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European Journal of Pharmaceutics and... Jun 2015Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell... (Review)
Review
Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vascularization and, in time, acquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastatic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, such as the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic drugs, as well as the development of multidrug resistance, support the need to find new effective targeted treatments based on the changes in the molecular biology of the tumor cells. These novel targeted therapies, of increasing interest as evidenced by FDA-approved targeted cancer drugs in recent years, block biologic transduction pathways and/or specific cancer proteins to induce the death of cancer cells by means of apoptosis and stimulation of the immune system, or specifically deliver chemotherapeutic agents to cancer cells, minimizing the undesirable side effects. Although targeted therapies can be achieved directly by altering specific cell signaling by means of monoclonal antibodies or small molecules inhibitors, this review focuses on indirect targeted approaches that mainly deliver chemotherapeutic agents to molecular targets overexpressed on the surface of tumor cells. In particular, we offer a detailed description of different cytotoxic drug carriers, such as liposomes, carbon nanotubes, dendrimers, polymeric micelles, polymeric conjugates and polymeric nanoparticles, in passive and active targeted cancer therapy, by enhancing the permeability and retention or by the functionalization of the surface of the carriers, respectively, emphasizing those that have received FDA approval or are part of the most important clinical studies up to date. These drug carriers not only transport the chemotherapeutic agents to tumors, avoiding normal tissues and reducing toxicity in the rest of the body, but also protect cytotoxic drugs from degradation, increase the half-life, payload and solubility of cytotoxic agents and reduce renal clearance. Despite the many advantages of all the anticancer drug carriers analyzed, only a few of them have reached the FDA approval, in particular, two polymer-protein conjugates, five liposomal formulations and one polymeric nanoparticle are available in the market, in contrast to the sixteen FDA approval of monoclonal antibodies. However, there are numerous clinical trials in progress of polymer-protein and polymer-drug conjugates, liposomal formulations, including immunoliposomes, polymeric micelles and polymeric nanoparticles. Regarding carbon nanotubes or dendrimers, there are no FDA approvals or clinical trials in process up to date due to their unresolved toxicity. Moreover, we analyze in detail the more promising and advanced preclinical studies of the particular case of polymeric nanoparticles as carriers of different cytotoxic agents to active and passive tumor targeting published in the last 5 years, since they have a huge potential in cancer therapy, being one of the most widely studied nano-platforms in this field in the last years. The interest that these formulations have recently achieved is stressed by the fact that 90% of the papers based on cancer therapeutics with polymeric nanoparticles have been published in the last 6 years (PubMed search).
Topics: Animals; Antineoplastic Agents; Chemistry, Pharmaceutical; Diffusion of Innovation; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Forecasting; Humans; Medical Oncology; Nanomedicine; Nanoparticles; Neoplasms; Technology, Pharmaceutical; Treatment Outcome
PubMed: 25813885
DOI: 10.1016/j.ejpb.2015.03.018 -
International Journal of Molecular... Mar 2021Gastric cancer's bad incidence, prognosis, cellular and molecular heterogeneity amongst others make this disease a major health issue worldwide. Understanding this... (Review)
Review
Gastric cancer's bad incidence, prognosis, cellular and molecular heterogeneity amongst others make this disease a major health issue worldwide. Understanding this affliction is a priority for proper patients' management and for the development of efficient therapeutical strategies. This review gives an overview of major scientific advances, made during the past 5-years, to improve the comprehension of gastric adenocarcinoma. A focus was made on the different actors of gastric carcinogenesis, including, cancer stem cells, tumour microenvironment and microbiota. New and recent potential biomarkers were assessed as well as emerging therapeutical strategies involving cancer stem cells targeting as well as immunotherapy. Finally, recent experimental models to study this highly complex disease were discussed, highlighting the importance of gastric cancer understanding in the hard-fought struggle against cancer relapse, metastasis and bad prognosis.
Topics: Adenocarcinoma; Animals; Biomarkers; Biomarkers, Tumor; Carcinogenesis; Cell Line, Tumor; Helicobacter Infections; Helicobacter pylori; Humans; Immunotherapy; Liquid Biopsy; Mice; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplastic Stem Cells; Prognosis; Recurrence; Risk Factors; Stomach Neoplasms; Tumor Microenvironment
PubMed: 33810350
DOI: 10.3390/ijms22073418 -
International Journal of Molecular... Feb 2021Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant... (Review)
Review
Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant therapeutic modalities in oncology. Antibody-drug conjugates, bispecific antibodies, peptides, cell, and gene-therapies are emerging to address the unmet patient need. Advancement in the discovery and development platforms, identification of novel targets, and emergence of new technologies have greatly expanded the treatment options for patients. Here, we provide an overview of various therapeutic modalities and the current treatment options in oncology, and an in-depth discussion of the therapeutics in the preclinical stage for the treatment of breast cancer, lung cancer, and multiple myeloma.
