Abstract A37: Cholesterol biosynthesis pathway as a novel mechanism of resistance identified in ER+ long-term estrogen deprived cells
Over 80% of breast cancers (BC) at primary diagnosis express the estrogen receptor (ER+). Therapies targeting the estrogenic stimulation of tumor growth reduce mortality from ER+ BC but resistance remains a major clinical problem. Data from large studies such as TCGA indicate that other than a small number of high frequency mutations such as TP53, PIK3CA and GATA3 that have little association with endocrine resistance, primary ER+ BC shows very low frequency of individual mutations making targeting difficult. In contrast, expression profiling of primary ER+ BC samples have identified several promising signatures/networks f...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Simigdala, N., Gao, Q., Pancholi, S., Zvelebil, M., Ribas, R., Dowsett, M., Martin, L.-A. Tags: Luminal Breast Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B36: Inhibition of the autocrine IL-6-JAK2-STAT3-Calprotectin axis as targeted therapy for HR-/HER2+ breast cancers
Although, HER2+ tumors are commonly considered as a single entity, there is increasing evidence indicating that important intrinsic differences associated to hormone receptor status (HR) exist. Each of the two groups, HR+ and HR-, represent about 1/2 of all HER2+ breast cancers.Compared to HR+/HER2+, HR-/HER2+ tumors present worst histopathological characteristics. HR+/HER2+ tumors preferentially recur in bone while there is a strong trend for more visceral metastases in the HR-/HER2+ cancers. Moreover, despite a higher rate of pathologic complete responses (pCR) to neoadjuvant chemotherapy HR-/HER2+ patients still have an...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Yu, J., Califano, A., silva, j. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A36: Protein expression analysis of intratumor heterogeneity in a luminal-like breast cancer xenograft
Estrogen receptor is a key driver in breast cancer and is expressed in about 75% of breast tumors. ER positive tumors are susceptible to endocrine therapies; however, the major obstacle for curative treatment is recurrence due to resistance to anti-estrogens. Endocrine therapies may induce a selective pressure promoting growth of estrogen independent cell subclones. Our aim was to reveal molecular changes occurring in tumors in response to anti-estrogen treatment, and to identify subpopulations of cells able to withstand anti-estrogen treatment.A luminal-like estrogen-dependent orthotopically growing xenograft model was tr...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Skrbo, N., Kirik, U., Kristian, A., Cifani, P., Antberg, L., Moestue, S. A., Engebraaten, O., Maelandsmo, G. M., Andersen, K., James, P., Sorlie, T. Tags: Luminal Breast Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B35: Concurrent use of alisertib and vaccinia virus demonstrate increased in vitro efficacy against breast cancer models with elevated numbers of cancer stem-like cells
Background: Accumulating evidence indicates that breast cancer progression, resistance to therapies and development of metastasis are driven by cancer cells with stem cell-like characteristics. The increased numbers of cancer stem-like cells (CSCs) have been reported in triple negative breast cancers (TNBCs). Therefore, novel methods for targeting CSC population are needed. Aurora-A kinase (AURKA) has been shown to play a key role in acquisition of stem cell-like properties by breast cancer cells. Furthermore, the CSCs have been demonstrated to have increased sensitivity to AURKA specific inhibitor, MLN8237 (Alisertib). Ou...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Gil, M., Komorowski, M., Kozbor, D., Opyrchal, M. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A35: WNT4 signaling mediates endocrine response and resistance in invasive lobular carcinoma cells
Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer, affecting ~30,000 U.S. women annually. Over 90% of ILC are estrogen receptor (ER)-positive, however, endocrine therapy may have poorer efficacy in a subset of ILC patients compared to invasive ductal carcinoma (IDC) patients. Based on these observations, we assessed genome-wide ER-mediated gene expression and ER genomic binding in ILC cell lines MDA MB 134VI (MM134) and SUM44PE (44PE), to identify novel mediators of ER signaling and putative therapeutic targets specifically in ILC.Among ILC-specific estrogen-regulated genes, the most strongly indu...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Sikora, M. J., Bahreini, A., Alexander, C. M., Oesterreich, S. Tags: Luminal Breast Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B34: PIM kinase as a novel therapeutic target for triple-negative breast cancer
The greatest clinical challenge in treating breast cancer occurs in those patients whose tumors lack expression of the estrogen and progesterone receptors and that of the HER2 oncoprotein. No targeted therapeutic strategies currently exist against this aggressive type of "triple negative" breast cancer (TNBC) due to lack of validated targets. We previously found that MYC mRNA, protein, and its signaling were disproportionally elevated in TN compared to receptor positive (RP) breast cancer. We sought to take advantage of the unique molecular feature found in this tumor type to identify potent and effective treatme...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Horiuchi, D., Zhou, A. Y., Corella, A. N., Yau, C., Balakrishnan, S., Kessenbrock, K., Lawson, D. A., Camarda, R., Anderton, B. N., Bazarov, A. V., Eyob, H., Rohrberg, J., Yaswen, P., McManus, M. T., Rugo, H. S., Werb, Z., Goga, A. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A34: BRCA1 and BRCA2 mutation spectrum across 5, 509 high-risk individuals identifies pathogenic variants associated with ethnicity, age of diagnosis, and type of cancer
