Pluripotent Stem Cell–Based Cancer Therapy: Promise and Challenges

Induced pluripotent stem cells (iPSCs) are a new type of stem cell that is generated by reprogramming the genome of an adult somatic cell, such as a skin fibroblast, to a pluripotent state. Such iPSCs share many similarities with embryonic stem cells (ESCs). Reprogramming of adult somatic cells to iPSCs requires certain pluripotency factors, including the transcription factors Oct4, Sox2, and Klf4. These iPSCs are able to renew themselves indefinitely and to differentiate into many different cell types, including pancreatic-β cells, liver hepatocytes, cardiomyocytes, hematopoietic cells, and dopaminergic neurons. Consequently, there has been much enthusiasm about using iPSCs to generate tissues to treat a variety of diseases, including diabetes, liver cirrhosis, leukemia, and Parkinson’s disease, but ultimately how useful these cells will be for regenerative medicine is still not clear.

Fig. Roadblocks to translating human iPSC technology to the clinic.

Human iPSC technology potentially can be used for screening new cancer drugs (blue box) and ultimately for providing cells for transplant to treat a variety of diseases, including cancer (yellow box). Genetic mutations can be corrected in patient-derived iPSCs by gene targeting approaches. The main hurdles to using patient-specific iPSCs for disease modeling, drug screening, and transplantation purposes are (i) a lack of effective differentiation protocols, (ii) little or no engraftment capability for the majority of human iPSC-derived specialized cells, (iii) difficulties in modeling multifactorial diseases, (iv) the need for GMP-compliant conditions at each step, and (v) safety concerns regarding the potential tumorigenicity of iPSCs associated with their pluripotent state or with insertional- or culture-driven mutagenesis. Dotted arrow, not yet tested; solid arrow, only a few studies available; blue arrow, feasible but requires further study.

Cancer Stem Cell Therapy Market forecasts to 2026 detailed in new research report

This research holds critical and exclusive data to show the profound implications on the Cancer Stem Cell Therapy Market for the forecast period 2019 to 2026. Some of the main proponents of this hypothesis that the size, growth, and share of the Cancer Stem Cell Therapy industry is up for a major shift is compelling for business owners, stakeholders, field marketing executives and others trying to zero in on effective business strategies to gain maximum yield.

The market intelligence report blends in the best of both the primary and secondary research techniques to evaluate the project size of the Cancer Stem Cell Therapy industry across different countries. Apart from this, the study applies qualitative and quantitative study methods to identify the major outcomes of technology upgrades, joint ventures, collaborations, product launches and mergers and acquisitions worldwide.

Researchers have used self-explanatory tables, graphs and infographics to present data on customer preference, consumption volume, production capability, distribution channel and supply chain management.

Global Cancer Stem Cell Therapy Market: Type Segment Analysis (Consumption Volume, Average Price, Revenue, Market Share and Trend 2014-2026):

• Autologous Stem Cell Transplants
• Allogeneic Stem Cell Transplants
• Syngeneic Stem Cell Transplants
• Other

Global Cancer Stem Cell Therapy Market: Application Segment Analysis (Consumption Volume and Market Share 2014-2026; Downstream Customers and Market Analysis)

• Hospital
• Clinic
• Medical Research Institution
• Other

The expertise that has gone into this study is clearly visible from the way the subject matter experts have discussed the merger and acquisition opportunities in the report. Apart from identifying the local potential which can further assist in designing local market strategies the study brings to light the competitive scenario worldwide.

The study objectives of this report are:

• To analyze and study the global Cancer Stem Cell Therapy sales, value, status and forecast (2019-2026);
• To analyze the top players in North America, Europe, China, Japan, Southeast Asia and India, to study the sales, value and market share of top players in these regions.
• Focuses on the key Cancer Stem Cell Therapy players, to study the sales, value, market share and development plans in future.
• Focuses on the global key manufacturers, to define, describe and analyze the market competition landscape, SWOT analysis.
• To define, describe and forecast the market by type, application and region.

