Peter Danenberg

Peter Danenberg
University of Southern California | USC · Department of Biochemistry and Molecular Biology

Ph.D.

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330
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Introduction
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Publications

Publications (330)
Article
Background Few prospective studies have used liquid biopsy testing in RAS-mutant metastatic colorectal cancer (mCRC), and its clinical significance remains unknown. Therefore, this study aimed to carry out a biomarker analysis by liquid biopsy using updated data of the phase II trial of FOLFOXIRI plus bevacizumab as first-line chemotherapy for RAS-...
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Rarely, scientific developments centered around the patient as a whole are published. Our multidisciplinary group, headed by gastrointestinal surgeons, applied this research philosophy considering the most important aspects of the diseases "colon- and rectal cancer" in the long-term developments. Good expert cooperation/knowledge at the Comprehensi...
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Aim: We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer (CRC). An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort. Methods: Blood samples were coll...
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TPS3621 Background: A randomized phase II trial, DEEPER (JACCRO CC-13) [NCT02515734], is on-going to evaluate FOLFOXIRI plus cetuximab (cet) vs. FOLFOXIRI plus bevacizumab (bev) in terms of depth of response as primary endpoint in 360 mCRC patients (pts) with RAS wild-type tumors, PS0-1, and no previous chemotherapy. This is a head-to-head comparat...
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e14567 Background: Levels of cell-free circulating RNA (cfRNA) in cancer patients (pts) indicate tumor gene expressions and thus may provide a means, not only of evaluating response, but also for monitoring and predicting outcome to therapy. Methods: Blood was drawn every 6-8 weeks from pts undergoing various treatments (tx). CfRNA was extracted fr...
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Molecular profiling of prostate cancer with liquid biopsies, such as circulating tumor cells (CTCs) and cell-free nucleic acid analysis, yields informative yet distinct data sets. Additional insights may be gained by simultaneously interrogating multiple liquid biopsy components to construct a more comprehensive molecular disease profile. We conduc...
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Background: Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, pr...
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274 Background: Molecular profiling of prostate cancer using liquid biopsies such as CTC capture and cell-free nucleic acid analysis yield informative yet distinct datasets. Additional insights may be gained by simultaneously interrogating multiple liquid biopsy components to construct a more comprehensive molecular disease profile. We have conduct...
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380 Background: Recent studies have identified panels of immune-related genes linked to progression and survival. Expressions usually are measured using RNA from tissue samples. The aim of the present study was to utilize circulating RNA (cfRNA) isolated from hormone-naïve (HN) and castrate-resistant prostate cancer (CRPC) patients to measure gene...
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Background: In addition to traditional radiology tests, cell-free circulating tumor RNA (cfRNA) extracted from plasma of cancer patients (pts) provides a means of evaluating tumor response, but based on molecular changes in the tumor. Measuring dynamic changes in gene expression and levels of total cfRNA (per ml of plasma) in metastatic patients ha...
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11550 Background: There is an unmet need to evaluate tumor response by other means than radiology tests. Changes in gene expression, allele-fractions of mutations, PDL-1 expression and levels of cell free DNA [DNA] or RNA [RNA] in plasma might be useful for monitoring disease state and predicting outcome to anti-tumoral therapy. Methods: We measure...
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Folates have been used with cytotoxic agents for decades and today they are used in hundreds of thousands of patients annually. Folate metabolism is complex. In the treatment of cancer with 5-fluorouracil, the administration of folates mechanistically leads to the formation of [6R]-5,10-methylene-tetrahydrofolate, and the increased concentration of...
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Neoadjuvant chemotherapy (NAC) has become a standard therapy for patients with advanced breast cancer. Pathological complete response (pCR) after NAC is an important prognostic indicator, but some patients with pCR continue to experience recurrence. So new predictive and prognostic markers in addition to pCR are needed following NAC for breast canc...
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Over the past 60 years, chemotherapeutic agents that target thymidylate biosynthesis and the enzyme thymidylate synthase (TS) have remained among the most-successful drugs used in the treatment of cancer. Fluoropyrimidines, such as 5-fluorouracil and capecitabine, and antifolates, such as methotrexate and pemetrexed, induce a state of thymidylate d...
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In colorectal cancer MLH1 deficiency causes microsatellite instability, which is relevant for the patient's prognosis and treatment, and its putative heredity. Dysfunction of MLH1 is caused by sporadic gene promoter hypermethylation or by hereditary mutations as seen in Lynch Syndrome. The aim of this study was to determine in detail how DNA methyl...
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Background Cholangiocarcinoma remains to be a tumor with very few treatment choices and limited prognosis. In this study, we sought to determine the prognostic role of fms-related tyrosine kinase 1/vascular endothelial growth factor receptor 1 (FLT1/VEGFR1), heparanase (HPSE) and epidermal growth factor receptor (EGFR) gene expression in patients w...
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The aim of this study was to investigate the relevance of mRNA expression and DNA methylation of GST-PI in tumor and non-tumor lung tissue from NSCLC patients in terms of prognostic and pathogenetic value of this biomarker. Quantitative real-time PCR was used to measure mRNA expression and DNA methylation of GST-PI in paired tumor (T) and non-tumor...