Hereditary Breast and Ovarian Cancer Sydrome (HBOC) accounts for approximately 5-10% of breast and ovarian cancer cases and germline mutations of the BRCA1 and BRCA2 genes confer substantially increased risk. However, the risk of developing cancer, the type of cancer and the associated age at diagnosis vary depending on the type of mutation carried and the individual's ethnic background and gender. Screening of BRCA1 and BRCA2 mutations was conducted on 5, 512 high-risk individuals with a prior probability of carrying a pathogenic mutation (>10% chance) from the Advanced Molecular Diagnostics Laboratory (AMDL) (Mount Si...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Girgis, A. H., Wang, M., Fine, A., Zakoor, K.-R., Khalouei, S., Charames, G., Lerner-Ellis, J. Tags: Genomics - Sporadic and Hereditary: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A33: Expression of BRCA2 and Mir-21 in sporadic and BRCA2 mutated breast cancer in Iceland
The BRCA2 protein plays an important role in the repair of double-stranded DNA breaks (DSBs) by homologous recombination. An inherited founder mutation in the BRCA2 gene accounts for 6-7 % of all breast cancers in Iceland. Breast cancer in BRCA2 mutation carriers is associated with poor long-term prognosis. It has been reported that> 20% of sporadic breast cancers display a BRCA-like phenotype (BRCA‘ness), suggesting a defect in the DSB repair pathway. Little is known about the role of miRNAs in BRCA2 related breast cancer. Analysis of array CGH data from BRCA2 breast tumors shows that the mir-21 locus on chromoso...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Reyisdottir, S. T., Reynisdottir, S. T., Stefansson, O. A., Bödvarsdottir, S. K., Palsson, A., Eyfjörd, J. E. Tags: Genomics - Sporadic and Hereditary: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B32: Microenvironmental distribution of trastuzumab in metastases and xenograft models is highly heterogeneous and decreases sharply when administered in combination with bevacizumab
Despite significant success, the response of Her2+ patients to trastuzumab (TzMAb, Herceptin ®) is varied, with many still experiencing tumor progression. We have used 3D tissue, tumor xenograft and metastatic models to examine the microregional distribution of TzMAb when administered alone or in combination with bevacizumab (BvMAb).Methods: Her2 positive (Her2+) SKOV-3 ovarian and MDA361, JIMT-1, BT474 mammary cancer cells were grown as 3D tissue discs, spheroids and as xenografts. Her2 expression was ranked as SKOV3> BT474> JIMT-1> MDA361. Variable concentrations (25-100 µg/mL for in vitro; 2.5-10 mg/k...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Baker, J. H. E., Kyle, A. H., Cran, J., Patrick, H., Gandolfo, M.-J., Minchinton, A. I. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A32: MCL1 gene amplification in breast cancer is associated with TNBC status and can respond to a sorafenib/vorinostat regimen
Background: MCL1 encodes the induced myeloid leukemia cell differentiation protein Mcl-1, a member of the BCL-2 family which functions to inhibit apoptosis. Mcl-1 over-expression has been associated with high tumor grade and adverse prognosis in triple negative breast cancer (TNBC) but therapies specifically leading to inhibition of MCL-1 have not been identified.Methods: Comprehensive genomic profiling (CGP) using hybridization capture of 3,769 exons from 315 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to ≥50ng of DNA extracted from 2,824 consecutive BC and sequenced to hig...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Ross, J., Wang, K., Johnson, A., Watson, J., Hatzis, C., Pusztai, L., Chmielecki, J., Yelensky, R., Lipson, D., Elvin, J., Vergilio, J., Suh, J., Miller, V., Dicke, K., Stephens, P., Ali, S. Tags: Genomics - Sporadic and Hereditary: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A31: Integrative differential allelic expression analysis efficiently reveals the biology underlying risk to breast cancer
Breast cancer is the most common cancer affecting women in the developed world. However, the current knowledge of breast cancer genetic risk cannot explain as much as two-thirds of cases. While successful, GWAS have not: (1) contributed to explain the genetic causality of risk; (2) provided an indication of the biological mechanisms involved.Based on our previous results demonstrating that cis-regulatory variation is involved in breast cancer risk, we have performed whole-genome differential allelic expression (DAE) analysis of sixty-four normal breast tissue samples. We integrated this genome-wide DAE map with published b...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Xavier, J., Russell, R., Almeida, B. P., Rosli, N., Rocha, C., Samarajiwa, S., Chin, S.-F., Caldas, C., Ponder, B. A., Maia, A.-T. Tags: Genomics - Sporadic and Hereditary: Poster Presentations - Proffered Abstracts Source Type: research

Abstract IA30: Insights into metabolome of breast cancer
Metabolomics describes the science of quantifying the levels of metabolites (e.g., small molecules
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Sreekumar, A. Tags: New Omics in Breast Cancer: Oral Presentations - Invited Abstracts Source Type: research

Abstract B30: Ex vivo culture of breast cancer patient-derived xenografts in modified 3-D hyaluronan hydrogels
The high attrition rate of potential anti-cancer drugs entering clinical trials indicates the need for more predictive pre-clinical model systems. Standard compound screening is high-throughput and relatively inexpensive, but conducted with non-representative cells in a non-physiological environment. Three-dimensional (3D) culture systems provide cells a more physiological microenvironment including relevant extracellular matrix (ECM) cues and cell-cell interactions. Patient-derived xenograft (PDX) culture preserves tumor heterogeneity while mitigating harsh selective pressures induced by traditional 2D culture methods. Ho...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Sablatura, L. K., Kavuri, M., Richards, P., Harrington, D. A., Ellis, M. J., Farach-Carson, M. C. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A30: RATHER: High-resolution molecular profiling of invasive lobular breast cancers