Treatment and Therapy: Cancer Nanotechnology

Cancer therapies are currently limited to surgery, radiation, and chemotherapy. All three methods risk damage to normal tissues or incomplete eradication of the cancer. Nanotechnology offers the means to target chemotherapies directly and selectively to cancerous cells and neoplasms, guide in surgical resection of tumors, and enhance the therapeutic efficacy of radiation-based and other current treatment modalities. All of this can add up to a decreased risk to the patient and an increased probability of survival.

Research on nanotechnology cancer therapy extends beyond drug delivery into the creation of new therapeutics available only through use of nanomaterial properties. Although small compared to cells, nanoparticles are large enough to encapsulate many small molecule compounds, which can be of multiple types. At the same time, the relatively large surface area of nanoparticle can be functionalized with ligands, including small molecules, DNA or RNA strands, peptides, aptamers or antibodies. These ligands can be used for therapeutic effect or to direct nanoparticle fate in vivo. These properties enable combination drug delivery, multi-modality treatment and combined therapeutic and diagnostic, known as “theranostic,” action. The physical properties of nanoparticles, such as energy absorption and re-radiation, can also be used to disrupt diseased tissue, as in laser ablation and hyperthermia applications.

Integrated development of innovative nanoparticle packages and active pharmaceutical ingredients will also enable exploration of a wider repertoire of active ingredients, no longer confined to those with acceptable pharmokinetic or biocompatibility behavior. In addition, immunogenic cargo and surface coatings are being investigated as both adjuvants to nanoparticle-mediated and traditional radio- and chemotherapy as well as stand-alone therapies. Innovative strategies include the design of nanoparticles as artificial antigen presenting cells and in vivo depots of immunostimulatory factors that exploit nanostructured architecture for sustained anti-tumor activity.

Brain cancer - Latest News, Latest Research | CANCERactive

LATEST NEWS AND RESEARCH ON BRAIN CANCER and BRAIN TUMOURS

Increase your personal odds of survival by empowering yourself with the latest news and research on brain cancer; news you can use today and incorporate into your integrative cancer treatment programme.

COVID-19 and immunomodulator/immunosuppressant use in dermatology

this time has been particularly concerning for patients taking immunomodulators/immunosuppressants who are unsure of their risk for severe disease.

In response to the previous commentary, the goal of this letter is to expand and provide the latest information about COVID-19 along with considerations for addressing patient concerns surrounding dermatology-related immunomodulator/immunosuppressant use.

Theoretical data from previous coronavirus outbreaks has suggested a strong role for type I interferon, B-cell–released antibodies, tumor necrosis factor-α, and other cytokines in the viral immune response. Interleukin (IL) 17 cytokines are important for immune cell recruitment to infection sites to promote clearance, while also activating downstream cascades of cytokines and chemokines. IL-1 promotes fever and the differentiation of T-helper cells to IL-17–producing T cells. Tumor necrosis factor-α promotes dendritic cell differentiation, leukocyte recruitment, and mediates fever. Antibodies produced by plasma cells help to neutralize the virus, limit infection, and prevent future infections. Disruption of B-cell differentiation into plasma cells could limit antibody production.

Mechanism:

