Caris Life Sciences®
Posters, Abstracts & Newsletters
With every passing day, new discoveries are made that lend support to the increasing role of biomarker analysis and molecular profiling in cancer diagnosis and treatment. The following studies related to biomarkers and molecular profiling were presented, authored and/or co-authored by our tumor profiling experts.
Read about the clinical utility of molecular profiling as published in the Journal of Clinical Oncology.
Posters
2013 Gastrointestinal Cancers Symposium
For patients (pts) with advanced PBC who are able to pursue additional therapy, treatment selection is often empiric and clinical benefits are usually modest. Our goal was to study clinical outcomes of MP-guided treatment in advanced PBC. This retrospective analysis included pts with advanced PBC whose tissue samples underwent MP (IHC, microarray [MA], and sequencing analyses) using Target Now (Caris Life Sciences, Irving, TX). These pts received ≥1 lines of therapy for advanced PBC before their treatment was guided by MP.
2012 22nd Biennial European Association for Cancer Research (EACR) Congress
Ewing Sarcoma (ES)/PNET and Desmoplastic Small Round Cell Tumor (DSRCT) are sarcomas with distinct chromosomal translocations involving the EWS gene (predominately EWS-FLI1 and EWS-WT1; respectively). Their diagnosis and treatment have been difficult due to the rarity, diverse clinical presentation, overlapping histologic features and genetic complexity. Identification of therapeutically targetable genes or pathways in distinct tumor group and individual patient might provide more effective therapeutic strategies.
2012 American Society of Clinical Oncologists (ASCO) Annual Meeting
Examining actionable targets in patients’ pancreatic cancers (a)reiterates the commonality and importance of KRAS mutations in this disease (needs renewed targeting effort); (b)suggests that TOPO2 inhibitors (particularly if transport into tumor can be improved) should be examined in this disease; (c)suggests other pathways to target including DNA repair, epigenetic, Src and inflammation; (d) suggests protein turnover, amino acid targets and folate receptor 2 as fresh areas to explore against the disease. Supported in part by a Stand Up To Cancer Dream Team Award and by Caris Life Sciences.
The taxanes are an important class of agents for the treatment of a broad range of malignancies including breast cancer. They improve survival in patients with early stage and metastatic breast cancer. Transducin-like enhancer of split 3 (TLE3) is a transcriptional repressor which influences growth and microtubule stability and its expression has been implicated in response to taxane therapy in breast cancer. We investigated the tumor expression of TLE3 in breast cancer patients, including a large cohort of the triple negative subtype.
Molecular Profiling of Uveal Melanoma Patients
Although uveal melanoma represents only 5% of all melanomas, it is the most common primary intraocular malignancy of the adult eye. Approximately 50% of patients will develop metastases which are resistant to medical interventions. There is a great need for improved therapy as the prognosis is poor for advanced-stage disease. Our study was undertaken to investigate the presence of novel therapeutic targets.
Differences in Biomarker Expression in HNSCC According to p53 Status
Patients with p53 wildtype head and neck squamous cell carcinoma (HNSCC) tend to be HPV-positive, which associates with better prognosis. The purpose of this study was to explore biomarker expression profiles for insight into molecular differences in HNSCC patients based on p53 status.
2012 American Society of Clinical Oncologists (ASCO) Annual Meeting Online-Only Abstracts
The Caris registry: Building a biomarker-focused database to advance patient care.
Differential expression of biomarkers in gastrointestinal versus pulmonary carcinoid tumors.
Theranostic profiling of Ewing sarcoma (ES) and desmoplastic small round cell tumors (DSRCT).
2012 Multidisciplinary Head and Neck Cancer Symposium
Biomarker Expression in Head and Neck Squamous Cell Carcinoma – Implications for Therapy
Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with an unpredictable prognosis. Failure of first-line treatment is common, thus additional therapeutic options are in great need. The purpose of this study was to explore biomarker expression profiles of HNSCC for therapeutic strategies that are not commonly pursued.
35th Annual San Antonio Breast Cancer Symposium (SABCS)
PTPN12 Gene Expression Signature in Triple Negative Breast Cancer Cohort
PTPN12 tyrosine phosphatase may play a role in tumor development/progression in triple negative breast cancer patients (TNP). The effects of PTPN12 appear to be mediated through several tyrosine kinase receptors including EGFR, HER2, and PDGFR-beta. We investigated the variability associated with PTPN12 transcript in the microarray gene expression data obtained from 105 TNP as determined by IHC for ER and PR and IHC and FISH for HER2 during our clinical molecular profiling on solid tumors. The mRNA levels of PTPN12 in our cohort was highly variable suggesting a complex genetic regulation of PTPN12 transcription in TNP patients. The highly variable nature of PTPN12 mRNA levels lead us to perform a correlation-based analysis of the transcriptome in TNP samples to gain insight into pathways and cellular processes associated with PTPN12 variation.
All together our results provide support for the involvement of PTPN12 in cancer development and highlights a promising therapeutic target for TNP patients.
AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics
Despite the widespread use of prostate specific antigen screening for early detection, prostate cancer remains the second leading cause of cancer related death among men in the US. Metastatic, hormone refractory prostate cancer (HRPCa) is the end stage, lethal form of the disease. Defining the molecular mechanisms underlying the transition of an androgen responsive prostate cancer represents an important clinical problem. Currently, no effective therapies exist for end stage, hormone refractory disease. In this study, we investigated the differentially expressed genes in primary prostate tumor vs. hormone refractory prostate tumor in order to identify potentially important therapeutic targets.
