The recent advances in functional genomics have discovered that a large number of long non-coding RNAs (lncRNAs) are pervasively transcribed from the human genome. Increasing evidence further indicates that lncRNAs are important for gene expression during cell differentiation and development through various mechanisms such as nuclear organization, post-transcription regulation, alternative splicing, and epigenetic regulation. Thus, aberrant expression of lncRNAs can cause abnormality in those cellular functions and lead to various pathological conditions. One of such fatal consequences is cancer metastasis which is responsible for more than 90% of cancer-related deaths. A good understanding of how lncRNAs regulate different genetic and epigenetic changes during different stages of cancer metastasis is important not only for general cancer biology but also for identifi cation of novel biomarkers and therapeutic targets for treatment of metastatic cancer. A significant progress has been made regarding the role of lncRNAs in cancer for past several years. In this study, we first discuss general functions of lncRNAs and then highlight recent fi ndings of how lncRNAs impact cancer metastasis, and finally we provide our perspectives on clinical implications of lncRNAs.

The knowledge that the body possesses natural defenses to combat cancer existed long before the modern period, with multiple anecdotal reports of tumors miraculously disappearing, sometimes spontaneously or after a febrile or infectious episode. Spontaneous tumor regression of untreated malignant tumors is currently a well-accepted albeit rare phenomenon, and it is recognized that immunosuppression is associated with a higher cancer risk. The treatment of bladder carcinoma by intravesical administration of live attenuated Bacillus Calmette-Guérin bacteria was shown to be very effective in 1976 and is now standard treatment. Effective immunity against cancer involves complex interactions between the tumor, the host, and the environment. Cancer immunotherapy uses various strategies to augment tumor immunity and represents a paradigm shift in treating cancer, since attention has become more focused on the “biologic passport” of the individual tumor rather than the site of origin of the tumor. The different types of cancer immunotherapies discussed here include biologic modifiers, such as cytokines and vaccines, adoptive cell therapies, oncolytic viruses, and antibodies against immune checkpoint inhibitors, such as the co-inhibitory T-cell receptor PD-1 and one of its ligands, programmed death-ligand 1.

Extracellular matrix (ECM) is an essential component of the tumor microenvironment. Cancer development and progression are associated with increased ECM deposition and crosslink. The chemical and physical signals elicited from ECM are necessary for cancer cell proliferation and invasion. It is well recognized that stromal cells are a major source of ECM proteins. However, recent studies showed that cancer cells are also an active and important component in ECM remodeling. Cancer cells deposit a significant amount of collagen, fibronectin, and tenascin C (TNC). Recent studies demonstrate that these cancer cell-derived ECM proteins enhance cancer cell survival and promote cancer cell colonization at distant sites. ECM-related enzymes and chaperone proteins, such as prolyl-4-hydroxylase, lysyl-hydroxylase, lysyl oxidase, and heat shock protein 47, are also highly expressed in cancer cells. Inhibition of these enzymes significantly reduces cancer growth, invasion, and metastasis. These factors suggest that the cancer cell-derived ECM is crucial for cancer progression and metastasis. Therefore, targeting these ECM proteins and ECM-related enzymes is a potential strategy for cancer treatment.

Circulating tumor cells (CTCs) have become a blistering topic of discussion for oncologists because of their tremendous potential in the diagnosis and treatment of cancer. Over the past few years, they have been doled with quite an amount of research in this area understanding that CTCs are shed from tumors and circulate in the bloodstream. This process can also occur at an early stage of cancer. The major limitation in isolation of CTCs is their availability in limited numbers. Hence, many techniques have been developed and are under continuous improvement to enhance their efficacy of CTC isolation and enumeration. They have shown their potentiality to not just indicate the presence of a tumor but also to provide us with its core information. They have also proven to be useful in detecting minor subgroups of cells present in the primary tissue which might eventually be the cause of treatment resistance or relapse of the disease. Hence, detecting and characterizing CTCs can definitely become an inevitable step in treating solid tumor malignancies. In this review, we have tried to comprehend the basics of CTCs including isolation, detection, characterization, and molecular mechanism of their circulation in the blood stream. We have mostly focused on the significance of CTCs in diagnosis and therapies of four most common types of cancers, namely, breast, prostate, lung, and colorectal. This review provides the coverage of most of the advancements with regards to different tumor malignancies and their probable use in predicting outcomes of the disease to realize the concept of personalized medicine.