Topics: Antibodies, Monoclonal; Cell- and Tissue-Based Therapy; Genetic Therapy; Humans; Immunoconjugates; Immunotherapy; Medical Oncology; Molecular Targeted Therapy; Neoplasms; Small Molecule Libraries
PubMed: 33670524
DOI: 10.3390/ijms22042008 -
Nature Reviews. Cancer Nov 2022Historically, the primary focus of cancer research has been molecular and clinical studies of a few essential pathways and genes. Recent years have seen the rapid... (Review)
Review
Historically, the primary focus of cancer research has been molecular and clinical studies of a few essential pathways and genes. Recent years have seen the rapid accumulation of large-scale cancer omics data catalysed by breakthroughs in high-throughput technologies. This fast data growth has given rise to an evolving concept of 'big data' in cancer, whose analysis demands large computational resources and can potentially bring novel insights into essential questions. Indeed, the combination of big data, bioinformatics and artificial intelligence has led to notable advances in our basic understanding of cancer biology and to translational advancements. Further advances will require a concerted effort among data scientists, clinicians, biologists and policymakers. Here, we review the current state of the art and future challenges for harnessing big data to advance cancer research and treatment.
Topics: Humans; Artificial Intelligence; Computational Biology; Proteomics; Translational Research, Biomedical; Biomedical Research; Neoplasms
PubMed: 36064595
DOI: 10.1038/s41568-022-00502-0 -
The Lancet. Oncology Aug 2017The lifestyle factors of physical activity, sedentary behaviour, and diet are increasingly being studied for their associations with cancer. Physical activity is... (Review)
Review
The lifestyle factors of physical activity, sedentary behaviour, and diet are increasingly being studied for their associations with cancer. Physical activity is inversely associated with and sedentary behaviour is positively (and independently) associated with an increased risk of more than ten types of cancer, including colorectal cancer (and advanced adenomas), endometrial cancers, and breast cancer. The most consistent dietary risk factor for premalignant and invasive breast cancer is alcohol, whether consumed during early or late adult life, even at low levels. Epidemiological studies show that the inclusion of wholegrain, fibre, fruits, and vegetables within diets are associated with reduced cancer risk, with diet during early life (age <8 years) having the strongest apparent association with cancer incidence. However, randomised controlled trials of diet-related factors have not yet shown any conclusive associations between diet and cancer incidence. Obesity is a key contributory factor associated with cancer risk and mortality, including in dose-response associations in endometrial and post-menopausal breast cancer, and in degree and duration of fatty liver disease-related hepatocellular carcinoma. Obesity produces an inflammatory state, characterised by macrophages clustered around enlarged hypertrophied, dead, and dying adipocytes, forming crown-like structures. Increased concentrations of aromatase and interleukin 6 in inflamed breast tissue and an increased number of macrophages, compared with healthy tissue, are also observed in women with normal body mass index, suggesting a metabolic obesity state. Emerging randomised controlled trials of physical activity and dietary factors and mechanistic studies of immunity, inflammation, extracellular matrix mechanics, epigenetic or transcriptional regulation, protein translation, circadian disruption, and interactions of the multibiome with lifestyle factors will be crucial to advance this field.
Topics: Breast Neoplasms; Colorectal Neoplasms; Diet; Exercise; Female; Health Behavior; Humans; Incidence; Liver Neoplasms; Male; Neoplasms; Obesity; Pancreatic Neoplasms; Prostatic Neoplasms; Risk Factors; Sedentary Behavior
PubMed: 28759385
DOI: 10.1016/S1470-2045(17)30411-4 -
Nature Reviews. Clinical Oncology Jun 2018The combination of next-generation sequencing and advanced computational data analysis approaches has revolutionized our understanding of the genomic underpinnings of... (Review)
Review
The combination of next-generation sequencing and advanced computational data analysis approaches has revolutionized our understanding of the genomic underpinnings of cancer development and progression. The coincident development of targeted small molecule and antibody-based therapies that target a cancer's genomic dependencies has fuelled the transition of genomic assays into clinical use in patients with cancer. Beyond the identification of individual targetable alterations, genomic methods can gauge mutational load, which might predict a therapeutic response to immune-checkpoint inhibitors or identify cancer-specific proteins that inform the design of personalized anticancer vaccines. Emerging clinical applications of cancer genomics include monitoring treatment responses and characterizing mechanisms of resistance. The increasing relevance of genomics to clinical cancer care also highlights several considerable challenges, including the need to promote equal access to genomic testing.
Topics: Cancer Vaccines; Disease Progression; Drug Resistance, Neoplasm; Genome, Human; Genomics; High-Throughput Nucleotide Sequencing; Humans; Mutation; Neoplasms; Precision Medicine
PubMed: 29599476
DOI: 10.1038/s41571-018-0002-6 -
Pathology Oncology Research : POR Apr 2017With the advancement and improvement of new sequencing technology, next-generation sequencing (NGS) has been applied increasingly in cancer genomics research fields.... (Review)
Review
With the advancement and improvement of new sequencing technology, next-generation sequencing (NGS) has been applied increasingly in cancer genomics research fields. More recently, NGS has been adopted in clinical oncology to advance personalized treatment of cancer. NGS is utilized to novel diagnostic and rare cancer mutations, detection of translocations, inversions, insertions and deletions, detection of copy number variants, detect familial cancer mutation carriers, provide the molecular rationale for appropriate targeted, therapeutic and prognostic. NGS holds many advantages, such as the ability to fully sequence all types of mutations for a large number of genes (hundreds to thousands) and the sensitivity, speed in a single test at a relatively low cost compared to be other sequencing modalities. Here we described the technology, methods and applications that can be immediately considered and some of the challenges that lie ahead.
