Abstract 3173: Predictive biomarker evaluation for the anti-cancer imipridone ONC201

MicroRNAs (miRNAs) are small non-coding RNAs that play a pivotal role in many aspects of cell biology, including cancer development. Within esophageal cancer, miRNAs have been proved to be involved in all phases of carcinogenesis, from initiation to metastatic spread. Several miRNAs have been found to be dysregulated in esophageal premalignant lesions, namely Barrett’s esophagus, Barrett’s dysplasia, and squamous dysplasia. Furthermore, numerous studies have investigated the alteration in the expression levels of many oncomiRNAs and tumor suppressor miRNAs in esophageal squamous cell carcinoma and esophageal adenocarcinoma, thus proving how miRNAs are able modulate crucial regulatory pathways of cancer development. Considering these findings, miRNAs may have a role not only as a diagnostic and prognostic tool, but also as predictive biomarker of response to anti-cancer therapies and as potential therapeutic targets. This review aims to summarize several studies on the matter, focusing on the possible diagnostic–therapeutic implications.

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Correlation of MET and PD-L1 expression in malignant melanoma

10.21203/rs.3.rs-22935/v1 ◽

2020 ◽

Author(s):

Kyu Young Song ◽

Sabina Desar ◽

Thomas Pengo ◽

Ryan Shanley ◽

Alessio Giubellino

Keyword(s):

Predictive Biomarker ◽

Human Melanoma ◽

Cancer Therapies ◽

Metastatic Lesions ◽

Melanocytic Lesions ◽

Color Deconvolution ◽

Anti Cancer ◽

Hepatocyte Growth ◽

Melanoma Tissue ◽

Benign Melanocytic Nevi

Abstract Background: The proto-oncogene MET, the hepatocyte growth factor (HGF) receptor, is a transmembrane receptor tyrosine kinase (RTK) with a prominent role in tumor metastasis and resistance to anti-cancer therapies. Melanoma demonstrates relatively frequent MET aberrations, including MET gene amplification. Concurrently, PD-L1, with its ability to evade anti-tumor immune responses, has emerged as a prominent therapeutic target in melanoma and other malignancies and its expression is used as a predictive biomarker of response to immunotherapy. Methods: We performed immunohistochemistry analysis of MET and PD-L1 in 18 human melanoma cell lines derived from both primary and metastatic lesions; we then performed the same analysis in a human melanoma tissue microarray (TMA) containing 100 melanocytic lesions, including 42 cutaneous malignant melanomas, 20 mucosal melanoma, 21 metastatic melanomas and 17 benign melanocytic nevi as controls. After color deconvolution, TMA cores were identified and segmented to isolate staining and calculate the percentage of positive cells in each core. Results: Overall, MET expression was higher in metastatic lesions and it was higher in tumors with increased PD-L1 expression. Moreover, a positive correlation between MET and PD-L1 expression was found in metastatic melanoma. Conclusions: These data suggest that testing for expression of these markers should be conducted in patients with melanoma with metastatic disease and selective therapies targeting these proteins should be considered for advanced disease.

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Abstract A03: Comprehensive predictive biomarker evaluation in two phase II clinical trials of the PI3K/mTOR inhibitor GDC-0980 in metastatic renal cell carcinoma and advanced endometrial cancer

10.1158/1538-8514.pi3k14-a03 ◽

2015 ◽

Author(s):

Jill M. Spoerke ◽

Vicky Makker ◽

Carol Aghajanian ◽

Powles Thomas ◽

Robert J. Motzer ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Trials ◽

Endometrial Cancer ◽

Cell Carcinoma ◽

Renal Cell ◽

Mtor Inhibitor ◽

Predictive Biomarker ◽

Two Phase ◽

Phase Ii Clinical Trials ◽

Biomarker Evaluation

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Macrocytosis as a predictor of response to capecitabine in solid cancers: A meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13080 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13080-e13080

Author(s):

Fahad Almugbel ◽

Laith Al-Showbaki ◽

Michelle Nadler ◽

Alexandra Desnoyers ◽

Ramy Saleh ◽

...

Keyword(s):

Retrospective Cohort ◽

Mean Corpuscular Volume ◽

Meta Analysis ◽

Predictive Biomarker ◽

Negative Association ◽

Hazard Ratios ◽

Inverse Variance ◽

Anti Cancer ◽

Retrospective Cohort Studies ◽

Random Effects Modeling

e13080 Background: Capecitabine is an effective oral chemotherapy that is widely used in a number of solid cancers both as monotherapy or in combination with other anti-cancer drugs. It has been suggested that mean corpuscular volume (MCV) is associated with response to capecitabine. Methods: We searched PubMed for studies exploring the association between capecitabine and macrocytosis or MCV. We extracted the hazard ratios (HR) reporting progression-free (PFS) or overall survival (OS) data when comparing macrocytosis to normal/low MCV. If HR were not directly reported, we estimated them from survival plots using the Parmar method. HR were then pooled in a meta-analysis using generic inverse variance and random effects modeling. Results: Among the 13 identified studies, five were eligible for analysis, comprising a total of 446 patients. One study was a randomized trial and four were retrospective cohort studies. Mean patient age was 53 and cancer sites included breast (n = 226; 50%), colon (n = 131; 29 %) and stomach (n = 89; 19%). Capecitabine was used in combination with other drugs in 64% of patients. There was no association between macrocytosis and PFS (HR 0.91, 0.60-1.38, p = 0.65). Among the 3 studies reporting OS data, there was a significant negative association between macrocytosis and worse OS (HR 1.79, 1.38-2.34, p < 0.001). Conclusions: Macrocytosis in patients treated with Capecitabine was found to have no impact on PFS, but was associated with an inferior OS. This finding suggests that macrocytosis is more likely to be a prognostic factor rather than a predictive biomarker of response to capecitabine.

