Epigenetic regulation of cancer stem cell and tumorigenesis.
Abstract As a unique subpopulation of cancer cells, cancer stem cells (CSCs) acquire the resistance to conventional therapies and appear to be the prime cause of cancer recurrence. Like their normal counterparts, CSCs can renew themselves and generate differentiated progenies. Cancer stem cells are distinguished among heterogenous cancer cells by molecular markers and their capacity of efficiently forming new tumors composed of diverse and heterogenous cancer cells. Tumor heterogeneity can be inter- or intra-tumor, molecularly resulting from the accumulation of genetic and non-genetic alterations. Non-genetic alte...
Source: Advances in Cancer Research - July 30, 2020 Category: Cancer & Oncology Authors: Zhu K, Xie V, Huang S Tags: Adv Cancer Res Source Type: research

Cyclin D-CDK4/6 functions in cancer.
Abstract The mammalian cell cycle is driven by a complex of cyclins and their associated cyclin-dependent kinases (CDKs). Abnormal dysregulation of cyclin-CDK is a hallmark of cancer. D-type cyclins and their associated CDKs (CDK4 and CDK6) are key components of cell cycle machinery in driving G1 to S phase transition via phosphorylating and inactivating the retinoblastoma protein (RB). A body of evidence shows that the cyclin Ds-CDKs axis plays a critical role in cancer through various aspects, such as control of proliferation, senescence, migration, apoptosis, and angiogenesis. CDK4/6 dual-inhibitors show signif...
Source: Advances in Cancer Research - July 30, 2020 Category: Cancer & Oncology Authors: Gao X, Leone GW, Wang H Tags: Adv Cancer Res Source Type: research

SPARC-p53: The double agents of cancer.
Abstract Cancer is a complex disease with high incidence and mortality rates. The important role played by the tumor microenvironment in regulating oncogenesis, tumor growth, and metastasis is by now well accepted in the scientific community. SPARC is known to participate in tumor-stromal interactions and impact cancer growth in ambiguous ways, which either enhance or suppress cancer aggressiveness, in a context-dependent manner. p53 transcription factor, a well-established tumor suppressor, has been reported to promote tumor growth in certain situations, such as hypoxia, thus displaying a duality in its action. A...
Source: Advances in Cancer Research - July 30, 2020 Category: Cancer & Oncology Authors: Camacho D, Jesus JP, Palma AM, Martins SA, Afonso A, Peixoto ML, Pelham CJ, Moreno E, Gogna R Tags: Adv Cancer Res Source Type: research

Giants and monsters: Unexpected characters in the story of cancer recurrence.
Abstract Polyploid giant cancer cells (PGCC) constitute a dangerous subpopulation of cancer cells and are a driving force in cancer recurrence. These unique cells arise from diploid tumor cells in response to stress encountered in the tumor microenvironment or during cancer therapy. PGCC are greatly dedifferentiated, acquire pluripotency, and are able to replicate through a form of asymmetric division called neosis, which results in new populations that are themselves able to differentiate into new cell types or to re-establish tumors. Progeny tend to be more genetically unstable than the founding population due t...
Source: Advances in Cancer Research - July 30, 2020 Category: Cancer & Oncology Authors: White-Gilbertson S, Voelkel-Johnson C Tags: Adv Cancer Res Source Type: research

Ca2+ as a therapeutic target in cancer.
Abstract Ca2+ is a ubiquitous and dynamic second messenger molecule that is induced by many factors including receptor activation, environmental factors, and voltage, leading to pleiotropic effects on cell function including changes in migration, metabolism and transcription. As such, it is not surprising that aberrant regulation of Ca2+ signals can lead to pathological phenotypes, including cancer progression. However, given the highly context-specific nature of Ca2+-dependent changes in cell function, delineation of its role in cancer has been a challenge. Herein, we discuss the distinct roles of Ca2+ signaling ...
Source: Advances in Cancer Research - July 30, 2020 Category: Cancer & Oncology Authors: Gross S, Mallu P, Joshi H, Schultz B, Go C, Soboloff J Tags: Adv Cancer Res Source Type: research

Vascular mimicry: Triggers, molecular interactions and in vivo models.
Abstract Vascular mimicry is induced by a wide array of genes with functions related to cancer stemness, hypoxia, angiogenesis and autophagy. Vascular mimicry competent (VM-competent) cells that form de novo blood vessels are common in solid tumors facilitating tumor cell survival and metastasis. VM-competent cells display increased levels of vascular mimicry selecting for stem-like cells in an O2-gradient-dependent manner in deeply hypoxic tumor regions, while also aiding in maintaining tumor cell metabolism and stemness. Three of the principal drivers of vascular mimicry are EphA2, Nodal and HIF-1α, howeve...
Source: Advances in Cancer Research - July 30, 2020 Category: Cancer & Oncology Authors: Wechman SL, Emdad L, Sarkar D, Das SK, Fisher PB Tags: Adv Cancer Res Source Type: research

