A systems approach to cancer therapy

Teicher, Beverly A.

doi:10.1007/bf00437479

Cited by 111 publications

(27 citation statements)

References 240 publications

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“…These results support the predictions of Teicher [29], who anticipates that the combination of antigiogenic drugs with conventional chemotherapy would yield optimal effects, as this combination targets two tumour compartments (cancer cells and endothelial cells). According to Teicher [29], antiangiogenic drugs should always increase the effects of cytotoxic drugs.…”

Section: Introductionsupporting

confidence: 87%

“…For example, a drug called bevacizumab, an antibody against a potent angiogenic substance secreted (among others) by cancer cells called vascular endothelial growth factor (VEGF), in combination with cytotoxic drugs yielded a significant increase in survival in colorectal cancer patients [18]. These results support the predictions of Teicher [29], who anticipates that the combination of antigiogenic drugs with conventional chemotherapy would yield optimal effects, as this combination targets two tumour compartments (cancer cells and endothelial cells). According to Teicher [29], antiangiogenic drugs should always increase the effects of cytotoxic drugs.…”

Section: Introductionmentioning

confidence: 59%

“…Although Teicher [29] appears to have reached the right conclusion, her "linear" reasoning, which is typical of attempts by biologists to establish a non-quantitative theoretical framework [9], neglects many of the complex interactions between the different elements involved in the process of tumour growth. Our aim in this paper is to place Teicher's theoretical ideas in a quantitative framework which allows us first to check their validity and then to explore possible mechanisms involved in the improvement of the efficacy of cytotoxic drugs administered together with antiangiogenic drugs.…”

Section: Introductionmentioning

confidence: 96%

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Multiscale Modelling of Tumour Growth and Therapy: The Influence of Vessel Normalisation on Chemotherapy

Alarcón

Owen

Byrne

et al. 2006

Computational and Mathematical Methods in Medicine

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Following the poor clinical results of antiangiogenic drugs, particularly when applied in isolation, tumour biologists and clinicians are now turning to combinations of therapies in order to obtain better results. One of these involves vessel normalisation strategies. In this paper, we investigate the effects on tumour growth of combinations of antiangiogenic and standard cytotoxic drugs, taking into account vessel normalisation. An existing multiscale framework is extended to include new elements such as tumour-induced vessel dematuration. Detailed simulations of our multiscale framework allow us to suggest one possible mechanism for the observed vessel normalisation-induced improvement in the efficacy of cytotoxic drugs: vessel dematuration produces extensive regions occupied by quiescent (oxygen-starved) cells which the cytotoxic drug fails to kill. Vessel normalisation reduces the size of these regions, thereby allowing the chemotherapeutic agent to act on a greater number of cells.

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Section: Introductionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 96%

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Multiscale Modelling of Tumour Growth and Therapy: The Influence of Vessel Normalisation on Chemotherapy

Alarcón

Owen

Byrne

et al. 2006

Computational and Mathematical Methods in Medicine

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“…Therefore, rmES treatment induces cell death rather than inhibiting cell proliferation, suggesting that ES treatment is more suitable as adjuvant therapy or in combination with RT. Results of this study confirm those of previous studies and demonstrate that rmES potentiates the cytotoxic effects of RT (5,6,(27)(28)(29)(30). Of note, however, is that the results do not indicate the benefits of combination therapy.…”

Section: Discussionsupporting

confidence: 90%

Endostatin enhances radioresponse in breast cancer cells via alteration of substance P levels

Aydemir

Korcum

et al. 2011

Oncol Lett

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Abstract. Radiotherapy is widely used in the treatment of cancer. On the other hand, endostatin is considered to be a potent inhibitor of angiogenesis. Therefore, to test whether ES combined with RT overcomes the limitations of each monotherapy the present study investigated the effects of endostatin (ES), radiotherapy (RT) or combination therapy on the growth of mouse breast cancer cells as well as on the expression of substance P in vitro. The breast cancer cell lines 4T1 and 4THMpc were treated with recombinant murine ES (0.5, 1, 2, 4 and 8 µg/ml) alone, RT (45 Gy) alone or as a combination therapy. Cell proliferation was evaluated using an MTS assay and the results were verified by the Live/Dead assay. Immunoprecipitation and Western blotting analysis were performed to determine whether the substance P levels of the two cell lines occurred due to substance P content. Results showed that ES alone resulted in a low but significant inhibition in the growth of 4T1 and 4THMpc cell lines (27.63 and 21.75%, respectively). RT alone inhibited the growth of 4T1 (30.81%) and 4THMpc (39.64%) cells. A combination of ES with RT enhanced growth inhibition in the cells (83% in 4T1 and 80% in 4THMpc). The amount of substance P, both in the conditioned media and the cell lysates, increased within 72 h after RT. This increase was inhibited when ES and RT were applied in combination. These data indicate that ES inhibits the in vitro growth of breast cancer cells and potentiates the antitumor effects of RT at appropriate doses via alteration of the amount of substance P and thus an increase of radioresponse.

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“…Tumors are dynamic, complex, living tissues undergoing varied processes of tissue growth under the guidance of aberrant malignant cells. The active involvement of normal cells in the vicinity of a malignant colony is required for a tumor mass to grow, and these normal cells become a major component of the malignant disease 21. The corollary is that both the normal and the cancer cells that comprise malignant disease are valid targets for therapeutic intervention.…”

Section: Angiogenic Targetsmentioning

confidence: 99%

Characteristics of human Ewing/PNET sarcoma models

Teicher¹,

Rouleau²,

Kruger³

et al. 2011

Annals of Saudi Medicine

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Ewing/PNET (peripheral neuroepithelioma) tumors are rare aggressive bone sarcomas occurring in young people. Rare-disease clinical trials can require global collaborations and many years. In vivo models that as accurately as possible reflect the clinical disease are helpful in selecting therapeutics with the most promise of positive clinical impact. Human Ewing/PNET sarcoma cell lines developed over the past 45 years are described. Several of these have undergone genetic analysis and have been confirmed to be those of Ewing/PNET sarcoma. The A673 Ewing sarcoma line has proven to be particularly useful in understanding the biology of this disease in the mouse. The chromosomal translocation producing the EWS/FLI1 fusion transcript characterizes clinical Ewing sarcoma. Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma. The A673 Ewing sarcoma line grows in culture and as a xenograft in immunodeficient mice. The A673 model has been used to study Ewing sarcoma angiogenesis and response to antiangiogenic agents. Many Ewing sarcoma clinical specimens express the cell surface protein endosialin. Several Ewing sarcoma cell lines, including the A673 line, also express cell surface endosialin when grown as subcutaneous tumor nodules and as disseminated disease; thus the A673 is a useful model for the study of endosialin biology and endosialin-directed therapies. With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets. Ewing PNET sarcomas are a rare disease where models are available.

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A systems approach to cancer therapy

Cited by 111 publications

References 240 publications

Multiscale Modelling of Tumour Growth and Therapy: The Influence of Vessel Normalisation on Chemotherapy

Multiscale Modelling of Tumour Growth and Therapy: The Influence of Vessel Normalisation on Chemotherapy

Endostatin enhances radioresponse in breast cancer cells via alteration of substance P levels

Characteristics of human Ewing/PNET sarcoma models

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