Smart Nanoparticles for Chemo-Based Combinational Therapy

Cancer is a heterogeneous and complex disease. Traditional cancer therapy is associated with low therapeutic index, acquired resistance, and various adverse effects. With the increasing understanding of cancer biology and technology advancements, more strategies have been exploited to optimize the therapeutic outcomes. The rapid development and application of nanomedicine have motivated this progress. Combinational regimen, for instance, has become an indispensable approach for effective cancer treatment, including the combination of chemotherapeutic agents, chemo-energy, chemo-gene, chemo-small molecules, and chemo-immunology. Additionally, smart nanoplatforms that respond to external stimuli (such as light, temperature, ultrasound, and magnetic field), and/or to internal stimuli (such as changes in pH, enzymes, hypoxia, and redox) have been extensively investigated to improve precision therapy. Smart nanoplatforms for combinational therapy have demonstrated the potential to be the next generation cancer treatment regimen. This review aims to highlight the recent advances in smart combinational therapy.

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Principles of Cancer Treatment

10.2310/im.1245 ◽

2010 ◽

Author(s):

Eric H. Rubin ◽

William N Hait

Keyword(s):

Drug Resistance ◽

Nucleic Acid ◽

Cancer Treatment ◽

Cancer Biology ◽

Performance Status ◽

Cancer Therapeutics ◽

Acid Synthesis ◽

Chemotherapeutic Agents ◽

Nucleic Acid Synthesis ◽

World Health

This review is divided into three primary sections dealing with management of cancer patients, the specific basis of cancer treatment, and specific chemotherapeutic agents. The first section outlines the diagnosis, staging, performance status, and treatment of cancer. The discussion of the specific basis of cancer treatment describes cancer biology (including its transformation and proliferation, cell viability and cell death, and invasion and metastases) and the principles of cancer pharmacology. The discussion on pharmacology details dose response and schedule, drug resistance, combination chemotherapy, common toxicities, and pharmacokinetics and pharmacogenetics. Among the specific chemotherapeutic agents discussed are drugs that alter nucleic acid synthesis or function (including DNA alkylating and cross-linking agents, inhibitors of nucleic acid synthesis, and DNA topoisomerase inhibitors); antimicrotubule drugs (eg, vinca alkaloids, taxanes, and estramustine); drugs that affect growth factors, receptors, and signal transduction pathways; drugs that inhibit metastases or angiogenesis; gene-based therapies; and immunotherapies. Tables describe the World Health Organization Performance Scale and chemotherapeutic agents, and figures illustrate targets for new cancer therapeutics and mechanisms of chemotherapeutic drug resistance. This review contains 4 highly rendered figures, 2 tables, and 90 references.

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Cytoprotective Agents to Avoid Chemotherapy Induced Sideeffects on Normal Cells: A Review

Current Cancer Drug Targets ◽

10.2174/1568009619666190326120457 ◽

2019 ◽

Vol 19 (10) ◽

pp. 765-781

Author(s):

Seema Rohilla ◽

Harish Dureja ◽

Vinay Chawla

Keyword(s):

Adverse Effects ◽

Anticancer Agents ◽

Therapeutic Index ◽

Chemotherapeutic Agents ◽

Vital Role ◽

Normal Cells ◽

Normal Tissues ◽

Organ Specific ◽

Delay In Treatment

Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.

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Prostate Cancer: Biology, Incidence, Detection Methods, Treatment Methods, and Vaccines

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200224100730 ◽

2020 ◽

Vol 20 (10) ◽

pp. 847-854

Author(s):

Ronald Bartzatt

Keyword(s):