Topics: Genomics; High-Throughput Nucleotide Sequencing; Humans; Mutation; Neoplasms; Sequence Analysis, DNA
PubMed: 27722982
DOI: 10.1007/s12253-016-0124-z -
Medicine Jan 2024Breast cancer remains a complex and prevalent health concern affecting millions of individuals worldwide. This review paper presents a comprehensive analysis of the... (Review)
Review
Breast cancer remains a complex and prevalent health concern affecting millions of individuals worldwide. This review paper presents a comprehensive analysis of the multifaceted landscape of breast cancer, elucidating the diverse spectrum of risk factors contributing to its occurrence and exploring advancements in diagnostic methodologies. Through an extensive examination of current literature, various risk factors have been identified, encompassing genetic predispositions such as BRCA mutations, hormonal influences, lifestyle factors, and reproductive patterns. Age, family history, and environmental factors further contribute to the intricate tapestry of breast cancer etiology. Moreover, this review delineates the pivotal role of diagnostic tools in the early detection and management of breast cancer. Mammography, the cornerstone of breast cancer screening, is augmented by emerging technologies like magnetic resonance imaging and molecular testing, enabling improved sensitivity and specificity in diagnosing breast malignancies. Despite these advancements, challenges persist in ensuring widespread accessibility to screening programs, particularly in resource-limited settings. In conclusion, this review underscores the importance of understanding diverse risk factors in the development of breast cancer and emphasizes the critical role of evolving diagnostic modalities in enhancing early detection. The synthesis of current knowledge in this review aims to contribute to a deeper comprehension of breast cancer's multifactorial nature and inform future directions in research, screening strategies, and preventive interventions.
Topics: Humans; Female; Breast Neoplasms; Early Detection of Cancer; Mammography; Breast; Risk Factors
PubMed: 38241592
DOI: 10.1097/MD.0000000000036905 -
Genes & Development May 2006Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a median survival of <6 mo and a dismal 5-yr survival rate... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a median survival of <6 mo and a dismal 5-yr survival rate of 3%-5%. The cancer's lethal nature stems from its propensity to rapidly disseminate to the lymphatic system and distant organs. This aggressive biology and resistance to conventional and targeted therapeutic agents leads to a typical clinical presentation of incurable disease at the time of diagnosis. The well-defined serial histopathologic picture and accompanying molecular profiles of PDAC and its precursor lesions have provided the framework for emerging basic and translational research. Recent advances include insights into the cancer's cellular origins, high-resolution genomic profiles pointing to potential new therapeutic targets, and refined mouse models reflecting both the genetics and histopathologic evolution of human PDAC. This confluence of developments offers the opportunity for accelerated discovery and the future promise of improved treatment.
Topics: Animals; Carcinoma, Pancreatic Ductal; Disease Models, Animal; Humans; Mice; Mice, Mutant Strains; Pancreas; Pancreatic Neoplasms
PubMed: 16702400
DOI: 10.1101/gad.1415606 -
Seminars in Cancer Biology Oct 2018Recent large scale genomic studies from the Clinical Lung Cancer Genome Project have identified different driver gene mutations in the subtypes of non-small cell lung... (Review)
Review
Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy.
Recent large scale genomic studies from the Clinical Lung Cancer Genome Project have identified different driver gene mutations in the subtypes of non-small cell lung carcinoma (NSCLC). These findings not only lead to remarkable progress in targeted therapies for lung cancer patients, but also provide fundamental knowledge for the subclassification of NSCLC. More recently, the advancement and clinical application of immunotherapy have reinforced the need for the accurate subclassification of NSCLC. In 2015, the World Health Organization (WHO) and the International Association for the Study of Lung Cancer (IASLC) updated their guidelines for the subclassification of lung cancers. These guidelines emphasize: (1) the subclassification of NSCLC, (2) the critical role of molecular characterization of tumors for targeted therapy, (3) the unique terminology for subclassifying NSCLC using small biopsy specimens, and (4) the utility of IHC biomarkers in the accurate diagnosis and subclassification of lung cancer. The guidelines have significant prognostic impact on oncologic practice and patient care. In this review, we summarize the current WHO guidelines for the classification of lung cancer, discuss advancements of targeted therapy and immunotherapy, and address the utility and limitation of immunomarkers in the subclassification of NSCLC, as well as the prospective future of the field.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Humans; Immunohistochemistry; Immunotherapy; Lung Neoplasms; Molecular Targeted Therapy; Practice Guidelines as Topic; World Health Organization
PubMed: 29183778
DOI: 10.1016/j.semcancer.2017.11.019