James Valerinano Alvarez

Journal Article Cancer Res · March 14, 2025 Despite adjuvant treatment with endocrine therapies, estrogen receptor-positive (ER+) breast cancers recur in a significant proportion of patients. Recurrences are attributable to clinically undetectable endocrine-tolerant persister cancer cells that retai ... Full text Link to item Cite

Correction: Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants.

Journal Article PLoS Med · September 2024 [This corrects the article DOI: 10.1371/journal.pmed.0020313.]. ... Full text Link to item Cite

Optical imaging reveals chemotherapy-induced metabolic reprogramming of residual disease and recurrence.

Journal Article Sci Adv · April 5, 2024 Fewer than 20% of triple-negative breast cancer patients experience long-term responses to mainstay chemotherapy. Resistant tumor subpopulations use alternative metabolic pathways to escape therapy, survive, and eventually recur. Here, we show in vivo, lon ... Full text Link to item Cite

Immune cells in residual disease and recurrence.

Journal Article Trends Cancer · July 2023 Tumor recurrence following potentially curative therapy constitutes a major obstacle to achieving cures in patients with cancer. Recurrent tumors frequently arise from a population of residual cancer cells - also referred to as minimal residual disease (RD ... Full text Link to item Cite

In vivo metabolic imaging identifies lipid vulnerability in a preclinical model of Her2+/Neu breast cancer residual disease and recurrence.

Journal Article NPJ Breast Cancer · September 26, 2022 Recurrent cancer cells that evade therapy is a leading cause of death in breast cancer patients. This risk is high for women showing an overexpression of human epidermal growth factor receptor 2 (Her2). Cells that persist can rely on different substrates f ... Full text Link to item Cite

APOBEC Mutagenesis Inhibits Breast Cancer Growth through Induction of T cell-Mediated Antitumor Immune Responses.

Journal Article Cancer Immunol Res · January 2022 The APOBEC family of cytidine deaminases is one of the most common endogenous sources of mutations in human cancer. Genomic studies of tumors have found that APOBEC mutational signatures are enriched in the HER2 subtype of breast cancer and are associated ... Full text Link to item Cite

Therapy-Induced Dormancy and Residual Disease

Chapter · January 1, 2022 In many common epithelial cancers, such as breast and prostate cancer, the majority of deaths are caused by the survival and eventual recurrence of residual tumor cells after therapy. In many cases, residual tumors can survive for years or even decades pri ... Full text Cite

Context-dependent effects of whole-genome duplication during mammary tumor recurrence.

Journal Article Sci Rep · July 22, 2021 Whole-genome duplication (WGD) generates polyploid cells possessing more than two copies of the genome and is among the most common genetic abnormalities in cancer. The frequency of WGD increases in advanced and metastatic tumors, and WGD is associated wit ... Full text Link to item Cite

DDR2 upregulation confers ferroptosis susceptibility of recurrent breast tumors through the Hippo pathway.

Journal Article Oncogene · March 2021 Recurrent breast cancer presents significant challenges with aggressive phenotypes and treatment resistance. Therefore, novel therapeutics are urgently needed. Here, we report that murine recurrent breast tumor cells, when compared with primary tumor cells ... Full text Open Access Link to item Cite

G9a Promotes Breast Cancer Recurrence through Repression of a Pro-inflammatory Program.

Journal Article Cell Rep · November 3, 2020 Dysregulated gene expression is a common feature of cancer and may underlie some aspects of tumor progression, including tumor relapse. Here, we show that recurrent mammary tumors exhibit global changes in gene expression and histone modifications and acqu ... Full text Link to item Cite

Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence.

Journal Article Nat Commun · October 6, 2020 The survival and recurrence of residual tumor cells following therapy constitutes one of the biggest obstacles to obtaining cures in breast cancer, but it remains unclear how the clonal composition of tumors changes during relapse. We use cellular barcodin ... Full text Link to item Cite

RIPK3 upregulation confers robust proliferation and collateral cystine-dependence on breast cancer recurrence.

Journal Article Cell Death Differ · July 2020 The molecular and genetic basis of tumor recurrence is complex and poorly understood. RIPK3 is a key effector in programmed necrotic cell death and, therefore, its expression is frequently suppressed in primary tumors. In a transcriptome profiling between ... Full text Link to item Cite

NRF2 activation promotes the recurrence of dormant tumour cells through regulation of redox and nucleotide metabolism.

