Stresses drive a cancer's initiation, progression and metastasis: Critical comments on the book "Cancer Bioinformatics"

2015 ◽  
Vol 13 (02) ◽  
pp. 1571002
Author(s):  
Chao Liu ◽  
Chi Zhang ◽  
Jing Su ◽  
Dongsheng Zhang ◽  
Sha Cao
Keyword(s):  
Cancer Biology ◽  
Evolutionary Process ◽  
Cancer Tissue ◽  
Cancer Evolution ◽  
Neoplastic Tissue ◽  
Oncogenic Mutations ◽  
Cancer Initiation ◽  
Metastatic Sites ◽  
Omic Data ◽  
Cancer Bioinformatics

"Cancer Bioinformatics" is a new book published in 2014 by Springer. This 14-chapter book offers a quite unique and potentially controversial view about what drives a cancer to initiate, progress, metastasize and develop in an accelerated manner in metastatic sites. The book treats cancer as an evolutionary process of a diseased tissue (rather than cells) in an increasingly more challenging microenvironment; and discusses the various stresses encountered by a neoplastic tissue and their roles in (driving) cancer initiation, progression, metastasis and post-metastatic development. Most of the discussions are made based on discoveries through mining cancer tissue omic data. In contrast to the on-going theories that cancers are the result of genomic mutations, the book clearly downplays the roles of genomic mutations, particularly oncogenic mutations, in cancer formation and progression. Throughout the book, the authors made special efforts in conveying their overarching view that cancer is a pathway to cell survival under certain stresses, and cell proliferation is either the result or a side-effect of survival processes when evolving to overcome the stresses. While the book is presented in an informatics style, it is actually a book of cancer biology focused on how information can be derived from cancer omic data to address a variety of basic cancer biology questions. Compared to other cancer biology books, this book is clearly less detail-oriented but more holistic and spans the entire range of cancer evolution.

scholarly journals Molecular Biology and Evolution of Cancer: From Discovery to Action

2019 ◽  
Vol 37 (2) ◽  
pp. 320-326 ◽  
Author(s):  
Jason A Somarelli ◽  
Heather Gardner ◽  
Vincent L Cannataro ◽  
Ella F Gunady ◽  
Amy M Boddy ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cancer Biology ◽  
Circulatory System ◽  
Evolutionary Process ◽  
Deep Understanding ◽  
The Body ◽  
Ecological Niches ◽  
Cell Populations ◽  
Cancer Evolution ◽  
Metastatic Sites

Abstract Cancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites. Efforts to prevent or delay cancer evolution—and progression—require a deep understanding of the underlying molecular evolutionary processes. Herein we discuss a suite of concepts and tools from evolutionary and ecological theory that can inform cancer biology in new and meaningful ways. We also highlight current challenges to applying these concepts, and propose ways in which incorporating these concepts could identify new therapeutic modes and vulnerabilities in cancer.

Single-Cell Epigenomics Reveals Mechanisms of Cancer Progression

2022 ◽  
Vol 6 (1) ◽  
Author(s):  
Lindsay M. LaFave ◽  
Rachel Savage ◽  
Jason D. Buenrostro
Keyword(s):  
Single Cell ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Annual Review ◽  
Publication Date ◽  
Cancer Evolution ◽  
Regulatory State ◽  
Cellular Functions ◽  
Cancer Initiation ◽  
Gene Regulatory

Cancer initiation is driven by the cooperation between genetic and epigenetic aberrations that disrupt gene regulatory programs critical to maintain specialized cellular functions. After initiation, cells acquire additional genetic and epigenetic alterations influenced by tumor-intrinsic and -extrinsic mechanisms, which increase intratumoral heterogeneity, reshape the cell's underlying gene regulatory network, and promote cancer evolution. Furthermore, environmental or therapeutic insults drive the selection of heterogeneous cell states, with implications for cancer initiation, maintenance, and drug resistance. The advancement of single-cell genomics has begun to uncover the full repertoire of chromatin and gene expression states (cell states) that exist within individual tumors. These single-cell analyses suggest that cells diversify in their regulatory states upon transformation by co-opting damage-induced and nonlineage regulatory programs that can lead to epigenomic plasticity. Here, we review these recent studies related to regulatory state changes in cancer progression and highlight the growing single-cell epigenomics toolkit poised to address unresolved questions in the field. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Early and multiple origins of metastatic lineages within primary tumors

2016 ◽  
Vol 113 (8) ◽  
pp. 2140-2145 ◽  
Author(s):  
Zi-Ming Zhao ◽  
Bixiao Zhao ◽  
Yalai Bai ◽  
Atila Iamarino ◽  
Stephen G. Gaffney ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cancer Biology ◽  
Tumor Development ◽  
Evolutionary Process ◽  
Driver Mutations ◽  
Cancer Evolution ◽  
Driver Genes ◽  
Genetic Changes ◽  
Primary Tumors ◽  
Multiple Origins

Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases.

scholarly journals Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefania Nobili ◽  
Antonella Mannini ◽  
Astrid Parenti ◽  
Chiara Raggi ◽  
Andrea Lapucci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Biology ◽  
Cancer Cell Line ◽  
Cancer Tissue ◽  
Endoplasmic Reticulum Membrane ◽  
Mcf 7

AbstractInvasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women’s health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER−/PR−/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24−/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within − 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.

