Immunotherapies are the most rapidly growing drug class and have a major impact in oncology and on human health. It is increasingly clear that the effectiveness of immunomodulatory strategies depends on the presence of a baseline immune response and on unleashing of pre-existing immunity. Therefore, a general consensus emerged on the central part played by effector T cells in the antitumour responses. Recent technological, analytical and mechanistic advances in immunology have enabled the identification of patients who are more likely to respond to immunotherapy. In this Review, we focus on defining hot, altered and cold tumours, the complexity of the tumour microenvironment, the Immunoscore and immune contexture of tumours, and we describe approaches to treat such tumours with combination immunotherapies, including checkpoint inhibitors. In the upcoming era of combination immunotherapy, it is becoming critical to understand the mechanisms responsible for hot, altered or cold immune tumours in order to boost a weak antitumour immunity. The impact of combination therapy on the immune response to convert an immune cold into a hot tumour will be discussed.

Approaches to treat immune hot, altered and cold tumours with combination immunotherapies

Nucleic acid aptamers, often termed 'chemical antibodies', are functionally comparable to traditional antibodies, but offer several advantages, including their relatively small physical size, flexible structure, quick chemical production, versatile chemical modification, high stability and lack of immunogenicity. In addition, many aptamers are internalized upon binding to cellular receptors, making them useful targeted delivery agents for small interfering RNAs (siRNAs), microRNAs and conventional drugs. However, several crucial factors have delayed the clinical translation of therapeutic aptamers, such as their inherent physicochemical characteristics and lack of safety data. This Review discusses these challenges, highlighting recent clinical developments and technological advances that have revived the impetus for this promising class of therapeutics.

Aptamers as targeted therapeutics: current potential and challenges

해외산업간호정보 - 미국 산업안전보건연구원(National Institute for Occupational Safety and Health) 소개

The RNA interference (RNAi) pathway regulates mRNA stability and translation in nearly all human cells. Small double-stranded RNA molecules can efficiently trigger RNAi silencing of specific genes, but their therapeutic use has faced numerous challenges involving safety and potency. However, August 2018 marked a new era for the field, with the US Food and Drug Administration approving patisiran, the first RNAi-based drug. In this Review, we discuss key advances in the design and development of RNAi drugs leading up to this landmark achievement, the state of the current clinical pipeline and prospects for future advances, including novel RNAi pathway agents utilizing mechanisms beyond post-translational RNAi silencing.

The current state and future directions of RNAi-based therapeutics.

Smart nanocarrier-based drug delivery systems for cancer therapy and toxicity studies: A review

A number of anti-angiogenesis drugs have been FDA-approved and are being used in cancer treatment, and a number of other agents are in different stages of clinical development or in preclinical evaluation. However, pharmacologic anti-angiogenesis strategies that arrest tumor progression might not be enough to eradicate tumors. Decreased anti-angiogenesis activity in single mechanism-based anti-angiogenic strategies is due to the redundancy, multiplicity, and development of compensatory mechanism by which blood vessels are remodeled. Improving anti-angiogenesis drug efficacy will require identification of broad-spectrum anti-angiogenesis targets. These strategies may have novel features, such as increased porosity, and are the result of complex interactions among endothelial cells, extracellular matrix proteins, growth factors, pericyte, and smooth muscle cells. Thus, combinations of anti-angiogenic drugs and other anticancer strategies such as chemotherapy appear essential for optimal outcome in cancer patients. This review will focus on the role of anti-angiogenesis strategies in cancer treatment.

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The Role of Angiogenesis in Cancer Treatment.

https://europepmc.org/articles/PMC3955949?pdf=render

Stable RNA nanoparticles as potential new generation drugs for cancer therapy

The field of nanotechnology has led to the development of many innovative strategies for effective detection and treatment of cancer, overcoming limitations associated with conventional cancer diagnosis and therapy. Multifunctional nanoparticle systems can integrate imaging, targeting and treatment moieties on the surface and in the core, resulting in targeted delivery of the imaging or treatment modalities, specifically to the tumor. Multifunctional nanoparticles also enable simultaneous delivery of multiple treatment agents, resulting in effective combinatorial therapeutic regimens against cancer. In this review, various multifunctional nanoparticle systems that feature a variety of targeting moieties for in vitro and/or in vivo cancer imaging and therapy are discussed.

Multifunctional Nanomaterials and Their Applications in Drug Delivery and Cancer Therapy.

Flavonoids have recently attracted a great interest as potential therapeutic drugs against a wide range of free-radical-mediated diseases. The anticancer and antiviral activities of these natural products are implicated in their mechanism of actions. While the antioxidant activity of these natural polyphenolic compounds is well known, their bindings to DNA are not fully investigated. This study was designed to examine the interactions of morin (Mor), naringin (Nar), and apigenin (Api) with calf thymus DNA in aqueous solution at physiological conditions, using constant DNA concentration (6.25 mM) and various drug/DNA(phosphate) ratios of 1/40 to 1. FTIR and UV–Vis spectroscopic methods were used to determine the ligand binding modes, the binding constant, and the stability of DNA in flavonoid–DNA complexes in aqueous solution. Spectroscopic evidence shows both intercalation and external binding of flavonoids to DNA duplex with overall binding constants of Kmorin = 5.99 × 103 M−1, Kapigenin = 7.10 × 104 M−1...

DNA adducts with antioxidant flavonoids: morin, apigenin, and naringin.

A series of furo[3,2-c]coumarin derivatives 1a–d were synthesized and evaluated for their antiproliferative activity against MCF-7 breast and HCT-15 colon cancer cell lines using Sulfo-rhodamine B (SRB) assay. Compounds 1b and 1d showed higher antiproliferative activity than 1a and 1c . UV–Vis spectroscopy was used for DNA and BSA-binding affinity of the compounds 1b and 1d and gave overall affinity constants of K 1b -DNA  = 8.1 × 10 3  M −1 , K 1d -DNA  = 1.1 × 10 4  M −1 , K 1b -BSA  = 5.1 × 10 4  M −1 , and K 1d -BSA  = 7.6 × 10 4  M −1 . Our findings could provide new evidence showing the relationship between the chemical structure and anticancer activity of these new coumarin analogs.

Mehdi Rajabi

Papers

The Role of Angiogenesis in Cancer Treatment.

Stable RNA nanoparticles as potential new generation drugs for cancer therapy

Multifunctional Nanomaterials and Their Applications in Drug Delivery and Cancer Therapy.

DNA adducts with antioxidant flavonoids: morin, apigenin, and naringin.

Synthesis of a new class of furo[3,2-c]coumarins and its anticancer activity.