Journal Article Nat Metab · April 2020 The survival and recurrence of dormant tumour cells following therapy is a leading cause of death in cancer patients. The metabolic properties of these cells are likely distinct from those of rapidly growing tumours. Here we show that Her2 down-regulation ... Full text Link to item Cite

In vivo metabolic imaging reveals mitochondrial membrane potential reprogramming following Her2-targeted therapy and dormant disease

Conference Optics InfoBase Conference Papers · January 1, 2020 We performed in intravital fluorescent microscopy in a preclinical cancer dormancy model to capture key changes in mitochondrial activity associated with Her2 treated breast cancer both acutely and in a residual disease state. ... Cite

Optical Imaging of Glucose Uptake and Mitochondrial Membrane Potential to Characterize Her2 Breast Tumor Metabolic Phenotypes.

Journal Article Mol Cancer Res · July 2019 With the large number of women diagnosed and treated for breast cancer each year, the importance of studying recurrence has become evident due to most deaths from breast cancer resulting from tumor recurrence following therapy. To mitigate this, cellular a ... Full text Link to item Cite

CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors.

Journal Article Elife · April 16, 2019 Over half of breast-cancer-related deaths are due to recurrence 5 or more years after initial diagnosis and treatment. This latency suggests that a population of residual tumor cells can survive treatment and persist in a dormant state for many years. The ... Full text Link to item Cite

bcSeq: an R package for fast sequence mapping in high-throughput shRNA and CRISPR screens.

Journal Article Bioinformatics · October 15, 2018 SUMMARY: CRISPR-Cas9 and shRNA high-throughput sequencing screens have abundant applications for basic and translational research. Methods and tools for the analysis of these screens must properly account for sequencing error, resolve ambiguous mappings am ... Full text Link to item Cite

Epigenetic silencing of tumor suppressor Par-4 promotes chemoresistance in recurrent breast cancer.

Journal Article J Clin Invest · October 1, 2018 Tumor relapse is the leading cause of death in breast cancer, largely due to the fact that recurrent tumors are frequently resistant to chemotherapy. We previously reported that downregulation of the proapoptotic protein Par-4 promotes tumor recurrence in ... Full text Link to item Cite

Abstract PR09: Clonal dynamics during breast cancer dormancy and recurrence

Conference Cancer Research · May 15, 2018 AbstractTumor progression is the process by which cancer cells acquire increasingly aggressive characteristics, including resistance to therapies and an increased propensity to metastasize. The combination o ... Full text Cite

Foxo-dependent Par-4 Upregulation Prevents Long-term Survival of Residual Cells Following PI3K-Akt Inhibition.

Journal Article Mol Cancer Res · April 2018 Tumor recurrence is a leading cause of death and is thought to arise from a population of residual cells that survive treatment. These residual cancer cells can persist, locally or at distant sites, for years or decades. Therefore, understanding the pathwa ... Full text Link to item Cite

Oncogene pathway activation in mammary tumors dictates FDG-PET uptake.

Journal Article Cancer Res · December 15, 2014 Increased glucose utilization is a hallmark of human cancer that is used to image tumors clinically. In this widely used application, glucose uptake by tumors is monitored by positron emission tomography of the labeled glucose analogue 2[(18)F]fluoro-2-deo ... Full text Link to item Cite

SPSB1 promotes breast cancer recurrence by potentiating c-MET signaling.

Journal Article Cancer Discov · July 2014 UNLABELLED: Breast cancer mortality is principally due to tumor recurrence; however, the molecular mechanisms underlying this process are poorly understood. We now demonstrate that the suppressor of cytokine signaling protein SPSB1 is spontaneously upregul ... Full text Link to item Cite

Par-4 downregulation promotes breast cancer recurrence by preventing multinucleation following targeted therapy.

Journal Article Cancer cell · July 2013 Most deaths from breast cancer result from tumor recurrence, but mechanisms underlying tumor relapse are largely unknown. We now report that Par-4 is downregulated during tumor recurrence and that Par-4 downregulation is necessary and sufficient to promote ... Full text Cite

Autocrine prolactin induced by the Pten-Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways.

