Article

Modjtahedi H, Ali S, Essapen STherapeutic application of monoclonal antibodies in cancer: advances and challenges. Br Med Bull 104: 41-59

1School of Life Sciences, Kingston University London, Penrhyn Road, Kingston KT1 2EE, UK.
British Medical Bulletin (Impact Factor: 3.66). 10/2012; 104(1). DOI: 10.1093/bmb/lds032
Source: PubMed

ABSTRACT

IntroductionMonoclonal antibody (mAb)-based products are highly specific for a particular antigen. This characteristic feature of the molecules makes them an ideal tool for many applications including cancer diagnosis and therapy.Sources of dataWe performed comprehensive searches of PubMed, Medline and the Food and Drug Administration website using keywords such as 'therapeutic antibodies' and 'anti-cancer antibodies'.Areas of agreementTreatment of cancer patients with antibodies when used alone or in combination with chemotherapy and radiotherapy, or conjugated to drugs or radioisotopes, prolongs overall survival in cancer patients. Currently, there are 14 mAb-based drugs that have been approved for the treatment of cancer patients.Areas of controversyThe response of cancer patients to antibody therapy can be of short duration. Therapeutic antibodies are expensive and may have side effects. There are no reliable predictive biomarkers for sensitivity or resistance to certain therapeutic antibodies.Future focusThere should be additional studies to discover novel therapeutic targets, to develop more effective antibody-based drugs with fewer side effects, to identify more reliable predictive biomarker(s) for response to therapy with antibody-based drugs and to develop alternative strategies (e.g. transgenic plants, transgenic farm animals) for production of large quantities and more affordable batches of therapeutic antibodies.Areas timely for developing researchA better understanding of cancer biology, the hallmarks of human cancers and the immune system would lead to identification of additional cell surface biomarkers. These in turn would facilitate the development of novel and biosimilar antibody-based drugs and their routine use as 'magic bullets' for the targeted therapy of human cancers.

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    • "cancer (Wong, 2005; Wu et al, 2008; Modjtahedi et al, 2012; Arteaga and Engelman, 2014). Although the clinical efficacy of cetuximab and panitumumab has been demonstrated in many patients, the duration of response can be short, with rapid emergence of acquired resistance as a major cause of treatment failure (Cunningham et al, 2004; Douillard et al, 2010; Elez et al, 2010; Gravalos et al, 2010; Osumi et al, 2013). "
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    • "Because there are a number of specific membrane proteins in cancer cells, it might be possible to select or design new molecules that could specifically bind to these cell surface proteins to eliminate cancer cells [11]. Several studies have shown that monoclonal antibodies (mAbs) could improve tumor targeting and anticancer effects [12] [13] [14]. However, their further applications for tumor therapy are limited because of high molecular weights, low tissue penetration and poor cellular uptake [11] [15]. "
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    • "Because there are a number of specific membrane proteins in cancer cells, it might be possible to select or design new molecules that could specifically bind to these cell surface proteins to eliminate cancer cells [11]. Several studies have shown that monoclonal antibodies (mAbs) could improve tumor targeting and anticancer effects [12] [13] [14]. However, their further applications for tumor therapy are limited because of high molecular weights, low tissue penetration and poor cellular uptake [11] [15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cancer is one of the leading causes of death worldwide. Conventional cancer therapies mainly focus on mass cell killing without high specificity and often cause severe side effects and toxicities. Peptides are a novel class of anticancer agents that could specifically target cancer cells with lower toxicity to normal tissues, which will offer new opportunities for cancer prevention and treatment. Anticancer peptides face several therapeutic challenges. In this review, we present the sources and mechanisms of anticancer peptides and further discuss modification strategies to improve the anticancer effects of bioactive peptides.
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