Central nervous system (CNS) cancer is a devastating illness with unmet therapeutic needs. Establishing biomarkers that have the potential to guide accurate CNS cancer diagnosis or are helpful in predicting disease progression or therapy response is of great interest. Cerebrospinal fluid (CSF) has been extensively targeted for the detection of molecules that might be useful markers for cancer detection. However, so far very few of such markers have found a standardized routine clinical application. This review examines the current scientific knowledge about the biochemical elements in the CSF that have been reported in the literature as brain cancer biomarkers and highlight reasons why the role of most markers is not yet established in the managment of CNS tumors.

The discovery of Toll-like receptors (TLRs) about 20 years ago was a remarkable achievement not only in the field of immunology but also in the field of medicine. The TLRs are a family of pattern recognition receptors which play an important role in immune responses by recognizing pathogen-associated molecular patterns. The TLRs also recognize danger-associated molecular patterns, which are associated with some diseases such as cancer. Recent evidence shows that TLRs are expressed not only in immune cells but also in tumor cells. The TLRs appear to play a role in tumor progression and treatment. Most likely, TLR activation has an impact on the initiation, development and treatment of tumors by modulating the inflammatory microenvironment. However, the activation of TLRs contributes to both inhibition and promotion of various tumors, with unclear underlying mechanisms. In this review article, the authors elucidate their current understanding about the role of TLRs in tumor progression, as well as the recent progress in utilizing TLR agonists as potential therapeutic agents in cancer treatment.

The knowledge that the body possesses natural defenses to combat cancer existed long before the modern period, with multiple anecdotal reports of tumors miraculously disappearing, sometimes spontaneously or after a febrile or infectious episode. Spontaneous tumor regression of untreated malignant tumors is currently a well-accepted albeit rare phenomenon, and it is recognized that immunosuppression is associated with a higher cancer risk. The treatment of bladder carcinoma by intravesical administration of live attenuated Bacillus Calmette-Guérin bacteria was shown to be very effective in 1976 and is now standard treatment. Effective immunity against cancer involves complex interactions between the tumor, the host, and the environment. Cancer immunotherapy uses various strategies to augment tumor immunity and represents a paradigm shift in treating cancer, since attention has become more focused on the “biologic passport” of the individual tumor rather than the site of origin of the tumor. The different types of cancer immunotherapies discussed here include biologic modifiers, such as cytokines and vaccines, adoptive cell therapies, oncolytic viruses, and antibodies against immune checkpoint inhibitors, such as the co-inhibitory T-cell receptor PD-1 and one of its ligands, programmed death-ligand 1.

Circulating tumor cells (CTCs) have become a blistering topic of discussion for oncologists because of their tremendous potential in the diagnosis and treatment of cancer. Over the past few years, they have been doled with quite an amount of research in this area understanding that CTCs are shed from tumors and circulate in the bloodstream. This process can also occur at an early stage of cancer. The major limitation in isolation of CTCs is their availability in limited numbers. Hence, many techniques have been developed and are under continuous improvement to enhance their efficacy of CTC isolation and enumeration. They have shown their potentiality to not just indicate the presence of a tumor but also to provide us with its core information. They have also proven to be useful in detecting minor subgroups of cells present in the primary tissue which might eventually be the cause of treatment resistance or relapse of the disease. Hence, detecting and characterizing CTCs can definitely become an inevitable step in treating solid tumor malignancies. In this review, we have tried to comprehend the basics of CTCs including isolation, detection, characterization, and molecular mechanism of their circulation in the blood stream. We have mostly focused on the significance of CTCs in diagnosis and therapies of four most common types of cancers, namely, breast, prostate, lung, and colorectal. This review provides the coverage of most of the advancements with regards to different tumor malignancies and their probable use in predicting outcomes of the disease to realize the concept of personalized medicine.