Journal Article Genes & development · October 2012 Extrapituitary prolactin (Prl) is produced in humans and rodents; however, little is known about its in vivo regulation or physiological function. We now report that autocrine prolactin is required for terminal mammary epithelial differentiation during pre ... Full text Cite

Oncogene addiction: Mouse models and clinical relevance for molecularly targeted therapies

Journal Article · January 1, 2012 Cancer results from the dysregulation of pathways controlling the growth, proliferation, differentiation, and survival of tumor cells, as well as fundamental alterations in the manner in which cells interact with their microenvironment (Hanahan and Weinber ... Full text Cite

Akt is required for Stat5 activation and mammary differentiation.

Journal Article Breast Cancer Res · 2010 INTRODUCTION: The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism, and is one of the most commonly activated pathways in human cancer. A role for Akt in epithelial differentiation, however, has not been establishe ... Full text Link to item Cite

Akt is required for Stat5 activation and mammary differentiation.

Journal Article Breast cancer research : BCR · 2010 The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism, and is one of the most commonly activated pathways in human cancer. A role for Akt in epithelial differentiation, however, has not been established. We previous ... Full text Cite

Singular value decomposition-based regression identifies activation of endogenous signaling pathways in vivo.

Journal Article Genome biology · January 2008 The ability to detect activation of signaling pathways based solely on gene expression data represents an important goal in biological research. We tested the sensitivity of singular value decomposition-based regression by focusing on functional interactio ... Full text Cite

mILC-ing the mouse mammary gland: A model for invasive lobular carcinoma.

Journal Article Cancer Cell · November 2006 Mouse models that faithfully recapitulate human cancers are indispensable tools for studying the molecular mechanisms of tumorigenesis and testing potential anticancer therapies. In this issue of Cancer Cell, Derksen et al. describe a new mouse model that ... Full text Link to item Cite

Cyclin D1 overexpression and response to bortezomib treatment in a breast cancer model.

Journal Article Journal of the National Cancer Institute · September 2006 BackgroundCyclin D1 is frequently overexpressed in breast cancer, and its overexpression is, surprisingly, associated with improved survival. One potential mechanism for this association involves signal transducer and activator of transcription 3 ... Full text Cite

Tyrosine phosphorylation is required for functional activation of disulfide-containing constitutively active STAT mutants.

Journal Article Biochemistry · May 2006 Aberrant activation of STAT transcription factors has been implicated in a variety of cancers. Constitutively active forms of STAT1 and STAT3 (STAT1C and STAT3C) have been developed to determine the effects of STAT activation in isolation from other cytoki ... Full text Cite

Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor.

Journal Article Cancer research · March 2006 Somatic mutations in the epidermal growth factor receptor (EGFR) occur frequently in lung cancer and confer sensitivity to EGFR kinase inhibitors gefitinib and erlotinib. These mutations, which occur in the kinase domain of the protein, also render EGFR co ... Full text Cite

Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants.

Journal Article PLoS medicine · November 2005 BackgroundSomatic mutations in the kinase domain of the epidermal growth factor receptor tyrosine kinase gene EGFR are common in lung adenocarcinoma. The presence of mutations correlates with tumor sensitivity to the EGFR inhibitors erlotinib and ... Full text Cite

Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors.

Journal Article Cancer Res · June 15, 2005 Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated in diverse human tumors and may play a direct role in malignant transformation. However, the full complement of target genes that STAT3 regulates to prom ... Full text Link to item Cite

Isolation of unique STAT5 targets by chromatin immunoprecipitation-based gene identification.

Journal Article J Biol Chem · December 24, 2004 STAT5a and STAT5b are two highly related transcription factors that control essential cellular functions. Several STAT5 targets are known, although it is likely that most remain uncharacterized. To identify a more complete set of STAT5-regulated genes, we ... Full text Link to item Cite

Genome-wide analysis of STAT target genes: elucidating the mechanism of STAT-mediated oncogenesis.

Journal Article Cancer Biol Ther · November 2004 Inappropriate activation of transcription factors is a common event in cancer. These transcription factors contribute to a malignant phenotype by regulating genes involved in cellular proliferation, survival, differentiation, angiogenesis, and invasion. An ... Full text Link to item Cite