Prostate Cancer ◽

Cancer Treatment ◽

Prostate Specific Antigen ◽

Cancer Biology ◽

Early Stage ◽

Specific Antigen ◽

Detection Methods ◽

Hormone Refractory Prostate Cancer ◽

High Risk Prostate Cancer ◽

Hormone Refractory

Cancer of the prostate are cancers in which most incidences are slow-growing, and in the U.S., a record of 1.2 million new cases of prostate cancer occurred in 2018. The rates of this type of cancer have been increasing in developing nations. The risk factors for prostate cancer include age, family history, and obesity. It is believed that the rate of prostate cancer is correlated with the Western diet. Various advances in methods of radiotherapy have contributed to lowering morbidity. Therapy for hormone- refractory prostate cancer is making progress, for almost all men with metastases will proceed to hormone-refractory prostate cancer. Smoking cigarettes along with the presence of prostate cancer has been shown to cause a higher risk of mortality in prostate cancer. The serious outcome of incontinence and erectile dysfunction result from the cancer treatment of surgery and radiation, particularly for prostate- specific antigen detected cancers that will not cause morbidity or mortality. Families of patients, as well as patients, are profoundly affected following the diagnosis of prostate cancer. Poor communication between spouses during prostate cancer increases the risk for poor adjustment to prostate cancer. The use of serum prostate-specific antigen to screen for prostate cancer has led to a greater detection, in its early stage, of this cancer. Prostate cancer is the most common malignancy in American men, accounting for more than 29% of all diagnosed cancers and about 13% of all cancer deaths. A shortened course of hormonal therapy with docetaxel following radical prostatectomy (or radiation therapy) for high-risk prostate cancer has been shown to be both safe and feasible. Patients treated with docetaxel-estramustine had a prostate-specific antigen response decline of at least 50%. Cancer vaccines are an immune-based cancer treatment that may provide the promise of a non-toxic but efficacious therapeutic alternative for cancer patients. Further studies will elucidate improved methods of detection and treatment.

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Oncogenomics and CYP450 Implications in Personalized Cancer Therapy

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692117999200517122652 ◽

2020 ◽

Vol 17 (2) ◽

pp. 104-113

Author(s):

G.K. Udayaraja ◽

I. Arnold Emerson

Keyword(s):

Cytochrome P450 ◽

Cancer Treatment ◽

Cancer Susceptibility ◽

Mutant Gene ◽

Genome Project ◽

Interdisciplinary Field ◽

Precision Therapy ◽

Personalized Cancer Therapy ◽

Personalized Cancer ◽

Genetic Events

Background: The Human Genome Project has unleashed the power of genomics in clinical practice as a choice of individualized therapy, particularly in cancer treatment. Pharmacogenomics is an interdisciplinary field of genomics that deals with drug response, based on individual genetic makeup. Objective: The main genetic events associated with carcinogenesis activate oncogenes or inactivate tumor-suppressor genes. Therefore, drugs should be specific to inactivate or regulate these mutant genes and their protein products for effective cancer treatment. In this review, we summarize how polymedication decisions in cancer treatments based on the evaluation of cytochrome P450 (CYP450) polymorphisms are applied for pharmacogenetic assessment of anticancer therapy outcomes. Results: However, multiple genetic events linked, inactivating a single mutant gene product, may be insufficient to inhibit tumor progress. Thus, genomics and pharmacogenetics directly influence a patient’s response and aid in guiding clinicians to select the safest and most effective combination of medications for a cancer patient from the initial prescription. Conclusion: This review outlines the roles of oncogenes, the importance of cytochrome P450 (CYP450) in cancer susceptibility, and its impact on drug metabolism, proposing combined approaches to achieve precision therapy.

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Carbohydrate-conjugated 4-(1,3,2-dithiarsolan-2-yl)aniline as a cytotoxic agent against colorectal cancer

RSC Advances ◽

10.1039/c8ra07860b ◽

2018 ◽

Vol 8 (71) ◽

pp. 40760-40764

Author(s):

Boqiao Fu ◽

Xiaolin Wang ◽

Yingjie Li ◽

Jingying Hu ◽

Dai Lu ◽

...

Keyword(s):

Colorectal Cancer ◽

Therapeutic Index ◽

Chemotherapeutic Agents ◽

Cytotoxic Agent ◽

Normal Cells

We synthesized a carbohydrate-conjugated 4-(1,3,2-dithiarsolan-2-yl)aniline. It exhibited reduced cytotoxicity to normal cells, suggesting a feasible approach to improve the therapeutic index of arsenic-containing compounds as chemotherapeutic agents.

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Convection Enhanced Delivery in the Setting of High-Grade Gliomas

Pharmaceutics ◽

10.3390/pharmaceutics13040561 ◽

2021 ◽

Vol 13 (4) ◽

pp. 561

Author(s):

Chibueze D. Nwagwu ◽

Amanda V. Immidisetti ◽

Michael Y. Jiang ◽

Oluwasegun Adeagbo ◽

David C. Adamson ◽

...