Biology, pathology, and therapeutic targeting of RAS.
Abstract RAS was identified as a human oncogene in the early 1980s and subsequently found to be mutated in nearly 30% of all human cancers. More importantly, RAS plays a central role in driving tumor development and maintenance. Despite decades of effort, there remain no FDA approved drugs that directly inhibit RAS. The prevalence of RAS mutations in cancer and the lack of effective anti-RAS therapies stem from RAS' core role in growth factor signaling, unique structural features, and biochemistry. However, recent advances have brought promising new drugs to clinical trials and shone a ray of hope in the field. He...
Source: Advances in Cancer Research - July 30, 2020 Category: Cancer & Oncology Authors: Rhett JM, Khan I, O'Bryan JP Tags: Adv Cancer Res Source Type: research

Roles for receptor tyrosine kinases in tumor progression and implications for cancer treatment.
Abstract Growth factors and their receptor tyrosine kinases (RTKs), a group of transmembrane molecules harboring cytoplasm-facing tyrosine-specific kinase functions, play essential roles in migration of multipotent cell populations and rapid proliferation of stem cells' descendants, transit amplifying cells, during embryogenesis and tissue repair. These intrinsic functions are aberrantly harnessed when cancer cells undergo intertwined phases of cell migration and proliferation during cancer progression. For example, by means of clonal expansion growth factors fixate the rarely occurring driver mutations, which ini...
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Ghosh S, Marrocco I, Yarden Y Tags: Adv Cancer Res Source Type: research

HER family in cancer progression: From discovery to 2020 and beyond.
Abstract The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases (RTKs) are among the first layer of molecules that receive, interpret, and transduce signals leading to distinct cancer cell phenotypes. Since the discovery of the tooth-lid factor-later characterized as the epidermal growth factor (EGF)-and its high-affinity binding EGF receptor, HER kinases have emerged as one of the commonly upregulated or hyperactivated or mutated kinases in epithelial tumors, thus allowing HER1-3 family members to regulate several hallmarks of cancer development and progression. Each member of the HE...
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Kumar R, George B, Campbell MR, Verma N, Paul AM, Melo-Alvim C, Ribeiro L, Pillai MR, da Costa LM, Moasser MM Tags: Adv Cancer Res Source Type: research

EGFR: An essential receptor tyrosine kinase-regulator of cancer stem cells.
Abstract The Epidermal Growth Factor Receptor (EGFR) is frequently expressed at elevated levels in different forms of cancer and expression often correlates positively with cancer progression and poor prognosis. Different mutant forms of this protein also contribute to cancer heterogeneity. A constitutively active form of EGFR, EGFRvIII is one of the most important variants. EGFR is responsible for the maintenance and functions of cancer stem cells (CSCs), including stemness, metabolism, immunomodulatory-activity, dormancy and therapy-resistance. EGFR regulates these pathways through several signaling cascades, an...
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Talukdar S, Emdad L, Das SK, Fisher PB Tags: Adv Cancer Res Source Type: research

In vivo modeling of the EGFR family in breast cancer progression and therapeutic approaches.
Abstract Modeling breast cancer through the generation of genetically engineered mouse models (GEMMs) has become the gold standard in the study of human breast cancer. Notably, the in vivo modeling of the epidermal growth factor receptor (EGFR) family has been key to the development of therapeutics and has helped better understand the signaling pathways involved in cancer initiation, progression and metastasis. The HER2/ErbB2 receptor is a member of the EGFR family and 20% of breast cancers are found to belong in the HER2-positive histological subtype. Historical and more recent advances in the field have shaped o...
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Simond AM, Muller WJ Tags: Adv Cancer Res Source Type: research

Advances in insulin-like growth factor biology and -directed cancer therapeutics.
Abstract The insulin and insulin-like growth factor (IGF) family of proteins are part of a complex network that regulates cell proliferation and survival. While this system is undoubtedly important in prenatal development and postnatal cell growth, members of this family have been implicated in several different cancer types. Increased circulating insulin and IGF ligands have been linked to increased risk of cancer incidence. This observation has led to targeting the IGF system as a therapeutic strategy in a number of cancers. This chapter aims to describe the well-characterized biology of the IGF1R system, outlin...
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Fettig LM, Yee D Tags: Adv Cancer Res Source Type: research