The therapeutic limitations of conventional chemotherapeutic drugs present a challenge for cancer therapy; these shortcomings are largely attributed to the ability of cancer cells to repopulate and metastasize after initial therapies. Compelling evidence suggests that cancer stem cells (CSCs) have a crucial impact in current shortcomings of cancer therapy because they are largely responsible for tumor initiation, relapse, metastasis, and chemo-resistance. Thus, a better understanding of the properties and mechanisms underlying CSC resistance to treatments is necessary to improve patient outcomes and survival rates. In this review, the authors characterize and compare different CSC-specific biomarkers that are present in various types of tumors. We further discuss multiple targeting approaches currently in preclinical or clinical testing that show great potential for targeting CSCs. This review discusses numerous strategies to eliminate CSCs by targeting surface biomarkers, regulating CSC-associated oncogenes and signaling pathways, inhibiting drug-efflux pumps involved in drug resistance, modulating the tumor microenvironment and immune system, and applying drug combination therapy using nanomedicine.

Extracellular matrix (ECM) is an essential component of the tumor microenvironment. Cancer development and progression are associated with increased ECM deposition and crosslink. The chemical and physical signals elicited from ECM are necessary for cancer cell proliferation and invasion. It is well recognized that stromal cells are a major source of ECM proteins. However, recent studies showed that cancer cells are also an active and important component in ECM remodeling. Cancer cells deposit a significant amount of collagen, fibronectin, and tenascin C (TNC). Recent studies demonstrate that these cancer cell-derived ECM proteins enhance cancer cell survival and promote cancer cell colonization at distant sites. ECM-related enzymes and chaperone proteins, such as prolyl-4-hydroxylase, lysyl-hydroxylase, lysyl oxidase, and heat shock protein 47, are also highly expressed in cancer cells. Inhibition of these enzymes significantly reduces cancer growth, invasion, and metastasis. These factors suggest that the cancer cell-derived ECM is crucial for cancer progression and metastasis. Therefore, targeting these ECM proteins and ECM-related enzymes is a potential strategy for cancer treatment.

The discovery of Toll-like receptors (TLRs) about 20 years ago was a remarkable achievement not only in the field of immunology but also in the field of medicine. The TLRs are a family of pattern recognition receptors which play an important role in immune responses by recognizing pathogen-associated molecular patterns. The TLRs also recognize danger-associated molecular patterns, which are associated with some diseases such as cancer. Recent evidence shows that TLRs are expressed not only in immune cells but also in tumor cells. The TLRs appear to play a role in tumor progression and treatment. Most likely, TLR activation has an impact on the initiation, development and treatment of tumors by modulating the inflammatory microenvironment. However, the activation of TLRs contributes to both inhibition and promotion of various tumors, with unclear underlying mechanisms. In this review article, the authors elucidate their current understanding about the role of TLRs in tumor progression, as well as the recent progress in utilizing TLR agonists as potential therapeutic agents in cancer treatment.

Worldwide, the incidence of primary brain tumors is on the rise. Unfortunately, noninvasive drug therapy is hampered by poor access of most drugs to the brain due to the insurmountable blood-brain barrier (BBB). Nanotechnology holds great promise for noninvasive therapy of severe brain diseases. Furthermore, recent bioconjugation strategies have enabled the invasion of the BBB via tailored-designed bioconjugates either with targeting moieties or alterations in the physicochemical and/or the pharmacokinetic parameters of central nervous system (CNS) active pharmaceutical ingredients. Multifunctional systems and new entities are being developed to target brain cells and tumor cells to resist the progression of brain tumors. Direct conjugation of an FDA-approved drug with a targeting moiety, diagnostic moiety, or pharmacokinetic-modifying moiety represents another current approach in combating brain tumors and metastases. Finally, genetic engineering, stem cells, and vaccinations are innovative nontraditional approaches described in different patents for the management of brain tumors and metastases. This review summarizes the recent technologies and patent applications in the past five years for the noninvasive treatment of glioblastoma and other brain tumors. Till now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are ongoing to bring novel CNS delivery systems to potential clinical application.