Conclusion: We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization will help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.Citation Format: Suet-Feung Chin, Magali Michault, Ian Majewski, Tesa M. Severson, Tycho Bismeijer, Leanne De Korning, Justine Peeters, Phillip Schouten, Oscar M. Rueda, Astrid Bosma, Finbarr Tarrant, Yue Fan, BeiLei He, Bernard Pereira, Helen A. Bardwell, Elena Provenzano, Darran P. O'Connor, Sabine Linn, Thierry Dubois, Iris Simon, William Gall...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Chin, S.-F., Michault, M., Majewski, I., Severson, T. M., Bismeijer, T., Korning, L. D., Peeters, J., Schouten, P., Rueda, O. M., Bosma, A., Tarrant, F., Fan, Y., He, B., Pereira, B., Bardwell, H. A., Provenzano, E., O'Connor, D. P., Linn, S., Dubois, T., Tags: Genomics - Sporadic and Hereditary: Poster Presentations - Proffered Abstracts Source Type: research

Abstract IA29: Proteogenomic and phosphoproteomic analysis of breast cancer
The genetic landscape of human breast cancer has been well defined in The Cancer Genome Atlas (TCGA) project. Mass spectrometry (MS)-based global proteome and phosphoproteome analyses provide a complementary, orthogonal approach to genomic studies to further improve the molecular taxonomy and biological understanding of breast cancer. We analyzed human breast cancer samples that had previously undergone comprehensive genomic and reversed phase protein array (RPPA) characterization by TCGA. Tumor samples were analyzed by global shotgun proteomics and phosphoproteomics at an unprecedented coverage of>11,000 quantified pro...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Mertins, P., Mani, D., Ruggles, K., Gillette, M., Clauser, K., Wang, P., Wang, X., Qiao, J., Cao, S., Petralia, F., Mundt, F., Tu, Z., Lei, J., Gatza, M., Wilkerson, M., Perou, C., Yellapantula, V., Huang, K.-l., Lin, C., McLellan, M., Yan, P., Davies, S. Tags: New Omics in Breast Cancer: Oral Presentations - Invited Abstracts Source Type: research

Abstract B29: Anti-breast cancer effects of the Vav/Rac inhibitor Ehop-016 in the tumor microenvironment
This study was supported by National Institute on Minority Health and Health Disparities of the National Institutes of Health (NIMHHD/NIH) U54MD008149 and the Puerto Rico Science and Technology Trust to SD; Title V PPOHA P031M10505 and Title V Cooperative P031S130068 from U.S. Department of Education, and RCMI 8G12MD007583 to UCC; and UPR RCM NIH/NIMHHD grants 5U54CA096297 andR25GM061838 to THB.Citation Format: Linette Castillo-Pichardo, Cristina Del Valle, Jessica Morales, Valance Washington, Krizia Rohena-Rivera, Magaly Martinez, Luis Cubano, Suranganie Dharmawardhane. Anti-breast cancer effects of the Vav/Rac inhibitor ...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Castillo-Pichardo, L., Valle, C. D., Morales, J., Washington, V., Rohena-Rivera, K., Martinez, M., Cubano, L., Dharmawardhane, S. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A29: Detection of ultra-rare mutations during breast stem cell tumor progression by Duplex Sequencing
Most studies have mainly investigated clonal mutations due to the high background error frequencies of conventional next generation sequencing (NGS) methods. We have established a new method termed Duplex Sequencing (DS) that detects mutations with unprecedented accuracy and enables us to detect sub-clonal and rare mutations as well as clonal mutations. Using DS, we present our first genome-wide analysis of mitochondrial (mt) DNA mutations during the transformation of human normal breast stem cells to tumorigenic cells. We used a model system to dissect sequential steps in the progression of normal stem cells to tumorigeni...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Ahn, E. H., Hirohata, K., Lee, S. H., Kim, J. Y., Kohrn, B. F., Fox, E. J., Chang, C.-C., Loeb, L. A. Tags: Genomics - Sporadic and Hereditary: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B28: Activating mutations in PIK3CB confer resistance to PI3K inhibition in PTEN-deficient breast cancer and define a novel oncogenic role for p110{beta}
Activation of the phosphoinositide 3-kinase (PI3K) pathway occurs commonly in breast cancers via mechanisms that include loss of function of the tumor suppressor phosphatase and tensin homolog (PTEN). Experience with other successful targeted agents suggests that clinical resistance to PI3K inhibitors is likely to arise and may reduce the durability of clinical benefit. Here, we sought to understand mechanisms underlying resistance to PI3K inhibition in PTEN deficient breast cancers. PTEN null breast cancer cell lines were selected for resistance to a pan-PI3K inhibitor, GDC-0941. Comprehensive molecular and cellular profi...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Nakanishi, Y., Walter, K. M., Spoerke, J. M., O'Brien, C., Huw, L. Y., Hampton, G. M., Lackner, M. R. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A28: Evaluation of CDK12 protein expression as a novel biomarker for PARP1/2 inhibitor sensitivity in breast cancer
The CycK/CDK12 complex is known to protect normal cells from genomic instability by regulating the DNA damage response (DDR) and has been postulated as a tumor suppressor gene in high-grade serous ovarian cancer. We have previously shown that in breast cancer, CDK12 is recurrently targeted by both DNA rearrangements (13% of HER2-amplified breast cancers) and recurrent point mutations (2.6% of unselected breast cancers). Furthermore, we have shown that loss of CDK12 confers sensitivity to PARP1/2 inhibitors, and therefore may constitute a biomarker of response. The aims of this study were i) to determine the frequency of CD...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Naidoo, K., Wai, P., Maguire, S., Daley, F., Yuan, Y., Rakha, E. A., Ellis, I. O., Lord, C. J., Green, A. R., Natrajan, R. C. Tags: Genomics - Sporadic and Hereditary: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B27: Targeting of phosphatidylserine by monoclonal antibody ch1N11 enhances the antitumor activity of immune checkpoint inhibitor PD-1/PD-L1 therapy in orthotopic murine breast cancer models