Keyword(s):

Rapid Development ◽

Systemic Exposure ◽

Therapeutic Index ◽

High Grade Glioma ◽

High Grade ◽

Clinical Experiences ◽

Convection Enhanced Delivery ◽

Drug Concentrations ◽

Infiltrative Growth Pattern ◽

High Grade Gliomas

Development of effective treatments for high-grade glioma (HGG) is hampered by (1) the blood–brain barrier (BBB), (2) an infiltrative growth pattern, (3) rapid development of therapeutic resistance, and, in many cases, (4) dose-limiting toxicity due to systemic exposure. Convection-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and increase therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

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In-Vitro Application of Magnetic Hybrid Niosomes: Targeted siRNA-Delivery for Enhanced Breast Cancer Therapy

Pharmaceutics ◽

10.3390/pharmaceutics13030394 ◽

2021 ◽

Vol 13 (3) ◽

pp. 394 ◽

Cited By ~ 1

Author(s):

Viktor Maurer ◽

Selin Altin ◽

Didem Ag Seleci ◽

Ajmal Zarinwall ◽

Bilal Temel ◽

...

Keyword(s):

Breast Cancer ◽

Cellular Uptake ◽

Sirna Delivery ◽

Superparamagnetic Iron Oxide ◽

Cost Effective ◽

Chemotherapeutic Agents ◽

Therapy Outcome ◽

Ionic Surfactant ◽

Combinational Therapy

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FexOy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.

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Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00448-5 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Zhenyu Ding ◽

Qing Li ◽

Rui Zhang ◽

Li Xie ◽

Yang Shu ◽

...

Keyword(s):

Lung Cancer ◽

Dendritic Cell ◽

Cancer Treatment ◽

Checkpoint Inhibitors ◽

Rapid Development ◽

Therapeutic Modality ◽

Advanced Lung Cancer ◽

Cell Vaccine ◽

Lung Cancer Treatment ◽

Dc Vaccine

AbstractNeoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3–14 doses/person). In total, 12–30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1–2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.

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Exosomes in the Tumor Microenvironment: From Biology to Clinical Applications

Cells ◽

10.3390/cells10102617 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2617

Author(s):

Vitor Rodrigues da Costa ◽

Rodrigo Pinheiro Araldi ◽

Hugo Vigerelli ◽

Fernanda D’Ámelio ◽

Thais Biude Mendes ◽

...

Keyword(s):

Tumor Microenvironment ◽

Cancer Treatment ◽

Cancer Biology ◽

Clinical Applications ◽

Future Prospects ◽

Hallmarks Of Cancer ◽

Cancer Heterogeneity ◽

Important Health ◽

Clinical Potential

Cancer is one of the most important health problems and the second leading cause of death worldwide. Despite the advances in oncology, cancer heterogeneity remains challenging to therapeutics. This is because the exosome-mediated crosstalk between cancer and non-cancer cells within the tumor microenvironment (TME) contributes to the acquisition of all hallmarks of cancer and leads to the formation of cancer stem cells (CSCs), which exhibit resistance to a range of anticancer drugs. Thus, this review aims to summarize the role of TME-derived exosomes in cancer biology and explore the clinical potential of mesenchymal stem-cell-derived exosomes as a cancer treatment, discussing future prospects of cell-free therapy for cancer treatment and challenges to be overcome.

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Genome Instability in Multiple Myeloma: Facts and Factors

Cancers ◽

10.3390/cancers13235949 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5949

Author(s):

Anna Y. Aksenova ◽

Anna S. Zhuk ◽

Artem G. Lada ◽

Irina V. Zotova ◽

Elena I. Stepchenkova ◽

...

Keyword(s):

Multiple Myeloma ◽

Complex Disease ◽

Plasma Cells ◽

Genome Instability ◽

Hematologic Malignancy ◽

Point Mutations ◽

Malignant Neoplasm ◽

Chemotherapeutic Agents ◽

Hematopoietic Stem ◽

Social Burden

Multiple myeloma (MM) is a malignant neoplasm of terminally differentiated immunoglobulin-producing B lymphocytes called plasma cells. MM is the second most common hematologic malignancy, and it poses a heavy economic and social burden because it remains incurable and confers a profound disability to patients. Despite current progress in MM treatment, the disease invariably recurs, even after the transplantation of autologous hematopoietic stem cells (ASCT). Biological processes leading to a pathological myeloma clone and the mechanisms of further evolution of the disease are far from complete understanding. Genetically, MM is a complex disease that demonstrates a high level of heterogeneity. Myeloma genomes carry numerous genetic changes, including structural genome variations and chromosomal gains and losses, and these changes occur in combinations with point mutations affecting various cellular pathways, including genome maintenance. MM genome instability in its extreme is manifested in mutation kataegis and complex genomic rearrangements: chromothripsis, templated insertions, and chromoplexy. Chemotherapeutic agents used to treat MM add another level of complexity because many of them exacerbate genome instability. Genome abnormalities are driver events and deciphering their mechanisms will help understand the causes of MM and play a pivotal role in developing new therapies.

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