Breathing New Life into Old Drugs: Indication Discovery by Systems Directed Therapy

Bundscherer, Annika; Hafner, Christian

doi:10.1007/978-90-481-9531-2_24

Cited by 5 publications

(5 citation statements)

References 126 publications

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“…Many targeted therapies , also those used in the current trials, may be repurposed, as their activity profile is strongly dependent on the tumor type and stroma composition, and - as shown by cellular therapies in situ - on the co-regulatory activity profile of the combination partners [ 9 , 51 ]. In anakoinotic therapy schedules, the sum of single known drug activities may establish a completely novel quality of action in the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…Cellular therapies in situ, presented here, consisted of two major components, dual transcriptional modulation [ 11 – 13 ] combined with drugs, which may enhance the activity profile of transcriptional modulators, i.e., metronomic low-dose chemotherapy (angiostatic, immune modulatory) [ 14 ] or low-dose 5-azacytidine (epigenetic reprogramming). A third component was added in some trials, namely classic targeted therapies (imatinib, COX-2 inhibitors, lenalidomide and mTor-inhibitors), again in a drug repurposing manner to intensify the angiostatic, anti-inflammatory, and immune modulatory activity profile (Table 1 ) [ 9 , 10 ].…”

Section: Methodsmentioning

confidence: 99%

“…Primary aim of cellular therapies in situ is the communicative reprogramming of tumor systems (anakoinosis) for diversifying palliative care, moreover, for uncovering novel ways for the induction of tumor cell death. Cellular therapies in situ comprise repurposed drugs [ 9 , 10 ] with poor monoactivity, but concerted regulatory activity, such as transcriptional modulators (dual transcriptional modulation) [ 11 – 13 ], metronomic low-dose chemotherapy [ 14 ], and classic targeted therapies [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Anakoinosis: Communicative Reprogramming of Tumor Systems - for Rescuing from Chemorefractory Neoplasia

Hart

Vogelhuber

Wolff

et al. 2015

Cancer Microenvironment

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Disruptive technologies, such as communicative reprogramming (anakoinosis) with cellular therapies in situ for treating refractory metastatic cancer allow patient care to accelerate along a totally new trajectory and highlight what may well become the next sea change in the care of patients with many types of advanced neoplasia. Cellular therapy in situ consisted of repurposed drugs, pioglitazone plus all-trans retinoic acid or dexamethasone or interferon-alpha (dual transcriptional modulation) combined with metronomic low-dose chemotherapy or low-dose 5-azacytidine, plus/minus classic targeted therapy. The novel therapeutic tools for specifically designing communication processes within tumor diseases focus on redirecting (1) rationalizations of cancer hallmarks (constitution of single cancer hallmarks), (2) modular events, (3) the ‘metabolism’ of evolutionary processes (the sum of therapeutically and intrinsically inducible evolutionary processes) and (4) the holistic communicative context, which determines validity and denotation of tumor promoting communication lines. Published data on cellular therapies in situ (6 histologic tumor types, 144 patients, age 0.9–83 years) in castration-resistant prostate cancer, pretreated renal clear cell carcinoma, chemorefractory acute myelocytic leukemia, multiple myeloma > second-line, chemorefractory Hodgkin lymphoma or multivisceral Langerhans cell histiocytosis, outline the possibility for treating refractory metastatic cancer with the hope that this type of reprogrammed communication will be scalable with minimal toxicity. Accessibility to anakoinosis is a tumor inherent feature, and cellular therapy in situ addresses extrinsic and intrinsic drug resistance, by redirecting convergent organized communication tools, while been supported by quite different pattern of (molecular-)genetic aberrations.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Anakoinosis: Communicative Reprogramming of Tumor Systems - for Rescuing from Chemorefractory Neoplasia

Hart

Vogelhuber

Wolff

et al. 2015

Cancer Microenvironment

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“…In addition, several molecules related to drug repurposing are available in Table 2 by US National Institutes of Health (NIH) on April 21 2011 with pharmaceutical industry leadership. These drugs have been proven safe in clinical trials [55][56][57][58]. For example, raltegravir (12) is HIV-1 integrase inhibitor approved by the FDA in 2006, Rob Hromas, MD (UNMCC) and clinical scientists at UNM identified it as a potential drug for adjuvant therapy in cancer [59,60].…”

Section: Drug Repurposingmentioning

confidence: 99%

Polypharmacology in Drug Discovery: A Review from Systems Pharmacology Perspective

Zhang¹,

Bai²,

Wang

et al. 2016

CPD

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“…These projects are summarized in Table 1. Several reviews [19,20] and techniques [21,22,23] related to drug repurposing are available.…”

Section: Drug Repurposing At Unmmentioning

confidence: 99%

Drug repurposing from an academic perspective

Oprea

Bauman

Bologa

et al. 2011

Drug Discovery Today: Therapeutic Strategies

276

177

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Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for a number of drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate, astemizole, R-naproxen, ketorolac, tolfenamic acid, phenothiazines, methylergonovine maleate and beta-adrenergic receptor drugs, respectively. Based on this multi-year, multi-project experience we discuss strengths and weaknesses of academic-based drug repurposing research. Translational, target and disease foci are strategic advantages fostered by close proximity and frequent interactions between basic and clinical scientists, which often result in discovering new modes of action for approved drugs. On the other hand, lack of integration with pharmaceutical sciences and toxicology, lack of appropriate intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process world-wide, and the development of pre-competitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific information for drugs world-wide, are among the ideas proposed to improve the process of academic drug discovery and repurposing, and to overcome the “valley of death” by bridging basic to clinical sciences.

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Breathing New Life into Old Drugs: Indication Discovery by Systems Directed Therapy

Cited by 5 publications

References 126 publications

Anakoinosis: Communicative Reprogramming of Tumor Systems - for Rescuing from Chemorefractory Neoplasia

Anakoinosis: Communicative Reprogramming of Tumor Systems - for Rescuing from Chemorefractory Neoplasia

Polypharmacology in Drug Discovery: A Review from Systems Pharmacology Perspective

Drug repurposing from an academic perspective

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