59th Annual Scientific Meeting of the American Society of Cytopathology (ASC)
Malignant Peritoneal and Pleural Fluid Samples Are Adequate for Molecular Profiling
The diagnosis of a malignant effusion in the serosal cavities is a frequent event in the clinical setting of cancer. Metastatic cancer cells may have unique characteristics that give them the ability to migrate from the primary tumor. Since cancer patients often experience critical conditions, the analysis of the malignant fluid might be the only tissue sample available for these patients. With the focus on targeted therapies, evaluation of different sample types for molecular studies is even more important
Caris Target Now is a proprietary evidence-based molecular profiling system for solid tumors which provides specific and individualized molecular profiles for guidance of therapy in advanced stages and metastatic malignancies. It associates therapeutic agents with potential benefit or potential lack of benefit and may reveal treatments not previously considered.
12th Annual International Congress of Human Genetics
Clinical Laboratory Experience of Gene Expression Profiling of 2,384 solid tumors
Optimizing therapeutic selections for cancer patients using the molecular profile of their tumor is an unmet need. Currently, many providers use results of tumor profiling by platforms including IHC, FISH and mutational analyses to identify potential cancer treatments. Gene expression profiling with microarrays also has the potential to help classify solid tumor subtypes and assist with therapy selections based on the under or over-expression of particular transcripts.
Breast Cancer Symposium 2011
Molecular Profiling of Metastatic Breast Cancer in Body Cavity Fluids
The diagnosis of malignant effusion signifies disease progression and is associated with a worse prognosis regardless of tumor origin. The cancer cells in fluids have unique genotypic and phenotypic characteristics that are uniquely different from the primary tumor. Therapeutic guidance should be based on the evaluation of tumor cells in effusions. This study reports the feasibility of molecular profiling for breast cancer metastasis in pleural and peritoneal fluids.
Frequency distribution of SPARC in triple-negative breast cancer patients
Background: SPARC (secreted protein acid rich in cysteine) belongs to a group of extracellular matrix proteins and promotes adhesion of cells to the matrix. As such, expression of this protein plays an important role in tumor development in breast cancer and has a significant bearing on patient prognosis and long term survival. It is also known to predict response to nab-paclitaxel in certain tumor types including breast cancer. In 2005, the FDA approved a solvent free formulation of paclitaxel for the treatment of metastatic breast cancer that utilizes albumin bound (nab) technology (Abraxane; nab-paclitaxel). Clinical studies have shown that nab-paclitaxel is significantly more effective than paclitaxel. Our study was designed to evaluate the frequency distribution of SPARC among breast cancer patients with a special emphasis on triple negative patients in which identification of a novel therapeutic target is warranted.
American Association for Cancer Research (AACR) 2011
The importance of steroid hormone receptors to the biology of breast cancer was recognized over 40 years ago. New insights into hormone receptor biology and the increasing array of proteins that can modify their function have already translated into better therapies for breast cancer. The responsiveness of a tumor to hormone therapy is an important parameter in cancer management. Besides breast cancer, other cancers also express steroid hormone receptors. Hence, the purpose of this study was to capture the relative distribution of hormone receptors in all types of cancer including breast cancer.
Correlation of HER2 expression by IHC, DNA microarray, and FISH in breast cancer
HER2 overexpression occurs in approximately 15-20% of patients with breast cancer and is associated with aggressive disease and decreased survival. HER2 status is predictive of response to trastuzumab and lapatinib. Given the importance of HER2 positive disease, accurate evaluation of HER2 status is essential. The aim of this study is to provide insights into the relationship between HER2 expression by immunohistochemistry, DNA microarray and FISH in a large cohort of 1,032 breast cancers. HER2 protein expression were determined using antibody clones (4B5) and interpreted per ASCO/CAP scoring criteria. Samples scored as equivocal (≥2+;> 10% to <+3+; ≤30%) were required to undergo further assessment with FISH HER2 testing (Pathvysion). All samples were tested for HER2 by DNA microarray provided there was sufficient quantity of RNA in all tumor samples.
American Association for Cancer Research (AACR) 2009
KRAS and BRAF Mutation Spectrum In 1,035 FFPE Tumor Samples Submitted For Clinical Testing
Activating mutations both the KRAS and BRAF in genes are associated with poor prognosis and nonresponse to anti-EGFR therapies in patients with advanced cancers. Clinical guidelines have recommended that KRAS mutational status be determined in all patients with metastatic colorectal cancer that are being considered for anti-EGFR therapies. In this study, a pathologist reviewed an H&E slide of each tumor sample and determined the percent tumor nuclei and percent necrosis.
Newsletters
Molecular Intelligence Newsletter – Targeting: Melanoma
- Welcome Letter from guest editor, Dr. Omid Hamid - Chief, Translational Research and Immunotherapy & Director, Melanoma Therapeutics at the The Angeles Clinic and Research Institute
- Highlights on Melanoma research, including:
- Biomarker News
- BRAF
- MEK
- mTOR
- PIK3CA
- Therapy Updates
- vemurafenib
- pan-RAF inhibitor
- MEK inhibitor
- Biomarker News
Caris Target Now News – Fourth Quarter 2010
- Welcome Colleague
- Bisgrove Study Suggests Therapy Options Based on Caris Target Now Molecular Tumor Profiling Prolong Progression-Free Survival in Some Cancer Patients
- Significant Expansion to Panel of Breast Cancer Biomarkers Analyzed by Caris Target Now Includes 14 New Biomarkers
- Hot Biomarker – TLE3
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