Conclusions: These results suggest that the combination of PS targeting antibodies in conjunction with checkpoint inhibitors has the potential to block tumor immunosuppression in breast cancer and promote a durable antitumor immune response.Citation Format: Michael J. Gray, Jian Gong, Van Nguyen, Michaela Schuler-Hatch, Chris Hughes, Jeff Hutchins, Bruce Freimark. Targeting of phosphatidylserine by monoclonal antibody ch1N11 enhances the antitumor activity of immune checkpoint inhibitor PD-1/PD-L1 therapy in orthotopic murine breast cancer models. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Br...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Gray, M. J., Gong, J., Nguyen, V., Schuler-Hatch, M., Hughes, C., Hutchins, J., Freimark, B. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A27: The genomic profile of BRCA1-associated estrogen-receptor positive breast cancer does not resemble BRCA1-associated triple negative cancers, but is more similar to BRCA2-associated breast cancer
Conclusion: The majority of BRCA1-associated ER+ tumors did not show a BRCA1-like genomic profile, even though LOH analysis indicated that loss of the wildtype BRCA1 allele was a frequent event. Therefore, it is likely that the complete loss of the BRCA1 gene plays a crucial role in tumorgenesis in this group of breast tumors. Remarkably, a BRCA2-like genomic profile was observed in the majority of ER+ BRCA1 associated tumors in this series. A clinical consequence of our findings is that ER+ BRCA1-associated breast tumors are probably highly sensitive to PARP inhibitors, similar to TN BRCA1-associated breast cancers. Howev...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Lips, E. H., Debipersad, R., Scheerman, E., Mulder, L., Kolk, L. E. v. d., Wesseling, J., Hogervorst, F. B. L., Nederlof, P. M. Tags: Genomics - Sporadic and Hereditary: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B26: Identification of genes that predict response to paclitaxel in breast cancer using an in vivo genome-wide knockdown screen
Treatment decisions for breast cancer are based upon stage, tumor grade and hormone receptor status, and can include surgical resection, hormone receptor antagonists, radiation, and chemotherapy (e.g. paclitaxel). Breast cancer treatment success depends upon avoidance of chemotherapy resistance (i.e. achieving complete response) and prevention of both over- and under-treatment. Increased understanding of the genes which cause resistance and sensitivity to currently used drugs would lead to development of more effective therapeutic strategies that are specifically tailored to patient groups based on molecular profiling of t...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Sultan, M., Huynh, T. T., Thomas, M. L., Coyle, K. M., Giacomantonio, C. A., Marcato, P. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A26: Telomere length in normal and tumor breast tissue from BRCA2 mutation carriers and sporadic breast cancer cases
Germline mutations in the BRCA genes are associated with highly increased risk of breast and ovarian cancers and to a lesser extent to prostate and pancreatic cancers. Great number of mutations with variable impact on cancer risk and progression are known in these genes worldwide. A single founder mutation has been detected in each of the BRCA genes in the Icelandic population, making it feasible to study the influence of a single mutation at a population level. The BRCA2999del5 mutation is more frequent and can be found in approximately 6-7% of female breast cancer patients and 40% of male breast cancer patients in Icelan...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Thorvaldsdottir, B., Cimini, B. A., Diolaiti, M. E., Aradottir, M., Olafsdottir, K., Jonasson, J. G., Blackburn, E. H., Eyfjörd, J. E. Tags: Genomics - Sporadic and Hereditary: Poster Presentations - Proffered Abstracts Source Type: research

Abstract IA25: Deep sequencing of circulating tumor DNA for personalized cancer detection and monitoring
Circulating tumor DNA (ctDNA) represents a promising biomarker for sensitive, specific, and dynamic detection of disease burden in cancer patients. Additionally, ctDNA analysis allows non-invasive access to cancer genomes and therefore can be used for non-invasive tumor genotyping and monitoring of resistance mutations. In this presentation I will describe technical aspects of ctDNA detection and emerging clinical results from recent studies employing ctDNA analysis.Citation Format: Max Diehn. Deep sequencing of circulating tumor DNA for personalized cancer detection and monitoring. [abstract]. In: Proceedings of the AACR ...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Diehn, M. Tags: Monitoring Metastasis and CTCs: Oral Presentations - Invited Abstracts Source Type: research

Abstract B25: BET bromodomain inhibition targets adaptive responses to lapatinib in HER2-positive breast cancer
Small molecule kinase inhibitors that target oncogene-driven cancers often elicit dramatic initial clinical responses, but adaptive responses from the kinome and transcriptome limit their efficacy and generate resistance. Such adaptive bypass responses are driven by the disruption of regulatory feedback and feedforward loops that govern many signaling networks. To understand these responses in the context of HER2-addicted cancer, we used a chemical proteomics method to assay whole-kinome activation dynamics in cells treated with the small molecule HER2/EGFR tyrosine kinase inhibitor lapatinib. We observed a rapid reactivat...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Stuhlmiller, T. J., Miller, S. M., Zawistowski, J. S., Duncan, J. S., Angus, S. P., Granger, D. A., Reuther, R. A., Collins, K. A. L., Shawn, G. M., Kuan, P.-F., Chen, X., Sciaky, N., Johnson, G. L. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A25: Cytometric atlas of the human breast: Comprehensive characterization reveals 12 distinct cell populations