MET receptor in oncology: From biomarker to therapeutic target.
Abstract First discovered in the 1984, the MET receptor tyrosine kinase (RTK) and its ligand hepatocyte growth factor or HGF (also known as scatter factor or SF) are implicated as key players in tumor cell migration, proliferation, and invasion in a variety of cancers. This pathway also plays a key role during embryogenesis in the development of muscular and nervous structures. High expression of the MET receptor has been shown to correlate with poor prognosis and resistance to therapy. MET exon 14 splicing variants, initially identified by us in lung cancer, is actionable through various tyrosine kinase inhibitor...
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Malik R, Mambetsariev I, Fricke J, Chawla N, Nam A, Pharaon R, Salgia R Tags: Adv Cancer Res Source Type: research

Eph receptors as cancer targets for antibody-based therapy.
Abstract Receptor tyrosine kinases (RTKs) are integral membrane sensors that govern cell differentiation, proliferation and mobility, and enable rapid communication between cells and their environment. Of the 20 RTK subfamilies currently known, Eph receptors are the largest group. Together with their corresponding ephrin ligands, Eph receptors regulate a diverse array of physiologic processes including axonal guidance, bone remodeling, and immune cell development and trafficking. Deregulation of Eph signaling pathways is linked to cancer and other proliferative diseases and, because RTKs play critical roles in can...
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Tang FHF, Davis D, Arap W, Pasqualini R, Staquicini FI Tags: Adv Cancer Res Source Type: research

RTKs in pathobiology of head and neck cancers.
Abstract Non-communicable diseases contribute to 71% of the deaths worldwide, of which cancers rank second after cardiovascular diseases. Among all the cancers, head and neck cancers (HNC) are consequential in augmenting the global cancer incidence as well as mortality. Receptor tyrosine kinases (RTKs) are emphatic for the matter that they serve as biomarkers aiding the analysis of tumor progression and metastasis as well as diagnosis, prognosis and therapeutic progression in the patients. The extensive researches on HNC have made significant furtherance in numerous targeted therapies, but for the escalating thera...
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Nadhan R, Srinivas P, Pillai MR Tags: Adv Cancer Res Source Type: research

Advances in EGFR/HER2-directed clinical research on breast cancer.
Abstract The discovery of the HER2 molecules has embarked a series of investigations on the efficacy and safety of different types of anti-HER2 therapies for treating breast cancer, with the clinical pathway requiring a more detailed, more precise, and more dynamics therapeutic approaches due to the heterogeneity of the disease. As the "do more" and "do less" approaches are becoming more important to personalize treatment for early HER2-positive breast cancer, recent advances aim at tackling the advanced stage of the disease by using novel therapeutic agents and combination strategies. There ar...
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Chow LWC, Lie EF, Toi M Tags: Adv Cancer Res Source Type: research

Nuclear receptor tyrosine kinase transport and functions in cancer.
Abstract Signaling functions of plasma membrane-localized receptor tyrosine kinases (RTKs) have been extensively studied after they were first described in the mid-1980s. Plasma membrane RTKs are activated by extracellular ligands and cellular stress stimuli, and regulate cellular responses by activating the downstream effector proteins to initiate a wide range of signaling cascades in the cells. However, increasing evidence indicates that RTKs can also be transported into the intracellular compartments where they phosphorylate traditional effector proteins and non-canonical substrate proteins. In general, interna...
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Chen MK, Hsu JL, Hung MC Tags: Adv Cancer Res Source Type: research

Preface.
PMID: 32593408 [PubMed - in process] (Source: Advances in Cancer Research)
Source: Advances in Cancer Research - July 2, 2020 Category: Cancer & Oncology Authors: Kumar R, Fisher PB Tags: Adv Cancer Res Source Type: research

Racial/ethnic disparities in ovarian cancer research.
Abstract Ovarian cancer is one of the most fatal cancers diagnosed in women in the United States (U.S.). Data from national databases, including the Surveillance Epidemiology and End Results (SEER) program, show racial/ethnic differences in risk and survival of epithelial ovarian cancer with higher incidence among white women yet worse survival among African-American women compared to other racial/ethnic groups. The reasons for these differences are not well understood, but are likely multi-factorial. Epidemiologic studies suggest there may be some risk factor differences across racial/ethnic groups that would exp...
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Peres LC, Schildkraut JM Tags: Adv Cancer Res Source Type: research

Race differences in mobility status among prostate cancer survivors: The role of socioeconomic status.
The objective of this paper was to determine whether there were any race differences in mobility limitation among PCa survivors, and understand the impact of socioeconomic status (SES) on this relationship. Data consisted of 661 PCa survivors (296 Black and 365 White) from the Diagnosis and Decisions in Prostate Cancer Treatment Outcomes (DAD) Study. Mobility limitation was defined as PCa survivors who reported difficulty walking a quarter mile or up 1 flight of stairs. Race was based on the PCa survivors self-identification of either White or Black. SES consisted of education level (i.e., less than high school, high schoo...
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Thorpe RJ, Bruce MA, Howard DL, LaVeist TA Tags: Adv Cancer Res Source Type: research