The knowledge that the body possesses natural defenses to combat cancer existed long before the modern period, with multiple anecdotal reports of tumors miraculously disappearing, sometimes spontaneously or after a febrile or infectious episode. Spontaneous tumor regression of untreated malignant tumors is currently a well-accepted albeit rare phenomenon, and it is recognized that immunosuppression is associated with a higher cancer risk. The treatment of bladder carcinoma by intravesical administration of live attenuated Bacillus Calmette-Guérin bacteria was shown to be very effective in 1976 and is now standard treatment. Effective immunity against cancer involves complex interactions between the tumor, the host, and the environment. Cancer immunotherapy uses various strategies to augment tumor immunity and represents a paradigm shift in treating cancer, since attention has become more focused on the “biologic passport” of the individual tumor rather than the site of origin of the tumor. The different types of cancer immunotherapies discussed here include biologic modifiers, such as cytokines and vaccines, adoptive cell therapies, oncolytic viruses, and antibodies against immune checkpoint inhibitors, such as the co-inhibitory T-cell receptor PD-1 and one of its ligands, programmed death-ligand 1.

Extracellular matrix (ECM) is an essential component of the tumor microenvironment. Cancer development and progression are associated with increased ECM deposition and crosslink. The chemical and physical signals elicited from ECM are necessary for cancer cell proliferation and invasion. It is well recognized that stromal cells are a major source of ECM proteins. However, recent studies showed that cancer cells are also an active and important component in ECM remodeling. Cancer cells deposit a significant amount of collagen, fibronectin, and tenascin C (TNC). Recent studies demonstrate that these cancer cell-derived ECM proteins enhance cancer cell survival and promote cancer cell colonization at distant sites. ECM-related enzymes and chaperone proteins, such as prolyl-4-hydroxylase, lysyl-hydroxylase, lysyl oxidase, and heat shock protein 47, are also highly expressed in cancer cells. Inhibition of these enzymes significantly reduces cancer growth, invasion, and metastasis. These factors suggest that the cancer cell-derived ECM is crucial for cancer progression and metastasis. Therefore, targeting these ECM proteins and ECM-related enzymes is a potential strategy for cancer treatment.

Aim: Estrogen receptor-α (ER-α) activation drives the progression of luminal breast cancers. Signaling by transforming growth factor-β (TGF-β) typically opposes the actions of ER-α; it also induces epithelial-mesenchymal transition (EMT) programs that promote breast cancer dissemination, stemness and chemoresistance. The impact of EMT programs on nongenomic ER-α signaling remains unknown and was studied herein.

Methods: MCF-7 and BT474 cells were stimulated with TGF-β to induce EMT programs, at which point ER-α expression, localization, and nongenomic interactions with receptor tyrosine kinases and MAP kinases (MAPKs) were determined. Cell sensitivity to anti-estrogens both before and after traversing the EMT program was also investigated.

Results: TGF-β-stimulated MCF-7 and BT474 cells to acquire EMT phenotypes, which enhanced cytoplasmic accumulation of ER-α without altering its expression. Post-EMT cells exhibited: (1) elevated expression of EGFR and IGF1R, which together with Src formed cytoplasmic complexes with ER-α; (2) enhanced coupling of EGF, IGF-1 and estrogen to the activation of MAPKs; and (3) reduced sensitivity to tamoxifen, an event reversed by administration of small molecule inhibitors against the receptors for TGF-β, EGF, and IGF-1, as well as those against MAPKs.