Since formulation of the cellular theory in the early 19th century—relatively not so long ago—it has become universally recognized that tissues and organisms are formed and shaped by cells of many different types, all operating in beautiful harmony. Many mechanisms of this orchestration remain largely a mystery to this day, yet are important for us to understand if we are to fully comprehend fundamental processes in disease, especially one as formidable and perplexing as cancer. In the current era of progressive technological advances, many areas of biology are converging, and we now recognize and expect differ...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Hines, W. C., Carr, A., Thi, K., Wan, Z., Pe'er, D., Bissell, M. J. Tags: Differentiation Hierarchy and Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract IA24: A stem cell program in early human metastatic breast cancer cells
In this study we used single-cell analysis to demonstrate that the initial disseminating metastatic cells resemble stem cells in their gene expression. We exploited patient-derived xenograft (PDX) models of human breast cancer to analyze metastatic cells in peripheral tissues. We developed a highly sensitive FACS-based assay to isolate and enumerate these metastatic cells. The primary tumor cells were heterogeneous and expressed high levels of luminal differentiation genes The metastatic cells from tissues with a low metastatic burden showed increased expression of stem cell, EMT, pro-survival, and dormancy-associated gene...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Lawson, D., Kessenbrock, K., Werb, Z. Tags: Monitoring Metastasis and CTCs: Oral Presentations - Invited Abstracts Source Type: research

Abstract B24: Triple-negative breast cancer adaptive response to MEK inhibition is regulated by the induction of super-enhancers
A predominant mechanism by which cancer cells circumvent the action of targeted kinase inhibitors is the activation of bypass signaling networks that reactivate cellular proliferation. In triple negative breast cancer (TNBC), a chief component of the adaptive response to MEK inhibition is the transcriptional upregulation and activation of receptor tyrosine kinases (RTKs), which contributes to drug resistance by reactivating ERK signaling as well as by initiating growth signaling through other kinase nodes. The cohort of RTKs activated differs between TNBC molecular subtypes and is heterogeneous even among cell lines of the...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Zawistowski, J. S., Miller, S. M., Goulet, D. R., Stuhlmiller, T. J., Singh, D., Sciaky, N., Velarde, S. H., Angus, S. P., Johnson, G. L. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A24: Age- and lineage-dependent gene expression is maintained by microenvironment imposed epigenetic states in human mammary epithelial cells
Normal healthy tissues show changing patterns of gene expression as a consequence of aging, and there is a functional cost to these changes that can be relevant to disease pathology. The most obvious age-related disease in breast is cancer, with the large majority of newly diagnosed breast cancer occuring in women over 50. We have shown that breast gene expression changes that occur with age have functional consequences in the epithelial progenitor and differentiated cells, i.e, a decline of the myoepithelial lineage, loss of luminal cell specificity, and accumulation of differentiation defective multipotent progenitor cel...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Miyano, M., Stoiber, M., Stampfer, M., Brown, B., LaBarge, M. A. Tags: Differentiation Hierarchy and Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B23: Citral reduces ALDH1A3 activity in breast cancer: Potential applications in targeting breast cancer stem cells
Breast tumors contain a subpopulation of cells known as cancer stem cells (CSCs) which are highly tumorigenic, resistant to typical chemo- and radiotherapy, and express high levels of aldehyde dehydrogenase (ALDH) isoforms ALDH1A3 and ALDH1A1. These enzymes initiate retinoic acid (RA) signaling and potentially contribute to detoxification of chemotherapy. A compound that inhibits these enzymes could be used as an adjuvant therapy to target breast CSCs and/or re-sensitize this population to chemotherapy. In particular, there are no currently characterized inhibitors of the ALDH1A3 isoform, so twelve general ALDH inhibitors ...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Thomas, M. L., Coyle, K. M., Cruickshank, B., Giacomantonio, M., Wallace, M., Giacomantonio, C., Marcato, P. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A23: Human mammary luminal progenitor cells use cKIT-H2O2 interactions to regulate their growth
Hydrogen peroxides (H2O2) are known to activate multiple cell signaling pathways but the mechanisms involved and how they are differentially regulated in specific normal mammary cell types is unknown. The luminal progenitor (LP) fraction of cells of the normal human mammary gland are of particular interest in this regard because, compared to the basal cells (BCs), these cells consume more O2, sustain higher levels of ROS, and are more resistant to H2O2 levels by virtue of their repertoire of enzymes that reduce both ROS and oxidized nucleotide products of ROS. However, these features of normal human LPs are also accompanie...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Kannan, N., Shih, K., Dong, Y., Eirew, P., Knapp, D., Pellacani, D., Wang, H., Zeng, H., Eaves, C. Tags: Differentiation Hierarchy and Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B22: PSMD2 is a molecular marker for a poor prognosis and determines cancer stem cells traits in breast cancer