Gotta catch ‘em all: the microscale quest to understand cancer biology

2016 ◽  
Vol 8 (12) ◽  
pp. 1203-1207 ◽  
Author(s):  
Zhenwei Ma ◽  
Christopher Moraes
Keyword(s):  
Cancer Biology ◽  
Recent Advances ◽  
Cancer Initiation ◽  
Insight Into

We highlight recent advances in the innovative use of microscale engineered technologies to gain new insight into the integrative biophysical mechanisms that drive cancer initiation and progression.

scholarly journals Skin Cancers and the Contribution of Rho GTPase Signaling Networks to Their Progression

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4362
Author(s):  
Alessandra Pecora ◽  
Justine Laprise ◽  
Manel Dahmene ◽  
Mélanie Laurin
Keyword(s):  
Skin Cancer ◽  
Cell Carcinoma ◽  
Cancer Biology ◽  
Rho Gtpase ◽  
Signaling Networks ◽  
Molecular Events ◽  
Skin Cancers ◽  
Cancer Initiation ◽  
Cytoskeletal Dynamics ◽  
Genetic Perturbations

Skin cancers are the most common cancers worldwide. Among them, melanoma, basal cell carcinoma of the skin and cutaneous squamous cell carcinoma are the three major subtypes. These cancers are characterized by different genetic perturbations even though they are similarly caused by a lifelong exposure to the sun. The main oncogenic drivers of skin cancer initiation have been known for a while, yet it remains unclear what are the molecular events that mediate their oncogenic functions and that contribute to their progression. Moreover, patients with aggressive skin cancers have been known to develop resistance to currently available treatment, which is urging us to identify new therapeutic opportunities based on a better understanding of skin cancer biology. More recently, the contribution of cytoskeletal dynamics and Rho GTPase signaling networks to the progression of skin cancers has been highlighted by several studies. In this review, we underline the various perturbations in the activity and regulation of Rho GTPase network components that contribute to skin cancer development, and we explore the emerging therapeutic opportunities that are surfacing from these studies.

scholarly journals Germ Cell Tumor Molecular Heterogeneity Revealed Through Analysis of Primary and Metastasis Pairs

2020 ◽  
pp. 1307-1320
Author(s):  
Michael L. Cheng ◽  
Mark T.A. Donoghue ◽  
François Audenet ◽  
Nathan C. Wong ◽  
Eugene J. Pietzak ◽  
...  
Keyword(s):  
Germ Cell ◽  
Somatic Mutations ◽  
Germ Cell Tumors ◽  
Molecular Heterogeneity ◽  
Targeted Next Generation Sequencing ◽  
Variants Of Unknown Significance ◽  
Resistant Disease ◽  
Oncogenic Mutations ◽  
Dna Copy Number Alterations ◽  
Metastatic Sites

PURPOSE Although primary germ cell tumors (GCTs) have been extensively characterized, molecular analysis of metastatic sites has been limited. We performed whole-exome sequencing and targeted next-generation sequencing on paired primary and metastatic GCT samples in a patient cohort enriched for cisplatin-resistant disease. PATIENTS AND METHODS Tissue sequencing was performed on 100 tumor specimens from 50 patients with metastatic GCT, and sequencing of plasma cell-free DNA was performed for a subset of patients. RESULTS The mutational landscape of primary and metastatic pairs from GCT patients was highly discordant (68% of all somatic mutations were discordant). Whereas genome duplication was common and highly concordant between primary and metastatic samples, only 25% of primary-metastasis pairs had ≥ 50% concordance at the level of DNA copy number alterations (CNAs). Evolutionary-based analyses revealed that most mutations arose after CNAs at the respective loci in both primary and metastatic samples, with oncogenic mutations enriched in the set of early-occurring mutations versus variants of unknown significance (VUSs). TP53 pathway alterations were identified in nine cisplatin-resistant patients and had the highest degree of concordance in primary and metastatic specimens, consistent with their association with this treatment-resistant phenotype. CONCLUSION Analysis of paired primary and metastatic GCT specimens revealed significant molecular heterogeneity for both CNAs and somatic mutations. Among loci demonstrating serial genetic evolution, most somatic mutations arose after CNAs, but oncogenic mutations were enriched in the set of early-occurring mutations as compared with VUSs. Alterations in TP53 were clonal when present and shared among primary-metastasis pairs.