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Role of chitinase-like proteins in cancer

Biological Chemistry ◽

10.1515/hsz-2015-0269 ◽

2016 ◽

Vol 397 (3) ◽

pp. 231-247 ◽

Cited By ~ 44

Author(s):

Julia Kzhyshkowska ◽

Shuiping Yin ◽

Tengfei Liu ◽

Vladimir Riabov ◽

Irina Mitrofanova

Keyword(s):

Neutralizing Antibodies ◽

Mapk Pathway ◽

Tumor Therapy ◽

Predictive Biomarker ◽

Experimental Models ◽

Cytokines And Chemokines ◽

Anti Cancer ◽

Cancer Outcome ◽

Preclinical Animal Models

Abstract Chitinase-like proteins (CLPs) are lectins combining properties of cytokines and growth factors. Human CLPs include YKL-40, YKL-39 and SI-CLP that are secreted by cancer cells, macrophages, neutrophils, synoviocytes, chondrocytes and other cells. The best investigated CLP in cancer is YKL-40. Serum and plasma levels of YKL-40 correlate with poor prognosis in breast, lung, prostate, liver, bladder, colon and other types of cancers. In combination with other circulating factors YKL-40 can be used as a predictive biomarker of cancer outcome. In experimental models YKL-40 supports tumor initiation through binding to RAGE, and is able to induce cancer cell proliferation via ERK1/2-MAPK pathway. YKL-40 supports tumor angiogenesis by interaction with syndecan-1 on endothelial cells and metastatic spread by stimulating production of pro-inflammatory and pro-invasive factors MMP9, CCL2 and CXCL2. CLPs induce production of pro- and anti-inflammatory cytokines and chemokines, and are potential modulators of inflammatory tumor microenvironment. Targeting YKL-40 using neutralizing antibodies exerts anti-cancer effect in preclinical animal models. Multifunctional role of CLPs in regulation of inflammation and intratumoral processes makes them attractive candidates for tumor therapy and immunomodulation. In this review we comprehensively analyze recent data about expression pattern, and involvement of human CLPs in cancer.

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Correlation of MET and PD-L1 Expression in Malignant Melanoma

Cancers ◽

10.3390/cancers12071847 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1847

Author(s):

Kyu Young Song ◽

Sabina Desar ◽

Thomas Pengo ◽

Ryan Shanley ◽

Alessio Giubellino

Keyword(s):

Predictive Biomarker ◽

Human Melanoma ◽

Cancer Therapies ◽

Metastatic Lesions ◽

Melanocytic Lesions ◽

Programmed Death ◽

Color Deconvolution ◽

Anti Cancer ◽

Hepatocyte Growth ◽

Benign Melanocytic Nevi

The proto-oncogene MET, the hepatocyte growth factor (HGF) receptor, is a transmembrane receptor tyrosine kinase (RTK) with a prominent role in tumor metastasis and resistance to anti-cancer therapies. Melanoma demonstrates relatively frequent MET aberrations, including MET gene amplification. Concurrently, programmed death-ligand 1 (PD-L1), with its ability to evade anti-tumor immune responses, has emerged as a prominent therapeutic target in melanoma and other malignancies and its expression is used as a predictive biomarker of response to immunotherapy. We performed immunohistochemistry analysis of MET and PD-L1 in 18 human melanoma cell lines derived from both primary and metastatic lesions, and in a human melanoma tissue microarray containing one hundreds melanocytic lesions, including primary cutaneous melanomas, primary mucosal melanomas, metastatic melanomas and benign melanocytic nevi as controls. After color deconvolution, each core was segmented to isolate staining and calculate the percentage of positive cells. Overall, MET expression was higher in tumors with increased PD-L1 expression. Moreover, a robust correlation between MET and PD-L1 expression was found in samples from metastatic melanoma and not in primary cutaneous or mucosal melanoma. These data suggest that relative expression levels of these proteins in combination is a marker of advanced disease and testing for expression of these markers should be considered in patients with melanoma.

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Microtubule-Associated Protein ATIP3, an Emerging Target for Personalized Medicine in Breast Cancer

Cells ◽

10.3390/cells10051080 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1080

Author(s):

Maria M. Haykal ◽

Sylvie Rodrigues-Ferreira ◽

Clara Nahmias

Keyword(s):

Breast Cancer ◽

Prognostic Biomarker ◽

Breast Tumors ◽

Predictive Biomarker ◽

Suppressor Gene ◽

Molecular Characteristics ◽

New Era ◽

Candidate Tumor Suppressor Gene ◽

Therapeutic Decisions ◽

Anti Cancer

Breast cancer is the leading cause of death by malignancy among women worldwide. Clinical data and molecular characteristics of breast tumors are essential to guide clinician’s therapeutic decisions. In the new era of precision medicine, that aims at personalizing the treatment for each patient, there is urgent need to identify robust companion biomarkers for new targeted therapies. This review focuses on ATIP3, a potent anti-cancer protein encoded by candidate tumor suppressor gene MTUS1, whose expression levels are markedly down-regulated in breast cancer. ATIP3 is a microtubule-associated protein identified both as a prognostic biomarker of patient survival and a predictive biomarker of breast tumors response to taxane-based chemotherapy. We present here recent studies pointing out ATIP3 as an emerging anti-cancer protein and a potential companion biomarker to be combined with future personalized therapy against ATIP3-deficient breast cancer.

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