Conclusion: EMT stimulated by TGF-β promotes anti-estrogen resistance by activating EGFR-, IGF1R-, and MAPK-dependent nongenomic ER-α signaling.

Circulating tumor cells (CTCs) have become a blistering topic of discussion for oncologists because of their tremendous potential in the diagnosis and treatment of cancer. Over the past few years, they have been doled with quite an amount of research in this area understanding that CTCs are shed from tumors and circulate in the bloodstream. This process can also occur at an early stage of cancer. The major limitation in isolation of CTCs is their availability in limited numbers. Hence, many techniques have been developed and are under continuous improvement to enhance their efficacy of CTC isolation and enumeration. They have shown their potentiality to not just indicate the presence of a tumor but also to provide us with its core information. They have also proven to be useful in detecting minor subgroups of cells present in the primary tissue which might eventually be the cause of treatment resistance or relapse of the disease. Hence, detecting and characterizing CTCs can definitely become an inevitable step in treating solid tumor malignancies. In this review, we have tried to comprehend the basics of CTCs including isolation, detection, characterization, and molecular mechanism of their circulation in the blood stream. We have mostly focused on the significance of CTCs in diagnosis and therapies of four most common types of cancers, namely, breast, prostate, lung, and colorectal. This review provides the coverage of most of the advancements with regards to different tumor malignancies and their probable use in predicting outcomes of the disease to realize the concept of personalized medicine.

DNA damage is a vital challenge to cell homeostasis. Cellular responses to DNA damage (DDR) play essential roles in maintaining genomic stability and survival, whose failure could lead to detrimental consequences such as cancer development and aging. Nuclear factor-kappa B (NF-κB) is a family of transcription factors that plays critical roles in cellular stress response. Along with p53, NF-κB modulates transactivation of a large number of genes which participate in various cellular processes involved in DDR. Here the authors summarize the recent progress in understanding DNA damage response and NF-kB signaling pathways. This study particularly focuses on DNA damage-induced NF-κB signaling cascade and its physiological and pathological significance in B cell development and cancer therapeutic resistance. The authors also discuss promising strategies for selectively targeting this genotoxic NF-κB signaling aiming to antagonize acquired resistance and resensitize refractory cancer cells to cytotoxic treatments.

Cancer remains a worldwide health problem, being the disease with the highest impact on global health. Even with all the recent technological improvements, recurrence and metastasis still are the main cause of death. Since photodynamic therapy (PDT) does not compromise other treatment options and presents reduced long-term morbidity when compared with chemotherapy or radiotherapy, it appears as a promising alternative treatment for controlling malignant diseases. In this review, we set out to perform a broad up-date on PDT in cancer research and treatment, discussing how this approach has been applied and what it could add to breast cancer therapy. We covered topics going from the photochemical mechanisms involved, the different cell death mechanisms being triggered by a myriad of photosensitizers up to the more recent-on-going clinical trials.

For scientists pursuing drug development for prostate cancer, it is critical that an appropriate ex vivo or in vitro model system is available for study. Cancer research has generally consisted of: (1) finding the means to arrest fast growing cancer cells; or (2) (as a compromise) to slow down the excessive rate of cell growth; or in the best case (3) to kill the cancer cells whilst sparing the surrounding normal tissues. As the knowledge of the biological nature of the cancer cell improves, it has become increasingly apparent that such a simplistic attitude to cancer therapy development or indeed diagnosis is rapidly outdated, and a closer liaison between the clinic and the laboratory studies is more important than ever as the author seeks to target specific gene expression pathways, specific signaling pathways, cancer specific mutations and indeed the interactions between cancer cells and their micro-environment, all of which provide a tremendous potential for novel therapeutic development.

