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Therapeutic options for the 2019 novel coronavirus (2019-nCoV)

期刊: NATURE REVIEWS DRUG DISCOVERY, 2020; 19 (3)

Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials.

Therapeutic strategies for hepatitis B virus infection: towards a cure

期刊: NATURE REVIEWS DRUG DISCOVERY, 2019; 18 (11)

Chronic hepatitis B virus (HBV) infection is a common cause of liver disease globally, with a disproportionately high burden in South-East Asia. Vaccines and nucleoside or nucleotide drugs are available and reduce both new infection rates and the development of liver disease in HBV-positive persons who adhere to long-term suppressive treatment. Although there is still considerable value in optimizing access to virus-suppressing regimens, the scientific and medical communities have embarked on a concerted journey to identify new antiviral drugs and immune interventions aimed at curing infection. The mechanisms and drug targets being explored are diverse; however, the field universally recognizes the importance of addressing the persistence of episomal covalently closed circular DNA, the existence of integrated HBV DNA in the host genome and the large antigen load, particularly of hepatitis B surface antigen. Another major challenge is to reinvigorate the exhausted immune response within the liver microenvironment. Ultimately, combinations of new drugs will be required to cure infection. Here we critically review the recent literature that describes the rationale for curative therapies and the resulting compounds that are being tested in clinical trials for hepatitis B.

JIF:57.62

Turning foes to friends: targeting cancer-associated fibroblasts

期刊: NATURE REVIEWS DRUG DISCOVERY, 2019; 18 (2)

Current paradigms of cancer-centric therapeutics are usually not sufficient to eradicate the malignancy, as the cancer stroma may prompt tumour relapse and therapeutic resistance. Among all the stromal cells that populate the tumour microenvironment, cancer-associated fibroblasts (CAFs) are the most abundant and are critically involved in cancer progression. CAFs regulate the biology of tumour cells and other stromal cells via cell-cell contact, releasing numerous regulatory factors and synthesizing and remodelling the extracellular matrix, and thus these cells affect cancer initiation and development. The recent characterization of CAFs based on specific cell surface markers not only deepens our insight into their phenotypic heterogeneity and functional diversity but also brings CAF-targeting therapies for cancer treatment onto the agenda. In this Review, we discuss the current knowledge of biological hallmarks, cellular origins, phenotypical plasticity and functional heterogeneity of CAFs and underscore their contribution to cancer progression. Moreover, we highlight relevant translational advances and potential therapeutic strategies that target CAFs for cancer treatment.

JIF:57.62

Lessons from immuno-oncology: a new era for cancer nanomedicine?

期刊: NATURE REVIEWS DRUG DISCOVERY, 2017; 16 (6)

Despite a decade of intensive preclinical research, the translation of cancer nanomedicine to the clinic has been slow. Here, we discuss how recent lessons learned from the successes with immuno-oncology therapies could be applied to cancer nanomedicine and how this may help to overcome some of the key technical challenges in this field.

JIF:50.17

Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targets

期刊: NATURE REVIEWS DRUG DISCOVERY, 2017; 16 (1)

Mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), exist in many tissues and are known to actively migrate to sites of tissue injury, where they participate in wound repair. Tumours can be considered "wounds that never heal" and, in response to cues from a tumour, MSCs are continuously recruited to and become integral components of the tumour microenvironment. Recently, it has become apparent that such tumour-associated MSCs (TA-MSCs) have an active role in tumour initiation, promotion, progression and metastasis. In this Review, we discuss recent advances in our understanding of the pathogenic role of TA-MSCs in regulating the survival, proliferation, migration and drug resistance of tumour cells, as well as the influence of MSCs on the immune status of the tumour microenvironment. Moreover, we discuss therapeutic approaches that target TA-MSC upstream or downstream modulators or use MSCs as vehicles for the delivery of tumoricidal agents. It is anticipated that new insights into the functions of TA-MSCs will lead to the development of novel therapeutic strategies against tumours.

JIF:50.17

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