Assessing an intervention to increase knowledge related to cervical cancer and the HPV vaccine.
Abstract Human papillomavirus (HPV) infection is the primary risk factor for cervical cancer. While the HPV vaccine significantly reduces the risk of HPV infection and subsequent cervical cancer diagnosis, underuse is linked to lack of knowledge of its effectiveness in preventing cervical cancer. The purpose of this study was to evaluate a cancer educational intervention (titled "MOVENUP") to improve knowledge of cervical cancer, HPV, and the HPV vaccine among predominantly African American communities in South Carolina. The MOVENUP cancer educational intervention was conducted among participants residin...
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Ford ME, Cannady K, Nahhas GJ, Knight KD, Chavis C, Crawford B, Malek AM, Martino E, Frazier S, Gathers A, Lawton C, Cartmell KB, Luque JS Tags: Adv Cancer Res Source Type: research

Patient barriers to cancer clinical trial participation and navigator activities to assist.
Abstract Clinical research is vital to the discovery of new cancer treatments that can enhance health and prolong life for cancer patients, but breakthroughs in cancer treatment are limited by challenges recruiting patients into cancer clinical trials (CT). Only 3-5% of cancer patients in the United States participate in a cancer CT and there are disparities in CT participation by age, race and gender. Strategies such as patient navigation, which is designed to provide patients with education and practical support, may help to overcome challenges of CT recruitment. The current study evaluated an intervention in wh...
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Cartmell KB, Bonilha HS, Simpson KN, Ford ME, Bryant DC, Alberg AJ Tags: Adv Cancer Res Source Type: research

Project PLACE: Enhancing community and academic partnerships to describe and address health disparities.
Abstract Achieving cancer health equity is a national imperative. Cancer is the second leading cause of death in the United States and in North Carolina (NC), where the disease disproportionately impacts traditionally underrepresented race and ethnic groups, those who live in rural communities, the impoverished, and medically disenfranchised and/or health-disparate populations at high-risk for cancer. These populations have worse cancer outcomes and are less likely to be participants in clinical research and trials. It is critical for cancer centers and other academic health centers to understand the factors that ...
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Barrett NJ, Ingraham KL, Bethea K, Hwa-Lin P, Chirinos M, Fish LJ, Randolph S, Zhang P, Le P, Harvey D, Godbee RL, Patierno SR Tags: Adv Cancer Res Source Type: research

Mighty men: A faith-based weight loss intervention to reduce cancer risk in African American men.
Abstract According to the American Cancer Society's guidelines on nutrition and physical activity for cancer prevention, weight control, eating practices and physical activity are second only to tobacco use as modifiable determinants of cancer risk. However, no evidence-based interventions have been targeted to African American men or tailored to individual African American men's preferences, needs or identities. The goal of this chapter is to describe the rationale for the components, aims and setting of Mighty Men: A Faith-Based Weight Loss Intervention for African American Men. We begin by discussing the ration...
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Griffith DM, Jaeger EC Tags: Adv Cancer Res Source Type: research

A primer for cancer research programs on defining and evaluating the catchment area and evaluating minority clinical trials recruitment.
Abstract National Cancer Institute (NCI) designated cancer centers are charged with reducing disparities, improving cancer-related health outcomes, and increasing clinical trial participation for the catchment area population. Succeeding in this endeavor requires a clear definition of each cancer center's geographic catchment area as well as the demographic characteristics of the populations residing in the catchment area. For this reason, the definition of the catchment area is now a required element of NCI grant applications. This primer provides detailed information related to the definition of cancer centers' ...
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Nguyen LH, Cook ED Tags: Adv Cancer Res Source Type: research

Age-related disparities in older women with breast cancer.
Abstract Improvements in breast cancer (BC) mortality rates have not been seen in the older adult community, and the fact that older adults are more likely to die from their cancer than younger women establishes a major health disparity. Studies have identified that despite typically presenting with more favorable histology, older women present with more advanced disease, which may be related in part to delayed diagnosis. This is supported by examination of screening practices in older adults. Older women have a worse prognosis than younger women in both early stage disease, and more advanced and metastatic diseas...
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Bagegni NA, Peterson LL Tags: Adv Cancer Res Source Type: research

Pubertal mammary development as a "susceptibility window" for breast cancer disparity.
Pubertal mammary development as a "susceptibility window" for breast cancer disparity. Adv Cancer Res. 2020;146:57-82 Authors: Krisanits B, Randise JF, Burton CE, Findlay VJ, Turner DP Abstract Factors such as socioeconomic status, age at menarche and childbearing patterns are components that have been shown to influence mammary gland development and establish breast cancer disparity. Pubertal mammary gland development is selected as the focus of this review, as it is identified as a "window of susceptibility" for breast cancer risk and disparity. Here we recognize non-Hispanic Whi...
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Krisanits B, Randise JF, Burton CE, Findlay VJ, Turner DP Tags: Adv Cancer Res Source Type: research