COVID-19 viral immune response and targets of common dermatologic immunomodulators and immunosuppressants. (Left) (1) Person-to-person transmission of COVID-19 occurs though direct contact with respiratory secretions of infected individuals.2 The virus invades host cells by binding to their receptors and fusing with the cell membrane. (2) It is hypothesized that once inside the body, the lung epithelial cells become the primary target, where the receptor binding domain of the virus spikes bind to angiotensin-converting enzyme 2 (ACE2) receptors of ACE2-expressing target cells. (3) Although not confirmed, it is believed the virus dampens the initial type 1 interferon (IFN) responses, which contributes to uncontrolled viral replication. (4) Once the virus is identified, macrophages present viral components to activate and induce (5) differentiation of T cells and B cells. (6) Activated B cells differentiate into plasma cells that produce antibodies important for neutralizing viruses. (7) The resulting inflammatory cytokines and antibodies continue to stimulate the production of additional cytokines and antibodies, which may contribute to the “cytokine storm” noted in those with severe disease. (8) The inflammatory cytokines and antibodies also promote the influx of neutrophils, monocytes, and macrophages along with additional inflammatory cytokines. (Right) The drug targets for common dermatologic immunomodulators and immunosuppressants have also been included in this diagram. FGF, Basic fibroblast growth factor; GCSF, granulocyte-colony stimulating factor; GMCSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; IP10, interferon γ-induced protein 10; IRF, interferon regulatory factor; MCP1, monocyte chemoattractant protein 1; MIP1A, macrophage inflammatory protein 1-α; NFAT, nuclear factor of activated T cells; NF-κB, nuclear factor-κB; PDE4, phosphodiesterase 4; PDGF, platelet-derived growth factor; PKA, protein kinase A; TH, T-helper cell; TNF, tumor necrosis factor; VEGFA, vascular endothelial growth factor A.

Medical Breakthrough!! Lastest Research in Cancer Treatment

Scientists have moved one step closer to developing a capsule that can potentially alter the treatment paradigm from painful intravenous injections currently used to treat an advanced form of cancers such as melanoma, lung cancer, and advanced renal cell carcinoma.

Checkpoint inhibitors or the mechanism of blocking proteins that are expressed on cancer cells or immune cells in the human body and trigger the body’s immune system to fight cancer cells is the latest frontier in cancer research with large drug makers pumping in billions of dollars in search of effective leads.

RNA-based cancer vaccines

Development of personalized RNA-based cancer vaccines. Tumor samples are subjected to whole genome sequencing and genetic mutations related to immunogenic feature will be screened out for the design of RNA-based vaccines. RNAs encoding for unique tumor antigens could be either injected to human body or transfected into DCs to develop cell surface antigens. RNAs will express antigenic protein in the APCs and present specific antigens through MHC I and MHC II. Presentation of antigens by APCs will promote the interactions between APCs and immune system cells, through the interactions of antigens and T cell receptors. This interaction will trigger a series of downstream immune responses.  

Eat Anti-Cancer Foods Every Day For Maximum Benefit

Diet and lifestyle changes may account for as much as 68% of all cancers, with dietary causes alone accounting for 20-40% of cancers.

Nutrition therapy is a key part of many cancer approaches these days, and can also help reduce the side effects of conventional cancer treatments.

So what you put in your mouth three times a day can make a big difference to your health, including your ability to prevent and heal cancer.

Defining the unique genetic characteristics of brain tumors may lead to better diagnosis and therapy

Brain cancer—the very words evoke fear. And for good reason. Despite advancements in the detection and treatment of other tumor types, brain cancer continues to be one of the deadliest forms of the disease. But thanks to technological advances and scientific breakthroughs, the field is ripe for progress. That's why, roughly five years ago, neuro-oncologists at the School of Medicine joined forces to tackle this most formidable of cancer frontiers. Today, their multidisciplinary approach incorporates a wide range of clinical and laboratory expertise.

8 Ways To Prevent Cancer

Our researchers are sharing the latest discoveries in cancer prevention research that will lower a person’s risk of developing cancer.

Fruits, vegetables, 'farm-to-fork continuum' vital to cancer prevention

Instead, research should shift toward developing prevention strategies for cancer. Accumulating evidence suggests that a diet high in plant-based foods is preventive of a variety of chronic diseases, including cancer. A plethora of bioactive compounds -- such as polyphenols, glucosinolates and carotenoids in fruits, vegetables, grains and legumes -- are shown to suppress a variety of biological capabilities required for tumor growth.

