Tissue-selective therapy of cancer

Mv, Blagosklonny

doi:10.1038/sj.bjc.6601256

Cited by 82 publications

(68 citation statements)

References 38 publications

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“…Previously developed concepts and strategies of highly selective tumor targeting [26][27][28][29][30][31][32][33][34][35][36][37] can take advantage of spatial-temporal cell cycle imaging of a tumor described in the present report.…”

Section: Discussionmentioning

confidence: 99%

“…A subpopulation of a tissue can be targeted to reduce toxicity even further. 27,28 De-differentiation of a tumor leading to therapy resistance is a limitation of tissue-selective therapy, since the targeted protein or pathway may no longer be expressed in the de-differentiated tumor. Therefore, tissue-selective therapy can be combined with differentiation therapy as well as anti-angiogenic and standard therapy for more effective outcomes or by novel approaches such as targeting of PSA, a prostate-specific protease, by prodrugs specifically cleaved by the protease in androgen-resistant prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

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Spatial–temporal FUCCI imaging of each cell in a tumor demonstrates locational dependence of cell cycle dynamics and chemoresponsiveness

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Spatial–temporal FUCCI imaging of each cell in a tumor demonstrates locational dependence of cell cycle dynamics and chemoresponsiveness

et al. 2014

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“…Logically, the goal of anticancer therapy is to exploit the differences between normal and cancer cells. Instead of discriminating cancer and normal cells, it may be easier to exploit peculiarities of normal tissues: incorporation of iodine by thyroid or dependence on androgens, estrogens and thyroid-stimulating hormone (TSH) for prostate, breast, and thyroid tissues, respectively (Blagosklonny, 2003c). As another example, glucocorticoids inhibit proliferation and induce apoptosis in normal lymphocytes and, therefore, are effective against malignant lymphoid cells.…”

Section: Tissue-selective Therapymentioning

confidence: 99%

“…immunosuppression). Targeting a subtissue instead of an entire tissue will decrease side effects (Blagosklonny, 2003c).…”

Section: Tissue-selective Therapymentioning

confidence: 99%

“…As another example, tissue-selective therapies of prostate and thyroid cancers with antiandrogens and radioactive iodine, respectively, are very selective and effective, causing clinical responses and remissions. These effective therapies eventually select for drug resistance, associated with tumor progression (Blagosklonny, 2003c). Development of resistance, which is accompanied by dedifferentiation, is an inherent limitation of tissue-selective therapy.…”

Section: Selection For Drug Resistance: Hallmark Of Effective Therapymentioning

confidence: 99%

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Prospective strategies to enforce selectively cell death in cancer cells

Blagosklonny

2004

Oncogene

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Although induction of apoptosis (cell death mediated by caspases) determines response to cancer therapy, this approach is limited by lack of selectivity in available apoptosis-inducing agents. Furthermore, most cancers, almost by definition, are resistant to apoptosis, growth arrest and cell senescence. Then, how can anticancer agents kill cancer cell without unacceptable toxicity to a patient? The potential therapeutic approaches range from selective inhibition of antiapoptotic pathways, antiangiogenic therapy, tissue-selective therapy (including immunotherapy) to exploitation of, for example, drug resistance, oncoprotein addiction, unrestricted cell cycles, hypermitogenic and hypoxic features of cancer cells. These overlapping and complementary approaches rely on rational drug combinations (at mechanism-based doses and sequences) aimed at matching targets. To ensure killing of cancer cells selectively, we may combine apoptosis-and senescence-inducing agents with inhibitors of apoptosis (to protect normal cells), inhibitors of signal transduction with cell cycle-dependent chemotherapy, antiangiogenic agents with hypoxia-inducible factor-1 inhibitors, tissue-selective therapy with differentiating agents and activators of death receptors with chemotherapy. In theory, consecutive use of these drug combinations may control cancer.

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Recombinant nanobody against MUC1 tandem repeats inhibits growth, invasion, metastasis, and vascularization of spontaneous mouse mammary tumors

et al. 2021

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Alteration in glycosylation pattern of MUC1 mucin tandem repeats during carcinomas has been shown to negatively affect adhesive properties of malignant cells and enhance tumor invasiveness and metastasis. In addition, MUC1 overexpression is closely interrelated with angiogenesis, making it a great target for immunotherapy. Alongside, easier interaction of nanobodies (single‐domain antibodies) with their antigens, compared to conventional antibodies, is usually associated with superior desirable results. Herein, we evaluated the preclinical efficacy of a recombinant nanobody against MUC1 tandem repeats in suppressing tumor growth, angiogenesis, invasion, and metastasis. Expressed nanobody demonstrated specificity only toward MUC1‐overexpressing cancer cells and could internalize in cancer cell lines. The IC50 values (the concentration at which the nanobody exerted half of its maximal inhibitory effect) of the anti‐MUC1 nanobody against MUC1‐positive human cancer cell lines ranged from 1.2 to 14.3 nm. Similar concentrations could also effectively induce apoptosis in MUC1‐positive cancer cells but not in normal cells or MUC1‐negative human cancer cells. Immunohistochemical staining of spontaneously developed mouse breast tumors prior to in vivo studies confirmed cross‐reactivity of nanobody with mouse MUC1 despite large structural dissimilarities between mouse and human MUC1 tandem repeats. In vivo, a dose of 3 µg nanobody per gram of body weight in tumor‐bearing mice could attenuate tumor progression and suppress excessive circulating levels of IL‐1a, IL‐2, IL‐10, IL‐12, and IL‐17A pro‐inflammatory cytokines. Also, a significant decline in expression of Ki‐67, MMP9, and VEGFR2 biomarkers, as well as vasculogenesis, was evident in immunohistochemically stained tumor sections of anti‐MUC1 nanobody‐treated mice. In conclusion, the anti‐MUC1 tandem repeat nanobody of the present study could effectively overcome tumor growth, invasion, and metastasis.

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Tissue-selective therapy of cancer

Cited by 82 publications

References 38 publications

Spatial–temporal FUCCI imaging of each cell in a tumor demonstrates locational dependence of cell cycle dynamics and chemoresponsiveness

Spatial–temporal FUCCI imaging of each cell in a tumor demonstrates locational dependence of cell cycle dynamics and chemoresponsiveness

Prospective strategies to enforce selectively cell death in cancer cells

Recombinant nanobody against MUC1 tandem repeats inhibits growth, invasion, metastasis, and vascularization of spontaneous mouse mammary tumors

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