The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSCs that is also capable of differentiating into non-self -renewing cell populations that constitute the bulk tumor mass. These cells have stem cell characteristics and may play a role in tumorigenic growth, metastasis, and therapeutic resistance. Here we interrogated the oncogenic roles of PSMD2, a subunit of the 19S regulatory complex of proteasomes, as a constituent of a signature is a candidate oncogene in breast cancer. PSMD2 is required for breast CSCs proliferation both in vitro and in vivo, as shRNA-mediated PSMD2 silenc...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Jung, S.-Y., Jo, S., Kang, E., Noh, D.-Y., Han, W. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B21: Suppression of adaptive resistance mechanisms to trametinib by inhibition of BET bromodomains in TNBC
The RAF-MEK-ERK signaling pathway regulates the proliferation of Triple Negative Breast Cancer (TNBC). Although MEK inhibition by trametinib in TNBC cell lines and mouse models inhibits growth, the response is not durable and the tumor develops resistance. The lack of durability of targeted kinase inhibitors is a common problem in many tumor types due to induction of alternative bypass signaling pathways that lead to resistance. We have profiled the response of TNBC to MEK inhibition using trametinib in order to identify adaptive signaling pathways which drive resistance. We used a chemical proteomics method [multiplexed i...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Miller, S. M., Zawistowski, J. S., Stuhlmiller, T. J., Sciaky, N., Santos, C. M., Darr, D. B., Johnson, G. L. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract IA20: Genomics of a STAT1 knockout mouse model of human ER+ breast cancer
In conclusion, truncating mutations of Prlr drive tumor development in a model of human ERa+ breast cancer and should be considered as novel antitumor targets.Citation Format: Elaine Mardis, Obi L. Griffith, Ruby Chan Szeman, Malachi Griffith, Kilannin Krysiak, Zachary Skidmore, Jasreet Hundal, Julie A. Allen, Arthur Cora, Alexander P. Miceli, Heather Schmidt, Lee Trani, Krishna-Latha Kanchi, Christopher A. Miller, David E. Larson, Robert S. Fulton, Richard K. Wilson, Robert D. Schreiber. Genomics of a STAT1 knockout mouse model of human ER+ breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advan...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Mardis, E., Griffith, O. L., Szeman, R. C., Griffith, M., Krysiak, K., Skidmore, Z., Hundal, J., Allen, J. A., Cora, A., Miceli, A. P., Schmidt, H., Trani, L., Kanchi, K.-L., Miller, C. A., Larson, D. E., Fulton, R. S., Wilson, R. K., Schreiber, R. D. Tags: Animal Models: Oral Presentations - Invited Abstracts Source Type: research

Abstract B20: Combination of Ganoderma lucidum extract and erlotinib decreases IBC progression
Inflammatory breast cancer (IBC) is a rare, and the most lethal and aggressive type of advanced breast cancer. Despite many efforts to increase IBC treatment efficacy, prognosis of this cancer is very grim. IBC cells and tissues overexpress epidermal growth factor receptor (EGFR), and this is a poor prognostic factor in this disease. Erlotinib is a small oral EGFR tyrosine kinase inhibitor that causes reverse inhibition of the EGFR tyrosine kinase domain. However, Erlotinib resistance can reduce the efficacy of this treatment. Our published results demonstrate that the extract of medicinal mushroom, Ganoderma lucidum (GLE)...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Rios-Fuller, T. J., Suarez-Arroyo, I. J., Lacourt-Ventura, M., Maldonado, G., Cubano, L. A., Martinez-Montemayor, M. M. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A20: Decreased nuclear expression of the FRY protein identifies a subset of breast cancers with poor clinical outcomes
The goal of the present study was to determine if decreased nuclear expression of the human FRY protein can serve as a biomaker of breast cancer progression and outcomes. We previously identified the rat Fry gene as a putative mammary carcinoma susceptibility (Mcs) gene. We further demonstrated that FRY expression was decreased in several human breast cancer cell lines. Moreover, ectopic expression of wildtype Fry suppressed tumorigenicity of the triple negative MDA-MD-231 breast cancer cells in vitro and in vivo by promoting epithelial cell differentiation. To evaluate the contribution of altered FRY expression to the cli...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Zarbl, H., Graham, J. C., Takizawa, N., Fang, M., Gong, Z., Estrella, B., Ren, X. Tags: Differentiation Hierarchy and Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract IA19: Targeting the BCL-2 family in breast cancer
The steps taken to evade cell death are a recognized hallmark of cancer. Intense efforts over the last three decades have provided important insights into the molecular mechanisms that govern programmed cell death and how tumors recalibrate key survival pathways to sustain their growth. The pro-survival protein BCL-2 is overexpressed in approximately 75% of breast cancer, where it is has emerged as an important prognostic marker. Indeed, BCL-2 expression is a key component of the Oncotype DX assay. BCL-2 overexpression is even more prominent in luminal tumors (~85%), reflecting its estrogen-responsiveness. Other key pro-su...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Lindeman, G. J., Merino, D., Vaillant, F., Whittle, J. R., Lok, S. W., Shackleton, K., Visvader, J. E. Tags: Other Topics: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B19: MET and IL6 signaling in triple-negative breast cancer
Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers and is associated with advanced stage at diagnosis and poorer outcome compared to other breast cancer subtypes. There is an unmet need for targeted therapeutic strategies for TNBC patients since current treatment options are restricted to standard chemotherapy. Both receptor tyrosine kinase (RTK) and inflammatory signaling have been shown to promote cancer progression and are promising therapeutic targets. Our laboratory was the first to demonstrate that the MET receptor tyrosine kinase is highly expressed in TNBC. Hepatocyte growth factor (HGF), th...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Tovar, E. A., Sameni, M., Essenburg, C. J., Chalasani, A., Linklater, E. S., Cherba, D. M., Anbalagan, A., Winn, M. E., Sloane, B. F., Graveel, C. R. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A19: Stathmin plays a role in both normal and transformed mammary gland
Normal mammary gland is a highly dynamic organ and displays complex tissue architecture, precise breast epithelial cell hierarchy and lineage plasticity regulation. These features are thought to underlie the high degree of both inter- and intra-tumor heterogeneity of breast cancers (BC).We have recently made the observation that stathmin knock-out (STMKO) female mice do not breast feed their first litter. Stathmin (also called Oncoprotein 18, OP18) is a microtubule-destabilizing protein. It is overexpressed in many human malignancies, including breast cancer, especially in advanced/metastatic disease. The phenotype that we...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Segatto, I., Berton, S., D'Andrea, S., Baldassarre, G., Belletti, B. Tags: Differentiation Hierarchy and Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract IA18: Development of targeted therapeutics using patient-derived xenografts
Clinically, breast cancers are divided into three distinct groups: those that express the estrogen hormone receptor (ER+) (which typically also express the progesterone hormone receptor (PR+), those that are amplified or overexpress the ErbB2 (HER2) oncogene (HER2+), and those that express none of these three markers (termed triple negative breast cancer TNBC). Unlike ER+ and HER2+ breast cancers, there are currently no targeted therapies against TNBC. Thus, the development of targeted therapies for TNBC is an active area of research.Entry into the clinical trial pipeline is a major milestone in the process of drug develop...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Lewis, M. T. Tags: Animal Models: Oral Presentations - Invited Abstracts Source Type: research

Abstract A18: Expression of the tumor suppressor gene RARRES1 in the differentiation hierarchy of breast cancer is regulated by DNA methylation
The tumor-suppressive function of the retinoic acid (RA)-inducible gene, retinoic acid receptor responder 1 (RARRES1), has been reported in many cancer types; however, in inflammatory breast cancer, RARRES1 is pro-tumorigenic. Furthermore, high transcript levels of RARRES1 are associated with more aggressive triple-negative breast cancers (TNBCs) and poorer patient outcomes. This suggests that RARRES1 may also be oncogenic and requires investigation to determine its role in breast cancer.Expression analyses of 20 breast cancer cell lines (including 18 TNBC and two estrogen-receptor-positive cell lines) revealed that RARRES...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Coyle, K. M., Vidovic, D., Dean, C. A., Thomas, M. L., Sultan, M., Clements, D., Vaghar-Kashani, A., Wallace, M., Weaver, I., Giacomantonio, C. A., Helyer, L., Marcato, P. Tags: Differentiation Hierarchy and Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B17: Genetic deletion of sphingosine kinase 1 suppresses mouse breast tumor development in MMTV-neu transgenic model
Sphingosine kinase 1 (SphK1) phosphorylates pro-apoptotic sphingosine to form pro-survival sphingosine-1-phosphate (S1P), leading to cancer progression. In breast cancer, high levels of SphK1 mRNA are found in 80% of the patients, with average increase of 2-fold in breast tumors compared with normal tissue from the same patient. Recent studies suggest that SphK1 expression is associated with disease-free survival in ER-negative and HER2-positive breast tumors. In addition, inhibition of SphK1 in HER2-positive breast cancer cell line reduced S1P-induced HER2 and ERK1/2 activation. While these evidences suggest that SphK1 ma...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Shimizu, Y., Furuya, H., Tamashiro, P. M., Goodison, S., Chan, O., Pagano, I., Iino, K., Peres, R., Hokutan, K., Loo, L. W. M., Hernandez, B., Naing, A., Rosser, C. J., Kawamori, T. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract IA16: Clinical relevance of host immunity in breast cancer
The clinical relevance of the host immune system in breast cancer has long been unclear. Recently an appreciation of the biological heterogeneity of breast cancer has prompted investigation of the immune system's role in the different molecular breast cancer subtypes. A robust association between a more favourable prognosis and the presence of high levels of lymphocytic infiltration has been found in early-stage triple negative and HER2-positive breast cancer. These infiltrates seem to represent favorable anti-tumor immune responses, suggesting that activation of host immunity will be important for improving survival outco...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Loi, S. Tags: Other Topics: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B16: Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer
Triple negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. Cancer genome sequencing studies focusing on TNBC failed to identify novel recurrently mutated cancer-driving genes, obviating immediate opportunities for targeted therapeutic development. Here we have identified BET bromodomain inhibitors (BBDIs) as promising novel therapeutic agents in TNBC. Specifically, we have found that TNBC cells are significantly and preferentially growth inhibited by BBDIs (e.g., JQ1) with IC50s in the low nM range compared to luminal breast cancer cells. The growth of ...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Shu, S., Lin, C., He, H. H., Witwicki, R., Roberts, J., Tabassum, D., Liang, Y., Ekram, M., Doherty, E., Brown, J., Mohammed, H., D'Santos, C., McKeown, M., Ott, C., Qi, J., Ni, M., Rao, P., Duarte, M., Wu, S.-Y., Chiang, C.-M., Young, R., Carroll, J., Lo Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A16: Loss of Hugl1 induces an EGF-dependent cellular transdifferentiation
Maintenance of cell polarity and tissue architecture are essential in preventing neoplasia. Three different protein complexes control cellular polarity, including the Par3/aPKC/Par6 complex, the Crumbs/Pals/Patj complex and the Scribble/Dlg/Lgl complex. Of these, only the loss of Lgl promotes massive tissue growth and cellular migration in Drosophila as well as altered cellular polarity. Humans have two well-conserved homologs, Hugl1 and Hugl2. Expression of Hugl1 is downregulated, lost, or mutated in many cancers, including colorectal, endometrial, hepatocellular carcinoma, malignant melanomas, and breast cancer. We have ...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Greenwood, E., Ebertz, D., Fabiano, A., Schroeder, J. A. Tags: Differentiation Hierarchy and Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract IA15: Immune control of breast cancer metastasis
Twenty to thirty percent of breast cancer patients eventually develop metastasis despite receiving state-of-the-art therapies. Clearly, identifying better ways to eliminate micro-metastatic tumor cells is paramount to eradicating death from breast cancer. We now know that every tumor is unique and that each tumor is heterogenous. Tumors hijack multiple, redundant pathways to survive and grow, and evolve resistance under selective pressure from therapy. Moreover, micro-metastatic cancer cells may be dormant and resistant to therapy. Thus, traditional approaches to treat cancer and prevent metastatic recurrences don't work f...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Welm, A. L. Tags: Tumor Microenvironment and Immunotherapy: Oral Presentations - Invited Abstracts Source Type: research

Abstract B15: Semaphorin 7a exerts pleiotropic effects to promote breast tumor progression
Understanding what drives breast tumor progression is of utmost importance for blocking tumor metastasis. We have identified that semaphorin 7a is a potent driver of breast tumor progression. Semaphorin 7a is a GPI membrane anchored protein that promotes attachment and spreading in multiple cell types. We observe that increased expression of SEMA7A occurs in ~45%human breast cancers and its upregulation is associated with decreased overall and distant metastasis free survival. In both in vitro and in vivo models, shRNA mediated silencing reveals roles for semaphorin 7a in the promotion of breast cancer cell growth, motilit...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Black, S., Nelson, A., Gurule, N., Futscher, B., Lyons, T. R. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A15: Using genetic and pharmacological methods to explore role of the methyltransferase Ezh2 in mouse mammary tumorigenesis
ErbB2 (HER2/Neu) is a receptor tyrosine kinase over expressed in 20-30% of primary human breast cancer cancer, and correlated with poor clinical outcome. However, the mechanisms through which ErbB2 contributes to tumorigenesis and poor patients prognosis is unclear. Over the last decade, several lines of evidence have demonstrated that the transformation of a normal epithelial cells to a malignant phenotype requires the accumulation of multiple genetics and epigenetic events, including post translational modifications of histones. Enhancer of Zeste 2 (Ezh2) is a polycomb group protein that, as a part of the PRC2 complex me...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Hirukawa, A., Smith, H., Muller, W. Tags: Animal Models: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B14: Targeting the intratumoral heterogeneity of receptor tyrosine kinases in breast cancer
Breast cancers display a remarkable phenotypic diversity that is exploited to promote both tumor progression and therapeutic resistance. Recent studies in several types of cancer have highlighted the significance of intratumoral heterogeneity on both innate and acquired resistance to tyrosine kinase inhibitors (TKIs). Tumor plasticity is supported by the heterogeneous expression of receptor tyrosine kinases (RTKs) and the robustness that the overlapping signaling networks provide. Therefore a thorough understanding of the intratumoral heterogeneity is necessary for the development of effective therapeutic strategies.The re...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Tovar, E. A., Linklater, E. S., Essenburg, C. J., Madaj, Z., Cherba, D. M., Winn, M. E., Korkaya, H., Boerner, J. L., Graveel, C. R. Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A14: Hedgehog inhibition delays cancer growth in C3(1)/Tag transgenic murine mammary carcinoma model
In 1941 Apperly hypothesized that differential sunlight exposure is the cause of the latitudinal gradient in breast cancer mortality, and subsequently the effect was postulated to be due to the tumor inhibitory properties of skin produced vitamin D3. We first tested this latitudinal hypotheses using the C3(1)/Tag transgenic murine mammary carcinoma model and found that ultraviolet radiation (UVR) significantly prolongs tumor-free and overall survival but that dietary D3 has no such effect. The mechanism of this anti-mammary carcinogenesis effect of UVR is unclear but there is evidence that D3 is a potent inhibitor of the h...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Makarova, A. M., KC, S., Dolorito, J. A., Khaimskiy, Y. I., Epstein, E. H. Tags: Animal Models: Poster Presentations - Proffered Abstracts Source Type: research