While much research has shown that plant bioactive compounds can suppress cancer growth and promote the demise of certain cancer cells, public health campaigns to increase fruit and vegetable consumption have been less effective than desired. In his article, "Food Systems Approach to Cancer Prevention," (which appeared in the journal Food Science and Nutrition), calls for innovative strategies to support increased consumption of bioactive compounds for cancer prevention.

"Many practices in the farm-to-fork continuum, including preharvest methods, postharvest storage and processing, and consumer practices, affect a food's bioactive compound content, composition and chemopreventive bioactivity," Vanamala explained. "Food system practices may be adjusted to improve the bioactive compound profile, elevating the cancer-fighting properties of fruits, vegetables and other food products."

Ultimately, more systematic study of farm-to-fork effects on bioactive compounds will allow a greater understanding of the role of food in cancer prevention and will provide valuable information for use in many applications. More detailed research into how different farm-to-fork operations affect bioactive compounds could allow for strategic food system reform aimed at increasing the delivery of bioactive compounds and decreasing cancer incidence.

Diet And Cancer

Our food includes different types of nutrients, vitamins and other things (food additives). Some of these protect us against cancers where as others increase the risk. Knowing that dietary factors also play a significant role in cancer risk, it is important to know whether the food we are eating nourishes our body, protects us from disease or is harmful to us.

• Insoluble grain fiber in coarse grains (e.g., rye, sorghum, maize, barley and millets).
• Micronutrients like vitamins and trace elements.
• Vitamins A, E, and trace minerals such as selenium, zinc.
• Vitamin-D and calcium are also found to give protection against colorectal cancer.
• Green tea and its compounds.

• Retinoids (found in orange and red vegetables and fruits like sweet potatoes, mangoes, pumpkins, peaches and carrots) have been found to inhibit cancer growth in epithelial tissues.
• 13-Cis-Retinoic acid is used in the treatment of skin and cervical cancers.
• High intake of Beta-Carotene rich foods decrease the incidence of esophageal cancer.

National Institute of Nutrition (NIN) recommends a diet (min 400gm) that includes high intake of fresh vegetables, fruits, garlic and spices such as turmeric in adequate amounts for cancer prevention.

Diet and Specific Cancers

Cervical Cancer

A diet high in carotenoids, vegetables, and fruits may reduce the risk of cervical, ovarian, and endometrial cancers.

High intake of vitamins C and E may reduce the risk of cervical cancer.

Breast Cancer

Intake of more of saturated fats and obesity have been linked to breast cancer.

The nutrition guidelines and the World Cancer Research Fund recommendations advocate that having a diet with liberal amount of vegetables and fruits, less of saturated fats decreases that risk of breast cancer.

Oral Cancer

Increased consumption of fish, eggs, raw and cooked vegetables, and fruit is associated with a decreased risk of oral cancer.

This #Quarantine & #Lockdown helps everyone to get #attentiveness on their #health stay #fit & #Safe And do #support us by sharing your ideas on #oncology #Cancer in our online conference #2020oncology with your valuable talks Visit the link: oncology.euroscicon for more info

New Therapeutic Trial Designs in Personalized Medicine: Cancer Prevention and Cancer Genetics

The Cancer Prevention and Cancer Genetics group studies novel cancer therapies and cancer prevention strategies. Group members are involved in epidemiological, laboratory and clinical studies to examine the factors that contribute to the development and progression of tumours.

Highlights in nanocarriers for the treatment against cervical cancer

In an in ideal scenario of cancer treatment, the early phase of this transformation journey is detected noninvasively in routine checks through imaging and analysis, targeted drugs are delivered at the specific sites selectively with minimal collateral damage by carriers that overcome biological barriers, and the transforming population of cells are eliminated (Ferrari, 2005). Such treatment can be repeated based on individualized needs. This envisioned treatment scenario is still far in the future, but several applications of nanotechnology in cancer treatment are showing signs of promise of transforming this vision into reality.