BMI, physical activity, and breast cancer subtype in white, black, and Sea Island breast cancer survivors.
JD, Whitfield KE, Esnaola NF, Cunningham JE Abstract Higher BMI, lower rates of physical activity (PA), and hormone receptor-negative breast cancer (BC) subtype are associated with poorer BC treatment outcomes. We evaluated the prevalence of high BMI, low PA level, and BC subtype among survivors with white/European American (EA) and African American (AA) ancestry, as well as a distinct subset of AAs with Sea Island/Gullah ancestry (SI). We used the South Carolina Central Cancer Registry to identify 137 (42 EAs, 66 AAs, and 29 SIs) women diagnosed with BC and who were within 6-21 months of diagnosis. We employed l...
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Ford ME, Bauza CE, Findlay VJ, Turner DP, Abraham LM, Moore LA, Magwood G, Alberg AJ, Gaymon K, Knight KD, Hilton E, Malek AM, Kramer RM, Peterson LL, Gregoski MJ, Bolick S, Hurley D, Mosley C, Hazelton TR, Burshell DR, Nogueira L, Mack F, Brown ET, Salle Tags: Adv Cancer Res Source Type: research

Preface.
PMID: 32241394 [PubMed - in process] (Source: Advances in Cancer Research)
Source: Advances in Cancer Research - April 4, 2020 Category: Cancer & Oncology Authors: Ford ME, Esnaola NF, Salley JD Tags: Adv Cancer Res Source Type: research

Atypical chemokine receptors in tumor cell growth and metastasis.
Abstract Atypical chemokine receptors (ACKRs) are seven-transmembrane cell surface protein receptors expressed in immune cells, normal mesenchymal cells, and several tumor cells. As of this writing, six ACKRs have been characterized by diverse activities. They bind both cysteine-cysteine (CC) type and cysteine-X-cysteine (CXC)-type chemokines, either alone, or together with a ligand bound-functional G-protein coupled (typical) chemokine receptor. The major structural difference between ACKRs and typical chemokine receptors is the substituted DRYLAIV amino acid motif in the second intracellular loop of the ACKR. Du...
Source: Advances in Cancer Research - February 25, 2020 Category: Cancer & Oncology Authors: Lokeshwar BL, Kallifatidis G, Hoy JJ Tags: Adv Cancer Res Source Type: research

Structure and function of β-arrestins, their emerging role in breast cancer, and potential opportunities for therapeutic manipulation.
Structure and function of β-arrestins, their emerging role in breast cancer, and potential opportunities for therapeutic manipulation. Adv Cancer Res. 2020;145:139-156 Authors: Shukla AK, Dwivedi-Agnihotri H Abstract β-Arrestins (βarrs) are multifunctional intracellular proteins with an ability to directly interact with a large number of cellular partners including the G protein-coupled receptors (GPCRs). βarrs contribute to multiple aspects of GPCR signaling, trafficking and downregulation. Considering the central involvement of GPCR signaling in the onset and progression of diver...
Source: Advances in Cancer Research - February 25, 2020 Category: Cancer & Oncology Authors: Shukla AK, Dwivedi-Agnihotri H Tags: Adv Cancer Res Source Type: research

The G protein coupled receptor CCR5 in cancer.
Abstract The G coupled protein receptor CC chemokine receptor type 5 (CCR5) has the unusual characteristic in humans of being a developmentally non-essential gene that participates in several pathological processes including infection with HIV (Dean et al., 1996; Gupta et al., 2019; Samson et al., 1996), progression of stroke (Joy et al., 2019), osteoporosis (Xie et al., 2019) and the metastasis of cancer (Jiao et al., 2018; Velasco-Velazquez et al., 2012, 2014) (Reviewed in: Jiao, Nawab, et al., 2019; Jiao, Wang, & Pestell, 2019). The importance of CCR5 in HIV led to recent genetic engineering of humans to re...
Source: Advances in Cancer Research - February 25, 2020 Category: Cancer & Oncology Authors: Upadhyaya C, Jiao X, Ashton A, Patel K, Kossenkov AV, Pestell RG Tags: Adv Cancer Res Source Type: research

Targeting G protein-coupled receptors in cancer therapy.
Abstract As basic research into GPCR signaling and its association with disease has come into fruition, greater clarity has emerged with regards to how these receptors may be amenable to therapeutic intervention. As a diverse group of receptor proteins, which regulate a variety of intracellular signaling pathways, research in this area has been slow to yield tangible therapeutic agents for the treatment of a number of diseases including cancer. However, recently such research has gained momentum based on a series of studies that have sought to define GPCR proteins dynamics through the elucidation of their crystal ...
Source: Advances in Cancer Research - February 25, 2020 Category: Cancer & Oncology Authors: Soond SM, Zamyatnin AA Tags: Adv Cancer Res Source Type: research