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The phase III CONFIRM clinical trials demonstrated that metastatic colorectal cancer patients with elevated serum lactate dehydrogenase (LDH) had improved outcome when the vascular endothelial growth factor receptor (VEGFR) inhibitor PTK/ZK (Vatalanib) was added to FOLFOX4 chemotherapy. We investigated the hypothesis that high intratumoral expressi...
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7066 Background: In the New England Journal of Medicine, Brock et al. (2008) published a nested case-control study which tested the association between early recurrence of NSCLC after surgical resection, and TSG promoter methylation in tumor and lymph nodes detected by methylation-specific PCR (MSP). They reported that promoter methylation of the T...
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Barrett’s esophagus is a multistage polyclonal disease that is associated with the development of adenocarcinoma of the esophagus and csophagogastric junction. Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for...
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Molecular markers to predict response to 5-fluorouracil (FU)-based treatment of recurrent or metastasised colorectal cancer (mCRC) are not established. The aim of this trial was to determine the value of thymidylate synthase (TS), a key enzyme of DNA synthesis and target of 5-FU, to predict response to chemotherapy of mCRC. Tumour tissue was obtain...
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Microsatellite instability (MSI) is caused by defective mismatch repair (MMR) and is one of the very few molecular markers with proven clinical importance in colorectal cancer with respect to heredity, prognosis, and treatment effect. The gene expression of the MMR gene MSH2 may be a quantitative marker for the level of MMR and a potential molecula...
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Oropharyngeal squamous cell carcinomas (OSCC) constitute about 5% of all cancers in the western world and the incidence and mortality rates of this tumor have shown little improvement over the last 30 years. Molecular targeted therapy, a promising strategy for the treatment of OSCC and other cancers, requires the understanding of specific molecular...
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To validate established cutoff levels of thymidylate synthase (TS) and excision repair cross-complementing (ERCC-1) intratumoral mRNA expressions in tumor samples from metastatic colorectal cancer (mCRC) patients treated with PTK787/ZK222584 (PTK/ZK). From 122 samples of patients with mCRC enrolled in CONFIRM-1 (Colorectal Oral Novel Therapy for th...
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7056 Background: Differential expression of DNA repair proteins plays a role in drug sensitivity. In lung cancer, low ERCC1 expression is associated with platinum responsiveness. Additional analyses have identified associations between ERCC1 mRNA expression levels and histology and gender (Gandara ASCO 2010). BRCA1 has emerged as another important...
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Phase II trials in locally advanced rectal cancer have shown that cetuximab-based neoadjuvant radiochemotherapy is feasible but without an improvement in complete pathologic response rates. Our goal was to identify patients who would benefit from cetuximab-based neoadjuvant chemoradiation measuring gene expression levels of proteins involved in tum...
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Background: Pathologic complete response (pCR) following neoadjuvant therapy (NCT) may predict for improved survival. Hence, more effective and individualized/targeted NCT regimens in conjunction with molecular markers that predict for both response and/or resistance are needed. Materials and Methods: 119 evaluable pts (121 enrolled) with stages II...
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226 Background: Cholangiocellular carcinoma (CCC) remains to be a tumor with very few treatment choices and limited prognosis. In this study, we sought to determine the prognostic role of VEGF receptor 1 (VEGFR1), heparanase (HPSE) and EGF receptor (EGFR) gene expression in patients with resected CCC. Methods: 47 formallin-fixed paraffin embedded F...
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Androgens stimulate the expression of vascular endothelial growth factor (VEGF) through activation of hypoxia inducible factor (HIF). These genes play a major role in cancer angiogenesis. This study assesses the relationship among expression levels for the androgen receptor (AR), HIF1a, VEGF-A, and VEGF-C genes in human prostate cancer tissue and t...
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The effect of the apoptosis related gene Bcl-2 in the pathogenesis in NSCLC remains poorly investigated. Hence the aim of this study was to explore the potential role of Bcl-2 mRNA expression as a prognostic biomarker in patients with curatively resected NSCLC. 91 tumor and matching normal tissue samples from patients with NSCLC were analyzed using...
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Patients with non-small cell lung cancer (NSCLC) with cancers harboring activating mutations in the epidermal growth factor receptor (EGFR) show improved efficacy from EGFR tyrosine kinase inhibitors. Some clinical studies also suggest enhanced efficacy of platinum-based chemotherapy in patients with EGFR-mutant cancers. We investigated the relatio...
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Thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) are key enzymes in the 5-fluorouracil (5-FU) pathway. The aim of this study was to investigate the mRNA expression of TS, TP, and DPD in tumor and nontumor lung tissue of patients with NSCLC and to determine the potential of these genes as molecular b...
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PURPOSE: The role of adjuvant chemotherapy in patients with locally advanced bladder cancer still remains to be defined. We hypothesized that assessing the gene expression of the chemotherapy response modifiers multidrug resistance gene 1 (MDR1) and excision repair crosscomplementing 1 (ERCC1) may help identify the group of patients benefiting from...