Nanotechnology: Cancer and Treatment

In an in ideal scenario of cancer treatment, the early phase of this transformation journey is detected noninvasively in routine checks through imaging and analysis, targeted drugs are delivered at the specific sites selectively with minimal collateral damage by carriers that overcome biological barriers, and the transforming population of cells are eliminated (Ferrari, 2005). Such treatment can be repeated based on individualized needs. This envisioned treatment scenario is still far in the future, but several applications of nanotechnology in cancer treatment are showing signs of promise of transforming this vision into reality.

Systemic Therapy for Metastatic Renal-Cell Carcinoma

Kidney cancers have been extensively studied, and insights from an increased understanding of tumor biology have led to increases in survival rates. Therapies aimed at tumor signaling pathways and immunotherapies have improved the outlook for patients with renal cancer.

Targeting cancer stem cell pathways for cancer therapy

Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.

Targeting of Cancer stem cells

Targeting of cancer stem cells. Depletion of cancer stem cells is of the utmost importance to successful cancer treatment. As CSC survive conventional therapy, significant tumor shrinkage is achieved, but the repopulation capacity of CSC will eventually lead to tumor relapse. Targeted anti-stem cell therapy, however, should eliminate CSC and thus the root of the tumor, which will then degenerate over time. 

Webinar: Oncology 2020

Normal Stem Cells and Cancer Stem Cells: The Niche Matters

Scientists have tried for decades to understand cancer development in the context of therapeutic strategies. The realization that cancers may rely on “cancer stem cells” that share the self-renewal feature of normal stem cells has changed the perspective with regard to new approaches for treating the disease. In this review, we propose that one of the differences between normal stem cells and cancer stem cells is their degree of dependence on the stem cell niche, a specialized microenvironment in which stem cells reside. The stem cell niche in adult somatic tissues plays an essential role in maintaining stem cells or preventing tumorigenesis by providing primarily inhibitory signals for both proliferation and differentiation. However, the niche also provides transient signals for stem cell division to support ongoing tissue regeneration. The balance between proliferation-inhibiting and proliferation-promoting signals is the key to homeostatic regulation of stem cell maintenance versus tissue regeneration. Loss of the niche can lead to loss of stem cells, indicating the reliance of stem cells on niche signals. Therefore, cancer stem cells may arise from an intrinsic mutation, leading to self-sufficient cell proliferation, and/or may also involve deregulation or alteration of the niche by dominant proliferation-promoting signals. Furthermore, the molecular machinery used by normal stem cells for homing to or mobilizing from the niche may be “hijacked” by cancer stem cells for invasion and metastasis. We hope this examination of the interaction between stem cells and their niche will enhance understanding of the process of cancer development, invasiveness, and metastasis and reveal possible targets for cancer treatment.

On the trail of cancer stem cells

Two research teams from the Max Delbrück Center for Molecular Medicine and their collaborators have produced a detailed cell atlas of an entire salivary gland tumor in a mouse model, mapping individual cells throughout the tumor and its surrounding tissue. The "single cell" approach, recently described in Nature Communications, has provided key insights about cellular composition changes through the earliest stages of cancer development.

A solid tumor is not, as many might assume, a lump of cells that are all the same. Rather it is mix of many different cell types, including a variety of stromal and immune cells besides the actual tumor cells.

Further research is required to verify that individual cells are transforming through these stages, and explore the cellular and molecular interactions driving tumor growth. The team anticipates the approach they've demonstrated here can be applied to other cancer types as well.

Tumor immunity

Cancer immunotherapy is a new and extremely exciting option for cancer treatment. Cancer immunotherapy functions by using the patient’s own immunity to attack the cancer cells. In many cases, however, it has been reported that immune cells are deemed to be suppressed in the tumors. In fact, anti-PD-1 antibody, which resuscitates dysfunctioned cytotoxic-T lymphocytes against cancer antigens, has been validated as an anti-tumor drug recently. Other than PD-1, immunosuppressive cells such as regulatory T cells (Tregs), myeloid-derived suppressor-cells (MDSCs), Tumor-associated macrophages (TAMs) are suspected for pivotal factors against anti-tumor immunity. Our lab is researching the mechanisms responsible for this immune suppression in tumors by examining patient’s tissue and blood. Normally, these samples are small, but we have been optimizing methods and analysis to study the above immune cells extracted from the tumors. Our goal is to understand the mechanism of tumor immune regulation for the development of new immunotherapy strategies and targets.