The diverse and complex roles of atypical chemokine receptors in cancer: From molecular biology to clinical relevance and therapy.
Szpakowska M Abstract Chemokines regulate directed cell migration, proliferation and survival and are key components in cancer biology. They exert their functions by interacting with seven-transmembrane domain receptors that signal through G proteins (GPCRs). A subgroup of four chemokine receptors known as the atypical chemokine receptors (ACKRs) has emerged as essential regulators of the chemokine functions. ACKRs play diverse and complex roles in tumor biology from tumor initiation to metastasis, including cancer cell proliferation, adherence to endothelium, epithelial-mesenchymal transition (EMT), extravasatio...
Source: Advances in Cancer Research - February 25, 2020 Category: Cancer & Oncology Authors: Sjöberg E, Meyrath M, Chevigné A, Östman A, Augsten M, Szpakowska M Tags: Adv Cancer Res Source Type: research

The Microbiome as a Component of the Tumor Microenvironment.
acute;ri Z, Bai P Abstract Microbes, which live in the human body, affect a large set of pathophysiological processes. Changes in the composition and proportion of the microbiome are associated with metabolic diseases (Fulbright et al., PLoS Pathog 13:e1006480, 2017; Maruvada et al., Cell Host Microbe 22:589-599, 2017), psychiatric disorders (Macfabe, Glob Adv Health Med 2:52-66, 2013; Kundu et al., Cell 171:1481-1493, 2017), and neoplastic diseases (Plottel and Blaser, Cell Host Microbe 10:324-335, 2011; Schwabe and Jobin, Nat Rev Cancer 13:800-812, 2013; Zitvogel et al., Cell 165:276-287, 2016). However, the num...
Source: Advances in Cancer Research - February 8, 2020 Category: Cancer & Oncology Authors: Kovács T, Mikó E, Ujlaki G, Sári Z, Bai P Tags: Adv Exp Med Biol Source Type: research

Macroenvironment-gene-microenvironment interactions in ultraviolet radiation-induced melanomagenesis.
Abstract Cutaneous malignant melanoma is one of the few major cancers that continue to exhibit a positive rate of increase in the developed world. A wealth of epidemiological data has undisputedly implicated ultraviolet radiation (UVR) from sunlight and artificial sources as the major risk factor for melanomagenesis. However, the molecular mechanisms of this cause-and-effect relationship remain murky and understudied. Recent efforts on multiple fronts have brought unprecedented expansion of our knowledge base on this subject and it is now clear that melanoma is caused by a complex interaction between genetic predi...
Source: Advances in Cancer Research - July 28, 2019 Category: Cancer & Oncology Authors: Mo X, Preston S, Zaidi MR Tags: Adv Cancer Res Source Type: research

MDA-9/Syntenin: An emerging global molecular target regulating cancer invasion and metastasis.
Abstract With few exceptions, metastasis is the terminal stage of cancer with limited therapeutic options. Metastasis consists of numerous phenotypic and genotypic alterations of cells that are directly and indirectly induced by multiple intrinsic (cellular) and extrinsic (micro-environmental) factors. To metastasize, a cancer cell often transitions from an epithelial to mesenchymal morphology (EMT), modifies the extracellular matrix, forms emboli and survives in the circulation, escapes immune surveillance, adheres to sites distant from the initial tumor and finally develops a blood supply (angiogenesis) and colo...
Source: Advances in Cancer Research - July 28, 2019 Category: Cancer & Oncology Authors: Das SK, Sarkar D, Emdad L, Fisher PB Tags: Adv Cancer Res Source Type: research

Expression of costimulatory and inhibitory receptors in FoxP3+ regulatory T cells within the tumor microenvironment: Implications for combination immunotherapy approaches.
Abstract The unprecedented success of immune checkpoint inhibitors has given rise to a rapidly growing number of immuno-oncology agents undergoing preclinical and clinical development and an exponential increase in possible combinations. Defining a clear rationale for combinations by identifying synergies between immunomodulatory pathways has therefore become a high priority. Immunosuppressive regulatory T cells (Tregs) within the tumor microenvironment (TME) represent a major roadblock to endogenous and therapeutic tumor immunity. However, Tregs are also essential for the maintenance of immunological self-toleran...
Source: Advances in Cancer Research - July 28, 2019 Category: Cancer & Oncology Authors: Toker A, Ohashi PS Tags: Adv Cancer Res Source Type: research