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The role of adjuvant chemotherapy in patients with locally advanced bladder cancer still remains to be defined. We hypothesized that assessing the gene expression of the chemotherapy response modifiers multidrug resistance gene 1 (MDR1) and excision repair cross-complementing 1 (ERCC1) may help identify the group of patients benefiting from cisplat...
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10535 Background: The echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (EML4-ALK) fusion gene can be detected in subsets of NSCLC, especially never-smoking patients with adenocarcinoma, and appears to be mutually exclusive of EGFR mutation. PF-1066, a potent and selective c-MET/ALK inhibitor, yields high response rates in...
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10522 Background: Targeted treatment strategies have been developed to improve survival of patients (pts) with metastatic colorectal cancer. Vatalanib (PTK787/ZK 222584) is an oral angiogenesis inhibitor and was combined with FOLFOX in first- (CONFIRM 1) and in second line (CONFIRM 2) but did not significantly improve progression-free survival or o...
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The effect of ornithine decarboxylase (ODC) on the pathogenesis of non-small-cell lung cancer (NSCLC) remains poorly investigated. Hence, the aim of this study was to explore the potential role of ODC mRNA expression as a prognostic biomarker in patients with curatively resected NSCLC. A total of 91 tumor and matching nontumorous lung tissue sample...
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Finding markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens in soft tissue sarcomas is necessary. In this study, we investigated the prognostic values of hypoxia-inducible factor 1a (HIF1a), heparin-binding epidermal growth factor-like gro...
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High expression levels of EGFR mRNA are reported to be associated with a higher response probability in epidermal growth factor receptor (EGFR) targeted drugs. Our aim was to determine how EGFR gene expression levels in primary colorectal cancer (CRC) were related to those in liver metastases. 31 pairs of primary CRC and corresponding liver metasta...
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Thymidylate synthase (TS) is known to have a unique 28 bp tandemly repeated sequence in the promoter region, and the majorities of subjects have a heterozygous double repeat/triple repeat genotype in their non-cancerous tissue. Loss of heterozygosity (LOH) at the TS locus is known to occur in cancer patients, but there is no evidence that it is pre...
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5026 Background: The human MDR1 gene encodes an integral membrane protein, P glycoprotein (Pgp), whose function is the energy dependent export of substances from the inside of cells, and from membranes, to the outside. MDR1 mRNA levels have been shown to influence metabolism of cancer drugs. We tested whether MDR1 gene expression is associated with...
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Several new drugs that are targeted towards various angiogenic factors have shown considerable potential for controlling tumor proliferation and metastases. Expression levels of the targeted genes in primary tumors and metastases should be understood to maximize the use of such drugs. The present study aimed to clarify associations between mRNA lev...
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The p16 gene encodes a 16-kDa cyclin kinase inhibitor, and the p14ARF gene a 14-kDa protein, which acts as a cell cycle regulator or tumor suppressor in human cancer cells. Both genes are mapped on chromosome 9p21. Previous studies have suggested that the p16 gene has important roles in head and neck squamous cell carcinoma. To clarify carcinogenes...
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Neuroendocrine (NE) cells are present in both normal prostate and prostate cancer. In addition, NE differentiation can be induced by various factors, such as IL-6, in vitro and in vivo. However, the mechanism of this differentiation and the role of NE cells in prostate cancer are not well understood. In this study, we evaluated the gene expression...
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5-fluorouracil (5-FU) and oxaliplatin play important roles in chemotherapy for patients with colorectal cancer. The expression levels of thymidylate synthase (TS) and excision repair cross-complementing factor 1 (ERCC1) have been reported to be prognostic markers for patients with 5-FU/oxaliplatin chemotherapy. The aim of this study was to clarify...
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It has been reported that the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT) may predict the clinical efficacy of 5-fluorouracil (5-FU)-based therapy in cancer patients. We investigated the differences in the mRNA and protein expression of these enzymes in various tumor ti...
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Background. To further improve the screening, diagnosis, and therapy of patients with nonsmall cell lung cancer (NSCLC) additional diagnostic tools are urgently needed. Gene expression of Cyclooxygenase-2 (COX-2) has been linked to prognosis in patients with NSCLC. The role of the COX-2 926G>C Single Nucleotide Polymorphism (SNP) in patients with N...
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Over-expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in tumor tissue is associated with insensitivity to 5-fluorouracil (5-FU). Over-expression of ERCC1 correlates with insensitivity to oxaliplatin (OX) therapy, while high thymidine phosphorylase (TP) levels predict for increased sensitivity to capecitabine (Xel)....
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Patients with high-risk primary breast cancer remain at high risk for relapse. More precise prognostic and predictive tools are needed to improve treatment of such patients. Formalin-fixed, paraffin-embedded tumors from 239 high-risk breast cancer patients were examined for expression of human epidermal growth factor receptor 2 (HER2), epidermal gr...
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Beta-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) have been frequently considered as constitutive house keeping genes for RT-PCR and used to normalize changes in specific gene expressions. However, these expressions have been shown to be affected by the sample type and experimental conditions. We investigated which housekeeping gene i...
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Pancreatic cancer still has one of the worst prognoses of all cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. Especially heparanase (HPSE) has recently been discus...