Therapeutic vaccines and immune checkpoints inhibition options for gynecological cancers

Treatments for gynecological cancer include surgery, chemotherapy, and radiation. However, overall survival is not improved, and novel approaches are needed. Immunotherapy has been proven efficacious in various types of cancers and multiple approaches have been recently developed.

Research Areas

Personalized or precision medicine necessitates a comprehensive and integrated approach to mechanisms underlying drug action. While pursuing new initiatives in Clinical and Translational Sciences, Pharmacogenomics, Systems Approaches, Medicinal Chemistry and Drug Discovery, the Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) continues to build in its core areas of Pharmaceutical Biotechnology, Biophysics, Toxicology and Cancer Pharmacology, as well as in Pharmaceutical Outcomes Research and multiple clinical specialties.

Pharmaceutical Biotechnology. With its roots in classical pharmaceutics, Pharmaceutical Biotechnology focuses on newer macromolecular pharmaceuticals such as proteins and nucleic acids. Especially relevant for vaccines and therapeutic antibodies, this area of study focuses on stability, formulation and targeted delivery. With co-directors from both the Department of Pharmaceutical Sciences and the Department of Chemical Engineering at the University of Colorado Boulder, the Center for Pharmaceutical Biotechnology is recognized for its innovative research, excellence in PhD education and annual conferences attracting scientists from around the globe.

Molecular Biophysics explores the thermodynamic and kinetic mechanisms responsible for biological regulation. Areas of emphasis include analysis of transcription factor-gene promoter interactions; characterization of viral assembly and DNA packaging; and studies of protein stability and misfolding in human diseases.

Molecular Toxicology focuses on elucidation of molecular mechanisms of toxicity of drugs and pollutants, and includes metabolic, pharmacogenomics, proteomic and metabolomics approaches. These techniques allow studies of individual susceptibility and isolation of predictive biomarkers of toxicity.

Cancer Pharmacology focuses on signaling mechanisms critical in obtaining the desired response associated with chemotherapy and cancer prevention. Areas of emphasis include chemoprevention by natural products.

Clinical and Translational Sciences examines the importance of pharmacokinetics, pharmacodynamics and pharmacogenetics that influence clinical response. The Center for Translational Pharmacokinetics and Pharmacogenomics was developed to provide a focus in this area of clinical pharmacology for investigators across the campus and region.

Drug Discovery. Areas of focus include structure based drug design, computational modeling of drug-target interactions and natural product chemistry. The medicinal chemistry focus is supported by three integrated drug discovery catalyst facilities:

The Computational Chemistry and Biochemistry catalyst facility provides molecular docking studies, pharmacophore modeling, ligand design, virtual screening of compound libraries and computational modeling of protein-protein interactions. The Medicinal Chemistry catalyst facility performs synthesis, analysis, metabolic studies and assistance in lead compound optimization. The High Throughput Screening (HTS) catalyst facility performs validation of screens for applications and screening of compound libraries against potential therapeutic targets.

Systems Approaches. Since many of the research applications employed today require the use of combined omic approaches, the department operates a Mass Spectrometry core facility, which provides analytical resources for metabolomics, proteomic and small molecule analysis. These resources facilitate biomarker analysis and allow complete analysis of metabolomics and proteomic changes associated with drugs and toxicants. Bioinformatic approaches and studies of the microbiome allow an integrated systems approach to mechanisms of drug action.

