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  1. Recent progress in small molecule agents for the targeted therapy of triple-negative breast cancer
    Islam R, Lam KW
    Eur J Med Chem, 2020 Dec 01;207:112812.
    PMID: 32937283 DOI: 10.1016/j.ejmech.2020.112812
    Triple-negative breast cancer (TNBC) is the most aggressive type of cancer, with a high risk of death on recurrence. To date, there is a lack of approved targeted agents for the treatment of the disease. Patients with TNBC continue to depend on surgery, chemotherapy, and radiotherapy, all of which have a wide side effect profile. In the present review, we highlight the current progress and exciting developments in the small-molecule targeted therapy for the treatment of TNBC. Finally, we also discuss the prospect of combining targeted therapy and immunotherapy for the effective treatment of TNBC.
    Matched MeSH terms: Small Molecule Libraries/therapeutic use
  2. Targeting Legumain As a Novel Therapeutic Strategy in Cancers
    Mai CW, Chung FF, Leong CO
    Curr Drug Targets, 2017;18(11):1259-1268.
    PMID: 27993111 DOI: 10.2174/1389450117666161216125344
    BACKGROUND: Recent reports indicate that the tumor microenvironment plays a pivotal role in cancer development and progression, leading to a paradigm shift in the way cancer is studied and targeted. In contrast to traditional approaches, where only tumor cells are targeted for the treatment, an emerging approach is to develop therapeutics which target the tumor microenvironment while complementing or enhancing current treatments. Legumain (LGMN) is a newly identified target which is highly expressed in the tumor microenvironment and in tumor cells, and holds potential both as a biomarker and as a therapeutic target.

    CONCLUSION: This review will be the first to summarize the expression of LGMN in common cancers, as well as its roles in tumorigenesis and metastasis. This review also discusses the current developments and future prospects of targeting LGMN through the development of DNA vaccines, azopeptides, small molecule inhibitors and LGMN activated prodrugs, highlighting the potential of LGMN as a target for cancer therapeutics.

    Matched MeSH terms: Small Molecule Libraries/therapeutic use
  3. Fulltext Molecular subversion of Cdc42 signalling in cancer
    Murphy NP, Binti Ahmad Mokhtar AM, Mott HR, Owen D
    Biochem Soc Trans, 2021 06 30;49(3):1425-1442.
    PMID: 34196668 DOI: 10.1042/BST20200557
    Cdc42 is a member of the Rho family of small GTPases and a master regulator of the actin cytoskeleton, controlling cell motility, polarity and cell cycle progression. This small G protein and its regulators have been the subject of many years of fruitful investigation and the advent of functional genomics and proteomics has opened up new avenues of exploration including how it functions at specific locations in the cell. This has coincided with the introduction of new structural techniques with the ability to study small GTPases in the context of the membrane. The role of Cdc42 in cancer is well established but the molecular details of its action are still being uncovered. Here we review alterations found to Cdc42 itself and to key components of the signal transduction pathways it controls in cancer. Given the challenges encountered with targeting small G proteins directly therapeutically, it is arguably the regulators of Cdc42 and the effector signalling pathways downstream of the small G protein which will be the most tractable targets for therapeutic intervention. These will require interrogation in order to fully understand the global signalling contribution of Cdc42, unlock the potential for mapping new signalling axes and ultimately produce inhibitors of Cdc42 driven signalling.
    Matched MeSH terms: Small Molecule Libraries/therapeutic use
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