A concise review on cancer treatment methods and delivery systems

doi:10.1016/j.jddst.2019.101350

Journal of Drug Delivery Science and Technology

Volume 54, December 2019, 101350

https://doi.org/10.1016/j.jddst.2019.101350 Get rights and content

Highlights

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This review discusses the wide range of recently developed cancer treatment methods.
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It highlights the latest advances in the development of delivery technologies.
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The study begins with looking at traditional strategies in cancer therapy.
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The current potential nano-carriers as novel systems is also discussed.
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The challenges involved in the promoted cancer treatments are discussed.

Abstract

The ultimate purpose of current cancer research is to develop a comprehensive treatment for cancer. Recent studies have shown an increased interest in investigating the capacity of delivery systems and pharmaceutical conjugations for cancer treatment. However, in spite of all these efforts, few attempts have been made to summarize this growing body of work. This review discusses the wide range of recently developed cancer treatment methods, highlighting the latest advances in the development of delivery technologies. This study begins with looking at traditional strategies in cancer therapy, continued by the current potential nano-carriers introducing the novel designed systems. The comprehensive deduction of various applied methods considering the clinical progress also presented. The challenges involved in those promoted cancer treatments are then discussed, to provide a clear perspective on the future of effective delivery and treatment methods.

Graphical abstract

Introduction

Following cardiovascular diseases, cancer is the second major cause of death worldwide [1,2]. Given the seriousness of the issue, it is therefore worth defining cancer. Carcinogenesis is a multistep process in which changes in tissue architecture and in cell phenotype can induce local regions of hypoxia. This promotes the survival and growth of tissue stem cells and the formation of precancerous and cancerous lesions [3]. The most fundamental trait of tumor cells is their ability to survive beyond their normal life span and to sustain chronic proliferation (the growth of normal tissue is tightly regulated). The lack of normal growth control is operative in both early tumor genesis and metastasis. In order to grow exponentially, tumor cells must circumvent pathways that negatively control cell proliferation by evading growth suppressors and resisting programmed cell death (apoptosis). Apoptotic evasion is one of the hallmarks of cancer and appears to play a key role in inducing resistance to both chemo- and radio-therapy [4].

Tumor angiogenesis, the process of growth and formation of new blood vessels (neovascularisation), is also an essential pathological feature of cancer. To be able to promote neovascularisation, tumor cells have to acquire an angiogenic phenotype. Angiogenesis is crucial for growth and spread of tumor cells, which occurs in the early stages of tumor development. Due to the higher proliferation speeds, tumor blood vessels are often described as structurally and functionally abnormal. However, they are functional enough to provide nutrients and oxygen to growing tumors and to support tumor cell dissemination and metastasis [5,6].

Metastasis is another critical aspect of tumorigenesis and the primary reason for the high mortality rate of cancer, responsible for the majority of cancer-associated death [7]. Metastasis is a complex process that requires close collaboration between cancer, immune, inflammatory, and stromal cells. It is generally divided into a number of steps including detachment of tumor cells from the primary tumor, invasion, migration, intravasation, survival in the vasculature, extravasation, and colonization of the secondary site [8,9].

Table 1 summarizes the main differences between normal and tumor cells.

Section snippets

Cancer treatment

In recent years, remarkable progress has been made towards a better understanding of cancer development, which has led to major advances in cancer treatment. However, cancer is an aggressive disease that is difficult to treat due to several reasons. These are including the major inter- and intra-tumor heterogeneity and the mutations in hundreds of different genes contributing to cancer. Further, cancer can affect a wide range of cells (e.g., epithelial, stromal, blood-based) and organs in the

Delivery strategies

Nano-conjugates with distinctive natural and structural properties have been widely investigated for tumor targeted delivery of various compounds (chemotherapeutic drugs, PS molecules, photothermal agents and genetic materials) improving their therapeutic efficiency and reducing their negative features. This category (Fig. 4) includes linear polymeric conjugates [247,248], dendrimers [[249], [250], [251], [252]], liposomes [253,254], micelles [255,256], non-polymeric nanoparticles [247,253,[257]

Novel strategies for improving the introduced nanocarriers

Advances in nanomedicine have become crucial for targeted drug delivery, early detection, and increasingly personalized approaches to cancer treatment. As mentioned in the former section, nanocarrier-based drug-delivery systems have overcome some of the limitations associated with traditional cancer-therapy, such as reduced drug solubility, chemo-resistance, systemic toxicity, and poor bioavailability. Although these systems have improved delivery of drugs into the targeting tissues, they

