Defining Cancer Subpopulations by Adaptive Strategies Rather Than Molecular Properties Provides Novel Insights into Intratumoral Evolution
Ongoing intratumoral evolution is apparent in molecular variations among cancer cells from different regions of the same tumor, but genetic data alone provide little insight into environmental selection forces and cellular phenotypic adaptations that govern the underlying Darwinian dynamics. In three spontaneous murine cancers (prostate cancers in TRAMP and PTEN mice, pancreatic cancer in KPC mice), we identified two subpopulations with distinct niche construction adaptive strategies that remained stable in culture: (i) invasive cells that produce an acidic environment via upregulated aerobic glycolysis; and (ii) noninvasi...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Arig Ibrahim-Hashim, Mark Robertson-Tessi, Pedro M. Enriquez-Navas, Mehdi Damaghi, Yoganand Balagurunathan, Jonathan W. Wojtkowiak, Shonagh Russell, Kam Yoonseok, Mark C. Lloyd, Marilyn M. Bui, Joel S. Brown, Alexander R.A. Anderson, Robert J. Gillies, Ro Tags: Integrated Systems and Technologies Source Type: research
Cellular Hierarchy as a Determinant of Tumor Sensitivity to Chemotherapy
Chemotherapy has been shown to enrich cancer stem cells in tumors. Recently, we demonstrated that administration of chemotherapy to human bladder cancer xenografts could trigger a wound-healing response that mobilizes quiescent tumor stem cells into active proliferation. This phenomenon leads to a loss of sensitivity to chemotherapy partly due to an increase in the number of tumor stem cells, which typically respond to chemotherapy-induced cell death less than more differentiated cells. Different bladder cancer xenografts, however, demonstrate differential sensitivities to chemotherapy, the basis of which is not understood...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Ignacio A. Rodriguez-Brenes, Antonina V. Kurtova, Christopher Lin, Yu-Cheng Lee, Jing Xiao, Martha Mims, Keith Syson Chan, Dominik Wodarz Tags: Integrated Systems and Technologies Source Type: research
Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non-Small Cell Lung Cancer Patients
The duration and magnitude of clinical response are unpredictable in ALK-rearranged non–small cell lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop resistance. Here, we evaluated whether circulating tumor cells (CTC) with aberrant ALK-FISH patterns [ALK-rearrangement, ALK-copy number gain (ALK-CNG)] monitored on crizotinib could predict progression-free survival (PFS) in a cohort of ALK-rearranged patients. Thirty-nine ALK-rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively. Blood samples were collected at baseline and at an e...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Emma Pailler, Marianne Oulhen, Isabelle Borget, Jordi Remon, Kirsty Ross, Nathalie Auger, Fanny Billiot, Maud Ngo Camus, Frederic Commo, Colin R. Lindsay, David Planchard, Jean–Charles Soria, Benȷamin Besse, Francoise Farace Tags: Clinical Studies Source Type: research
Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer
In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ2 tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55.3% in luminal A tumors. In 40.2% of cases, luminal A tumors converted to luminal B tumors, whereas in 14.3% of cases luminal A and B tumors converted to HER2-E tumors. We identified 47 genes that were expressed differenti...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Juan M. Ceȷalvo, Eduardo Martinez de Duenas, Patricia Galvan, Susana Garcia–Recio, Octavio Burgues Gasion, Laia Pare, Silvia Antolin, Rosella Martinello, Isabel Blancas, Barbara Adamo, Angel Guerrero–Zotano, Montserrat Munoz, Paolo Nuci Tags: Clinical Studies Source Type: research
A Pyrrole-Imidazole Polyamide Is Active against Enzalutamide-Resistant Prostate Cancer
We reported previously that a pyrrole-imidazole (Py-Im) polyamide designed to bind the consensus androgen response element half-site has antitumor activity against hormone-sensitive prostate cancer. In enzalutamide-resistant LREX' cells, Py-Im polyamide interfered with both AR- and GR-driven gene expression, whereas enzalutamide interfered with only that of AR. Genomic analyses indicated immediate interference with the AR transcriptional pathway. Long-term treatment with Py-Im polyamide demonstrated a global decrease in RNA levels consistent with inhibition of transcription. The polyamide was active against two enzalutamid...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Alexis A. Kurmis, Fei Yang, Timothy R. Welch, Nicholas G. Nickols, Peter B. Dervan Tags: Priority Report Source Type: research
Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection
This report is the result of a one-day meeting held on May 4, 2016 with officials from the National Cancer Institute, the FDA, members of the American Society of Image-Guided Surgery, and members of the World Molecular Imaging Society, which discussed consensus methods for FDA-directed human testing and approval of investigational optical imaging devices as well as contrast agents for surgical applications. The goal of this workshop was to discuss FDA approval requirements and the expectations for approval of these novel drugs and devices, packaged separately or in combination, within the context of optical surgical naviga...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Willemieke S. Tummers, Jason M. Warram, Kiranya E. Tipirneni, John Fengler, Paula Jacobs, Lalitha Shankar, Lori Henderson, Betsy Ballard, Brian W. Pogue, Jamey P. Weichert, Michael Bouvet, Jonathan Sorger, Christopher H. Contag, John V. Frangioni, Michael Tags: Meeting Report Source Type: research
Whither Radioimmunotherapy: To Be or Not To Be?
Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive results in preclinical experiments and in clinical trials conducted in radiosensitive malignancies, particularly B-cell lymphomas. Two “first-generation,” directly radiolabeled anti-CD20 antibodies, 131iodine-tositumomab and 90yttrium-ibritumomab tiuxetan, were FDA-approved more than a decade ago but have been little utilized because of a variety of medical, financial, and logistic obstacles. Newer technologies employing multistep “pretargeting” methods, particularly those utilizing bispecific antibodies, have greatly enhanced the the...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Damian J. Green, Oliver W. Press Tags: Perspective Source Type: research
Master Transcriptional Regulators in Cancer: Discovery via Reverse Engineering Approaches and Subsequent Validation
Reverse engineering of transcriptional networks using gene expression data enables identification of genes that underpin the development and progression of different cancers. Methods to this end have been available for over a decade and, with a critical mass of transcriptomic data in the oncology arena having been reached, they are ever more applicable. Extensive and complex networks can be distilled into a small set of key master transcriptional regulators (MTR), genes that are very highly connected and have been shown to be involved in processes of known importance in disease. Interpreting and validating the results of s...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Bruce Moran, Arman Rahman, Katja Palonen, Fiona T. Lanigan, William M. Gallagher Tags: Reviews Source Type: research
Genomic Instability in Cancer: Teetering on the Limit of Tolerance
Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection, and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared with intermediate levels under this threshold. This has be...
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Noemi Andor, Carlo C. Maley, Hanlee P. Ji Tags: Reviews Source Type: research
Highlights from Recent Cancer Literature
(Source: Cancer Research)
Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Tags: Breaking Advances Source Type: research
Correction: EGFL6 Regulates the Asymmetric Division, Maintenance, and Metastasis of ALDH+ Ovarian Cancer Cells
(Source: Cancer Research)
Source: Cancer Research - April 13, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Correction: Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia
(Source: Cancer Research)
Source: Cancer Research - April 13, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Correction: SENP1 deSUMOylates and Regulates Pin1 Protein Activity and Cellular Function
(Source: Cancer Research)
Source: Cancer Research - April 13, 2017 Category: Cancer & Oncology Tags: Corrections Source Type: research
Cyp24a1 Attenuation Limits Progression of BrafV600E-Induced Papillary Thyroid Cancer Cells and Sensitizes Them to BRAFV600E Inhibitor PLX4720
In this study, we investigated the role of CYP24A1 on malignant progression of a murine model of BrafV600E-induced papillary thyroid cancer (PTC). Mice harboring wild-type Cyp24a1 (BVECyp24a1-wt) developed PTC at 5 weeks of age. Mice harboring a homozygous deletion of Cyp24a1 (BVECyp24a1-null) exhibited a 4-fold reduction in tumor growth. Notably, we found the tumorigenic potential of BVECyp24a1-null-derived tumor cells to be nearly abolished in immunocompromised nude mice. This phenotype was associated with downregulation of the MAPK, PI3K/Akt, and TGFβ signaling pathways and a loss of epithelial–mesenchymal transition...
Source: Cancer Research - April 13, 2017 Category: Cancer & Oncology Authors: Minȷing Zou, Essa Y. Baitei, Huda A. BinEssa, Futwan A. Al–Mohanna, Ranȷit S. Parhar, Rene St–Arnaud, Shioko Kimura, Catrin Pritchard, Ali S. Alzahrani, Abdullah M. Assiri, Brian F. Meyer, Yufei Shi Tags: Tumor and Stem Cell Biology Source Type: research
Prominent Oncogenic Roles of EVI1 in Breast Carcinoma
Overexpression of the EVI1 oncogene is associated typically with aggressive myeloid leukemia, but is also detectable in breast carcinoma where its contributions are unexplored. Analyzing a tissue microarray of 608 breast carcinoma patient specimens, we documented EVI1 overexpression in both estrogen receptor–positive (ER+) and estrogen receptor–negative (ER−) breast carcinomas. Here, we report prognostic relevance of EVI1 overexpression in triple-negative breast carcinoma but not in the HER2-positive breast carcinoma subset. In human breast cancer cells, EVI1 silencing reduced proliferation, apoptosis resistance, and...
Source: Cancer Research - April 13, 2017 Category: Cancer & Oncology Authors: Hui Wang, Thorsten Schaefer, Martina Konantz, Martin Braun, Zsuzsanna Varga, Anna M. Paczulla, Selina Reich, Francis Jacob, Sven Perner, Holger Moch, Tanja N. Fehm, Lothar Kanz, Klaus Schulze-Osthoff, Claudia Lengerke Tags: Tumor and Stem Cell Biology Source Type: research