Capsaicinoids enhance chemosensitivity to chemotherapeutic drugs.
Abstract Cytotoxic chemotherapy is the mainstay of cancer treatment. Conventional chemotherapeutic agents do not distinguish between normal and neoplastic cells. This leads to severe toxic side effects, which may necessitate the discontinuation of treatment in some patients. Recent research has identified key molecular events in the initiation and progression of cancer, promoting the design of targeted therapies to selectively kill tumor cells while sparing normal cells. Although, the side effects of such drugs are typically milder than conventional chemotherapies, some off-target effects still occur. Another seri...
Source: Advances in Cancer Research - July 28, 2019 Category: Cancer & Oncology Authors: Friedman JR, Richbart SD, Merritt JC, Perry HE, Brown KC, Akers AT, Nolan NA, Stevenson CD, Hurley JD, Miles SL, Tirona MT, Valentovic MA, Dasgupta P Tags: Adv Cancer Res Source Type: research

Marine natural products in the discovery and development of potential pancreatic cancer therapeutics.
Abstract Pancreatic cancer one of the most deadly cancers and is an increasingly significant concern for global health. The death rates for pancreatic cancer have changed little over time, even with recent expansions of first-line drugs to treat pancreatic cancer there has been little improvement in patient prognosis. Any improvements in treatment strategies will come as a much-needed reprieve to patients diagnosed with this uniquely-challenging disease. Greater attention is needed regarding the identification and development of novel chemotherapeutic strategies with unique mechanisms of action. The marine environ...
Source: Advances in Cancer Research - July 28, 2019 Category: Cancer & Oncology Authors: Wang X, Hamann MT Tags: Adv Cancer Res Source Type: research

Cancer stem cells in breast and prostate: Fact or fiction?
Abstract Since the introduction of the cancer stem cell (CSC) hypothesis, accumulating evidence shows that most cancers present stem-like niches. However, therapies aimed at targeting this niche have not been as successful as expected. New evidence regarding CSCs hierarchy, similarities with normal tissue stem cells and cell plasticity might be key in understanding their role in cancer biology and how to efficiently eliminate them. In this Chapter, we discuss what is known in breast and prostate CSCs from their initial discoveries to the current therapeutic efforts in the field. Future challenges towards better CS...
Source: Advances in Cancer Research - July 28, 2019 Category: Cancer & Oncology Authors: Sampayo RG, Bissell MJ Tags: Adv Cancer Res Source Type: research

Racial disparities, cancer and response to oxidative stress.
Abstract At the intersection of genetics, biochemistry and behavioral sciences, there is a largely untapped opportunity to consider how ethnic and racial disparities contribute to individual sensitivity to reactive oxygen species and how these might influence susceptibility to various cancers and/or response to classical cancer treatment regimens that pervasively result in the formation of such chemical species. This chapter begins to explore these connections and builds a platform from which to consider how the disciplines can be strengthened further. PMID: 31349903 [PubMed - in process] (Source: Advances in Cancer Research)
Source: Advances in Cancer Research - July 28, 2019 Category: Cancer & Oncology Authors: Zhang J, Ye ZW, Townsend DM, Hughes-Halbert C, Tew KD Tags: Adv Cancer Res Source Type: research

PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer.
e;a X Abstract PP2A is a highly conserved eukaryotic serine/threonine protein phosphatase of the PPP family of phosphatases with fundamental cellular functions. In cells, PP2A targets specific subcellular locations and substrates by forming heterotrimeric holoenzymes, where a core dimer consisting of scaffold (A) and catalytic (C) subunits complexes with one of many B regulatory subunits. PP2A plays a key role in positively and negatively regulating a myriad of cellular processes, as it targets a very sizable fraction of the cellular substrates phosphorylated on Ser/Thr residues. This review focuses on insights ma...
Source: Advances in Cancer Research - July 28, 2019 Category: Cancer & Oncology Authors: Fowle H, Zhao Z, Graña X Tags: Adv Cancer Res Source Type: research

Clinical and translational advances in esophageal squamous cell carcinoma.
an KA Abstract Esophageal squamous cell carcinoma (ESCC) is among the most deadly forms of human malignancy characterized by late stage diagnosis, metastasis, therapy resistance and frequent recurrence. Clinical management of ESCC remains challenging and the disease presently lacks approved targeted therapeutics. However, emerging data from recent clinical and translational investigations hold great promise for future progress toward improving patient outcomes in this deadly disease. Here, we review current clinical perspectives in ESCC epidemiology, pathophysiology, and clinical care, highlighting recent advances...
Source: Advances in Cancer Research - July 28, 2019 Category: Cancer & Oncology Authors: Reichenbach ZW, Murray MG, Saxena R, Farkas D, Karassik EG, Klochkova A, Patel K, Tice C, Hall TM, Gang J, Parkman HP, Ward SJ, Tétreault MP, Whelan KA Tags: Adv Cancer Res Source Type: research