scholarly journals Mutant Allele Imbalance in Cancer

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Craig M. Bielski ◽  
Barry S. Taylor
Keyword(s):  
Cancer Biology ◽  
Mutant Allele ◽  
Tumor Biology ◽  
Cellular Level ◽  
Driver Mutations ◽  
Annual Review ◽  
Publication Date ◽  
Cancer Evolution ◽  
Allele Imbalance ◽  
And Function

The search for somatic mutations that drive the initiation and progression of human tumors has dominated recent cancer research. While much emphasis has been placed on characterizing the prevalence and function of driver mutations, comparatively less is known about their serial genetic evolution. Indeed, study of this phenomenon has largely focused on tumor-suppressor genes recessive at the cellular level or mechanisms of resistance in tumors with mutant oncogenes targeted by therapy. There is, however, a growing appreciation that despite a decades-old presumption of heterozygosity, changes in mutant oncogene zygosity are common and drive dosage and stoichiometry changes that lead to selective growth advantages. Here, we review the recent progress in understanding mutant allele imbalance and its implications for tumor biology, cancer evolution, and response to anticancer therapy. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Exploiting Cancer’s Tactics to Make Cancer a Manageable Chronic Disease

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1649
Author(s):  
Kambiz Afrasiabi ◽  
Mark E. Linskey ◽  
Yi-Hong Zhou
Keyword(s):  
Radiation Therapy ◽  
Chronic Disease ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Cancer Therapeutics ◽  
Cytotoxic Agents ◽  
Cancer Evolution ◽  
Treatment Protocols ◽  
Regulatory Pathways ◽  
Surgical Technology

The history of modern oncology started around eighty years ago with the introduction of cytotoxic agents such as nitrogen mustard into the clinic, followed by multi-agent chemotherapy protocols. Early success in radiation therapy in Hodgkin lymphoma gave birth to the introduction of radiation therapy into different cancer treatment protocols. Along with better understanding of cancer biology, we developed drugs targeting cancer-related cellular and genetic aberrancies. Discovery of the crucial role of vasculature in maintenance, survival, and growth of a tumor opened the way to the development of anti-angiogenic agents. A better understanding of T-cell regulatory pathways advanced immunotherapy. Awareness of stem-like cancer cells and their role in cancer metastasis and local recurrence led to the development of drugs targeting them. At the same time, sequential and rapidly accelerating advances in imaging and surgical technology have markedly increased our ability to safely remove ≥90% of tumor cells. While we have advanced our ability to kill cells from multiple directions, we have still failed to stop most types of cancer from recurring. Here we analyze the tactics employed in cancer evolution; namely, chromosomal instability (CIN), intra-tumoral heterogeneity (ITH), and cancer-specific metabolism. These tactics govern the resistance to current cancer therapeutics. It is time to focus on maximally delaying the time to recurrence, with drugs that target these fundamental tactics of cancer evolution. Understanding the control of CIN and the optimal state of ITH as the most important tactics in cancer evolution could facilitate the development of improved cancer therapeutic strategies designed to transform cancer into a manageable chronic disease.

scholarly journals Unique Roles of Sphingolipids in Selected Malignant and Nonmalignant Lesions of Female Reproductive System

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Paweł Knapp ◽  
Karolina Chomicz ◽  
Magdalena Świderska ◽  
Adrian Chabowski ◽  
Robert Jach
Keyword(s):  
Cancer Biology ◽  
Membrane Lipids ◽  
Malignant Tumors ◽  
Chemotherapeutic Agents ◽  
Self Control ◽  
Cancer Tissue ◽  
Control Mechanisms ◽  
Ceramide Content ◽  
A Cell ◽  
Prevention Of Cancer

Cancer develops as a result of the loss of self-control mechanisms by a cell; it gains the ability to induce angiogenesis, becomes immortal and resistant to cell death, stops responding to growth suppressor signals, and becomes capable of invasion and metastasis. Sphingolipids—a family of membrane lipids—are known to play important roles in the regulation of cell proliferation, the response to chemotherapeutic agents, and/or prevention of cancer. Despite the underlying functions of sphingolipids in cancer biology, their metabolism in different malignant tumors is poorly investigated. Some studies showed marked differences in ceramide content between the tumor and the respective healthy tissue. Interestingly, the level of this sphingolipid could be either low or elevated, suggesting that the alterations in ceramide metabolism in cancer tissue may depend on the biology of the tumor. These processes are indeed related to the type of cancer, its stage, and histology status. In this paper we present the unique roles of bioactive sphingolipid derivative in selected gynecologic malignant and nonmalignant lesions.

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