more technique; and where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios. Two or more methods were compared in 32 independent cohorts with 3474 patients. RESULTS Methylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP. CONCLUSIONS We cannot draw strong conclusions about use of frozen tissue versus formalin-fixed paraffin embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and Pyrosequencing at CpG sites ranging from 72 to 95. A cut-off threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies. 190 studies were identified presenting hazard ratios from survival analysis in patients in which MGMT methylation was measured by one technique only.

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Residual disease after a neoadjuvant therapy: a strong prognostic and potentially predictive biomarker to personalize therapy

The Breast ◽

10.1016/s0960-9776(21)00082-5 ◽

2021 ◽

Vol 56 ◽

pp. S13-S14

Author(s):

I. Krop

Keyword(s):

Neoadjuvant Therapy ◽

Residual Disease ◽

Predictive Biomarker

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Tumor mutational burden assessment in non-small-cell lung cancer samples: results from the TMB2 harmonization project comparing three NGS panels

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001904 ◽

2021 ◽

Vol 9 (5) ◽

pp. e001904

Author(s):

Javier Ramos-Paradas ◽

Susana Hernández-Prieto ◽

David Lora ◽

Elena Sanchez ◽

Aranzazu Rosado ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Predictive Value ◽

Predictive Biomarker ◽

Small Cell ◽

Small Cell Lung ◽

Mutational Burden ◽

Reproducibility Study ◽

Tumor Mutational Burden

BackgroundTumor mutational burden (TMB) is a recently proposed predictive biomarker for immunotherapy in solid tumors, including non-small cell lung cancer (NSCLC). Available assays for TMB determination differ in horizontal coverage, gene content and algorithms, leading to discrepancies in results, impacting patient selection. A harmonization study of TMB assessment with available assays in a cohort of patients with NSCLC is urgently needed.MethodsWe evaluated the TMB assessment obtained with two marketed next generation sequencing panels: TruSight Oncology 500 (TSO500) and Oncomine Tumor Mutation Load (OTML) versus a reference assay (Foundation One, FO) in 96 NSCLC samples. Additionally, we studied the level of agreement among the three methods with respect to PD-L1 expression in tumors, checked the level of different immune infiltrates versus TMB, and performed an inter-laboratory reproducibility study. Finally, adjusted cut-off values were determined.ResultsBoth panels showed strong agreement with FO, with concordance correlation coefficients (CCC) of 0.933 (95% CI 0.908 to 0.959) for TSO500 and 0.881 (95% CI 0.840 to 0.922) for OTML. The corresponding CCCs were 0.951 (TSO500-FO) and 0.919 (OTML-FO) in tumors with <1% of cells expressing PD-L1 (PD-L1<1%; N=55), and 0.861 (TSO500-FO) and 0.722 (OTML-FO) in tumors with PD-L1≥1% (N=41). Inter-laboratory reproducibility analyses showed higher reproducibility with TSO500. No significant differences were found in terms of immune infiltration versus TMB. Adjusted cut-off values corresponding to 10 muts/Mb with FO needed to be lowered to 7.847 muts/Mb (TSO500) and 8.380 muts/Mb (OTML) to ensure a sensitivity >88%. With these cut-offs, the positive predictive value was 78.57% (95% CI 67.82 to 89.32) and the negative predictive value was 87.50% (95% CI 77.25 to 97.75) for TSO500, while for OTML they were 73.33% (95% CI 62.14 to 84.52) and 86.11% (95% CI 74.81 to 97.41), respectively.ConclusionsBoth panels exhibited robust analytical performances for TMB assessment, with stronger concordances in patients with negative PD-L1 expression. TSO500 showed a higher inter-laboratory reproducibility. The cut-offs for each assay were lowered to optimal overlap with FO.

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