Tumor targeting of nano-Conjugates

Nano-conjugates, including any polymeric conjugate/system in nano dimensions, are able to deliver anticancer/therapeutic agents to the malignant tissues via three basic pathways, consisting passive, active or physical targeting (Fig. 5). Such systems overcome the limitation of conventional chemotherapeutic agents by a) Specific recognizing the tumor targeted cells b) penetrating to the cells and physiological barriers (e.g., blood-brain barrier, BBB) c) controlling the release of drug and

Ideal targeting ligands

The ideal biomarkers (to be targeted) in cancer targeted therapy needs to be abundantly and uniquely expressed on tumor cells with lower expression on non-tumor cells. Table 19 concisely describes the tumor biomarkers for various tumor types. Whether the targeted nano-carrier desires to be internalized into the directed cells is another important criterion of appropriate targeting ligands [20,530]. The targeted biomarker also needs to be easily accessible by the designed carrier.

Over-expressed

Cancer therapies and their challenges

In general, there are two important aspects must be considered in cancer therapy: targeted destruction of tumor cells with less impact on non-tumor cells, and more operative retention time in the blood circulation while RES response is limited. Proper characterization also affects the deficiency of the system designed for therapeutic aims.

Conclusion

This review concisely summarized the wide range of clinical cancer treatments, considering their benefits and potential challenges.

PDT as one of the most efficient therapies in terms of its toxicity has the potential to become a powerful approach to cancer treatment. In this method, PS molecules and PS like nanoparticles interact with the molecular oxygen producing ROS, which effectively damages the cellular constituents. However, drawbacks such as the insufficient retention time and the

Funding sources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

All authors declare that they have no conflict of interest.

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A concise review on cancer treatment methods and delivery systems

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Cancer treatment

Delivery strategies

Novel strategies for improving the introduced nanocarriers

Tumor targeting of nano-Conjugates

Ideal targeting ligands

Cancer therapies and their challenges

Conclusion

Funding sources

Declaration of competing interest

Matrix Biol.

Acta Pharm. Sin. B

Adv. Drug Deliv. Rev.

Cancer Treat Rev.

Int. J. Biochem. Cell Biol.

J. Biol. Chem.

Trends Cell Biol.

Cancer Lett.

J. Control. Release

Adv. Drug Deliv. Rev.

Cancer Cell

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Bioorg. Med. Chem.

Free Radic. Biol. Med.

J. Photochem. Photobiol. B Biol.

Dyes Pigments

Lancet Oncol.

Drug Discov. Today

Photodiagn. Photodyn. Ther.

J. Photochem. Photobiol. A Chem.

Urology

Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012

Int. J. Cancer

Cancer statistics

CA A Cancer J. Clin.

Development of cancer-initiating cells and immortalized cells with genomic instability

World J. Stem Cells

Apoptosis evasion: the role of survival pathways in prostate cancer progression and therapeutic resistance

J. Cell. Biochem.

Broad targeting of angiogenesis for cancer prevention and therapy

Cancer genome landscapes

Science

Metastasis review: from bench to bedside

Tumor Biol.

Nanoparticles for drug delivery in cancer treatment

A subset of breast cancer predisposes to brain metastasis

Med. Mol. Morphol.

Normal stem cells and cancer stem cells: similar and different

Quantitative measures to reveal coordinated cytoskeleton-nucleus reorganization during in vitro invasion of cancer cells

New J. Phys.

Normal Stem Cells and Cancer Stem Cells: Similar and Different

Cancer stem cells: models and concepts

Annu. Rev. Med.

Basal cell carcinoma: cell of origin, cancer stem cell hypothesis and stem cell markers

Br. J. Dermatol.

DNA repair, genome stability and cancer: a historical perspective

Nat. Rev. Cancer

Folate Receptor-Targeted Delivery of Small Interfering Rna to Cancer Cells

Cancer Therapies

Association of stem cell-related Markers and Survival in astrocytic gliomas

Biomarkers

A subset of breast cancer predisposes to brain metastasis

Med. Mol. Morphol.

Green tea catechins reduce invasive potential of human melanoma cells by targeting COX-2, PGE2 receptors and epithelial-to-mesenchymal transition

PLoS One

The power and the promise of liver cancer stem cell markers

Stem Cells Dev.

AC133 antigen, CD133, prominin‐1, prominin‐2, etc.: prominin family gene products in need of a rational nomenclature

Stem Cells

Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells

Oncogene

Microdomains of GPI-anchored proteins in living cells revealed by crosslinking

Nature

Cholesterol, lipid rafts, and disease