If the treatment landscape for prostate cancer is to be transformed, clinicians and scientists must work together ever more closely. Prostate cancer defeats physicians when patients are not accurately stratified according to patients’ risk of dying of disease, when the effects of tumor heterogeneity are insufficiently understood, and when attempts at therapy by clinicians spur further disease evolution and the emergence of new resistance mechanisms. At the same time, clinicians’ over-treat men who in reality do not need it, and some of those men needlessly suffer long term side effects as a result. This commentary is aimed at stimulating debate about how we as clinicians and scientists can assist one another and improve our knowledge to the benefit of patients dying from metastatic disease.

It is now well established that the tumor microenvironment plays an essential role in the survival, growth, invasion, and spread of cancer through the regulation of angiogenesis and localized immune responses. This review examines the role of the HOX genes, which encode a family of homeodomain-containing transcription factors, in the interaction between prostate tumors and their microenvironment. Previous studies have established that HOX genes have an important function in prostate cancer cell survival in vitro and in vivo, but there is also evidence that HOX proteins regulate the expression of genes in the cancer cell that influence the tumor microenvironment, and that cells in the microenvironment likewise express HOX genes that confer a tumor-supportive function. Here we provide an overview of these studies that, taken together, indicate that the HOX genes help mediate cross talk between prostate tumors and their microenvironment.

Researchers are currently trying to understand why some men with prostate cancer go on to develop aggressive disease whilst others maintain slow growing tumors. Although endogenous genetic anomalies within the tumor cell are important, the prevailing view is that the tissue microenvironment as a whole is the determinant factor. Many studies have focussed on the role of soluble factors in modulating the nature of the tumor microenvironment. There is however a growing interest in the role of extracellular vesicles, including exosomes, as regulators of disease progression. A variety of resident cells, as well as infiltrating cells, all contribute to a heterogeneous population of exosomes within the tumor microenvironment. Studies focussing on the role of exosomes in prostate cancer are however relatively rare. In this review, evidence from various cancers, including prostate, is used to present numerous potential roles of exosomes in prostate cancer. Whilst further validation of some functions may remain necessary it is clear that exosomes play a major role in intercellular communication between various cell types within the tumor microenvironment and are necessary for driving disease progression.

Aim: To develop new therapies for prostate cancer, disease heterogeneity must be addressed. This includes patient variation, multi-focal disease, cellular heterogeneity, genomic changes and epigenetic modification. This requires more representative models to be used in more innovative ways.

Methods: This study used a panel of cell lines and primary prostate epithelial cell cultures derived from patient tissue. Several assays were used; alamar blue, colony forming assays, γH2AX and Ki67 immunofluorescence and comet assays. Ptychographic quantitative phase imaging (QPI), a label-free imaging technique, combined with Cell Analysis Toolbox software, was implemented to carry out real-time analysis of cells and to retrieve morphological, kinetic and population data.

Results: A combination of radiation and Vorinostat may be more effective than radiation alone. Primary prostate cancer stem-like cells are more resistant to etoposide than more differentiated cells. Analysis of QPI images showed that cell lines and primary cells differ in their size, motility and proliferation rate. A QPI signature was developed in order to identify two subpopulations of cells within a heterogeneous primary culture.

Conclusion: Use of primary prostate epithelial cultures allows assessment of therapies whilst taking into account cellular heterogeneity. Analysis of rare cell populations and embracing novel techniques may ultimately lead to identifying and overcoming treatment resistance.

The membrane-type matrix metalloproteinases (MT-MMPs), an important subgroup of the wider MMP family, demonstrate widespread expression in multiple tumor types, and play key roles in cancer growth, migration, invasion and metastasis. Despite a large body of published research, relatively little information exists regarding evidence for MT-MMP expression and function in metastatic prostate cancer. This review provides an appraisal of the literature describing gene and protein expression in prostate cancer cells and clinical tissue, summarises the evidence for roles in prostate cancer progression, and examines the data relating to MT-MMP function in the development of bone metastases. Finally, the therapeutic potential of targeting MT-MMPs is considered. While MT-MMP inhibition presents a significant challenge, utilisation of MT-MMP expression and proteolytic capacity in prostate tumors is an attractive drug development opportunity.