Translation of cancer immunotherapy from the bench to the bedside.
er WH Abstract The tremendous success of immune checkpoint blockades has revolutionized cancer management. Our increased understanding of the cell types that compose the tumor microenvironment (TME), including those of the innate and adaptive immune system, has helped to shape additional immune modulatory strategies in cancer care. Pre-clinical and clinical investigations targeting novel checkpoint interactions and key pathways that regulate cancer immunity continue to increase rapidly. Various combinatorial drug regimens are being tested in attempt to achieve durable response and survival rates of patients with c...
Source: Advances in Cancer Research - June 18, 2019 Category: Cancer & Oncology Authors: Guo Q, Huang F, Goncalves C, Del Rincón SV, Miller WH Tags: Adv Cancer Res Source Type: research

Co-stimulatory and co-inhibitory pathways in cancer immunotherapy.
Abstract Cancer remains the leading cause of death worldwide. Traditional treatments such as surgery, radiation, and chemotherapy have had limited efficacy, especially with late stage cancers. Cancer immunotherapy and targeted therapy have revolutionized how cancer is treated, especially in patients with late stage disease. In 2013 cancer immunotherapy was named the breakthrough of the year, partially due to the established efficacy of blockade of CTLA-4 and PD-1, both T cell co-inhibitory molecules involved in tumor-induced immunosuppression. Though early trials promised success, toxicity and tolerance to immunot...
Source: Advances in Cancer Research - June 18, 2019 Category: Cancer & Oncology Authors: O'Neill RE, Cao X Tags: Adv Cancer Res Source Type: research

Immunometabolism: A new target for improving cancer immunotherapy.
Abstract Fundamental metabolic pathways are essential for mammalian cells to provide energy, precursors for biosynthesis of macromolecules, and reducing power for redox regulation. While dysregulated metabolism (e.g., aerobic glycolysis also known as the Warburg effect) has long been recognized as a hallmark of cancer, recent discoveries of metabolic reprogramming in immune cells during their activation and differentiation have led to an emerging concept of "immunometabolism." Considering the recent success of cancer immunotherapy in the treatment of several cancer types, increasing research efforts are ...
Source: Advances in Cancer Research - June 18, 2019 Category: Cancer & Oncology Authors: Guo C, Chen S, Liu W, Ma Y, Li J, Fisher PB, Fang X, Wang XY Tags: Adv Cancer Res Source Type: research

Impact of the microbiome on cancer progression and response to anti-cancer therapies.
Abstract Humans are a colonized with trillions of commensal microorganisms which exert a profound effect on normal host physiology and immune function through an abundance of genetic and metabolic by-products. Although the commensal microbiome has beneficial functions to host physiology, perturbations of the composition of the commensal microbiome or the homeostatic mucosal environment can lead to the induction of immune pathology and systemic inflammation. In the context of cancer progression or response to immune therapy, this inflammation can be detrimental, resulting in tumor growth and the promotion of immune...
Source: Advances in Cancer Research - June 18, 2019 Category: Cancer & Oncology Authors: Buchta Rosean C, Feng TY, Azar FN, Rutkowski MR Tags: Adv Cancer Res Source Type: research

Immunotherapy in breast cancer: Current status and future directions.
Abstract Breast cancer, one of the leading causes of death in women in the United States, challenges therapeutic success in patients due to tumor heterogeneity, treatment resistance, metastasis and disease recurrence. Knowledge of immune system involvement in normal breast development and breast cancer has led to extensive research into the immune landscape of breast cancer and multiple immunotherapy clinical trials in breast cancer patients. However, poor immunogenicity and T-cell infiltration along with heightened immunosuppression in the tumor microenvironment have been identified as potential challenges to the...
Source: Advances in Cancer Research - June 18, 2019 Category: Cancer & Oncology Authors: Basu A, Ramamoorthi G, Jia Y, Faughn J, Wiener D, Awshah S, Kodumudi K, Czerniecki BJ Tags: Adv Cancer Res Source Type: research

Can CpG methylation serve as surrogate markers for immune infiltration in cancer?
Abstract Recent reports describe how genome-wide transcriptional analysis of cancer tissues can be exploited to identify molecular signatures of immune infiltration in cancer. We hypothesize that immune infiltration in cancer may also be defined by changes in certain epigenetic signatures. In this context, a primary objective is to identify site-specific CpG markers whose levels of methylation may be highly indicative of known transcriptional markers of immune infiltration such as GZMA, PRF1, T cell receptor genes, PDCD1, and CTLA4. This has been accomplished by integrating genome-wide transcriptional expression a...
Source: Advances in Cancer Research - June 18, 2019 Category: Cancer & Oncology Authors: Bacolod MD, Barany F, Fisher PB Tags: Adv Cancer Res Source Type: research