Nanomedicine and Nanosafety. A critical mass of investigators exploit nanoparticles for targeted drug delivery and imaging. Nanoparticles can also induce immune mediated effects and other toxicities so the Colorado Center for Nanomedicine and Nanosafety was established to provide a focus for nano-based research in the state.

Pharmaceutical Outcomes Research is one area of expertise in the Department of Clinical Pharmacy and is led by faculty in the Center for Pharmaceutical Outcomes Research. The center has also been recently developed to provide a focus for outcomes research activities in the state.

Highlights in nanocarriers for the treatment against cervical cancer

Nanotechnology application in the treatment of cancer: tumor targeting of long-circulating polymer therapeutics occurs passively by the enhanced permeability and retention (EPR) effect. Tumor vasculature allows preferential extravasation of circulating nanocarriers. Once present in the tumor interstitium, nanocarriers act either after endocytic internalization or extracellularly. 

New direction urged to improve cancer nanotechnology

Researchers involved in a national effort to develop cancer treatments that harness nanotechnology are recommending pivotal changes in the field because experiments with laboratory animals and efforts based on current assumptions about drug delivery have largely failed to translate into successful clinical results.

The assessment was advanced in a perspective piece that appeared in the National Cancer Institute's "Cancer Nanotechnology Plan 2015", a 10-year roadmap concerning the use of nanotechnology to attack cancer.

Researchers are trying to perfect "targeted delivery" methods using various agents, including an assortment of tiny nanometer-size structures, to selectively attack tumor tissue. However, the current direction of research has brought only limited progress, according to the authors of the article.

One approach pursued by researchers has been to design nanoparticles small enough to pass through pores in blood vessels surrounding tumors but too large to pass though the pores of vessels in healthy tissue. The endothelial cells that make up healthy blood vessels are well organized with tight junctions between them. However, the endothelial cells in blood vessels around tumors are irregular and misshapen, with loose gaps between the cells.

"We should realize that having a specific nanosize or functionality alone is not enough to guarantee good drug delivery to target tumors," said Kinam Park, a professor of pharmaceutics and Purdue's Showalter Distinguished Professor of Biomedical Engineering. "The tumor microenvironment is just too complex to overcome using this strategy alone."

Cancer Nanotechnology: Treatment and Therapy

Cancer therapies are currently limited to surgery, radiation, and chemotherapy. All three methods risk damage to normal tissues or incomplete eradication of the cancer. Nanotechnology offers the means to target chemotherapies directly and selectively to cancerous cells and neoplasms, guide in surgical resection of tumors, and enhance the therapeutic efficacy of radiation-based and other current treatment modalities. All of this can add up to a decreased risk to the patient and an increased probability of survival.

Research on nanotechnology cancer therapy extends beyond drug delivery into the creation of new therapeutics available only through use of nanomaterial properties. Although small compared to cells, nanoparticles are large enough to encapsulate many small molecule compounds, which can be of multiple types. At the same time, the relatively large surface area of nanoparticle can be functionalized with ligands, including small molecules, DNA or RNA strands, peptides, aptamers or antibodies. These ligands can be used for therapeutic effect or to direct nanoparticle fate in vivo. These properties enable combination drug delivery, multi-modality treatment and combined therapeutic and diagnostic, known as “theranostic,” action. The physical properties of nanoparticles, such as energy absorption and re-radiation, can also be used to disrupt diseased tissue, as in laser ablation and hyperthermia applications.

Integrated development of innovative nanoparticle packages and active pharmaceutical ingredients will also enable exploration of a wider repertoire of active ingredients, no longer confined to those with acceptable pharmokinetic or biocompatibility behavior. In addition, immunogenic cargo and surface coatings are being investigated as both adjuvants to nanoparticle-mediated and traditional radio- and chemotherapy as well as stand-alone therapies. Innovative strategies include the design of nanoparticles as artificial antigen presenting cells and in vivo depots of immunostimulatory factors that exploit nanostructured architecture for sustained anti-tumor activity.

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