Skip to main content
Top
Published in: Cancer Microenvironment 1/2009

Open Access 01-09-2009

Principles of Modular Tumor Therapy

Authors: Albrecht Reichle, Gerhard C. Hildebrandt

Published in: Cancer Microenvironment | Special Issue 1/2009

Login to get access

Abstract

Nature is interwoven with communication and is represented and reproduced through communication acts. The central question is how may multimodal modularly acting and less toxic therapy approaches, defined as modular therapies, induce an objective response or even a continuous complete remission, although single stimulatory or inhibitingly acting drugs neither exert mono-activity in the respective metastatic tumor type nor are they directed to potentially ‘tumor-specific’ targets. Modularity in the present context is a formal pragmatic communicative systems concept, describing the degree to which systems objects (cells, pathways etc.) may be communicatively separated in a virtual continuum, and recombined and rededicated to alter validity and denotation of communication processes in the tumor. Intentional knowledge, discharging in reductionist therapies, disregards the risk-absorbing background knowledge of the tumor’s living world including the holistic communication processes, which we rely on in every therapy. At first, this knowledge constitutes the validity of informative intercellular processes, which is the prerequisite for therapeutic success. All communication-relevant steps, such as intentions, understandings, and the appreciation of messages, may be modulated simultaneously, even with a high grade of specificity. Thus, modular therapy approaches including risk-absorbing and validity-modifying background knowledge may overcome reductionist idealizations. Modular therapies show modular events assembled by the tumor’s living world as an additional evolution-constituting dimension. This way, modular knowledge may be acquired from the environment, either incidentally or constitutionally. The new communicatively defined modular coherency of environment, i.e. the tumor-associated microenvironment, and tumor cells open novel ways for the scientific community in ‘translational medicine’.
Glossary
Co-option
Reuse of existing genetic components, metabolic reactions, or signaling modules in diverse biological systems, such as tumors, for instance, discharging in the evolution of patterns of dysregulated transcription factors.
Evolvability
The capacity of an organism or a biological system to generate new heritable phenotypes. Therapeutical modularly induced evolutionary steps advance this definition: Modularity may allow retrospectively established spaces for primarily none-heritable evolutionary developments, if modular events (therapy) are implemented.
Modularity
In the present context, modularity is a formal pragmatic communicative systems concept, describing the degree and specificity to which systems objects (cells, pathways, etc.) may be communicatively separated in a virtual continuum and recombined and rededicated to alter the validity and denotation of communication processes in the tumor.
Modular communication (therapies)
The function is to configure the coherence between the validity and denotation of communication processes. Modular therapies may supplement prepositional aspects of communication, i.e. the presence of the tumor’s living world by normative aspects, namely by therapy-derived yes or no statements (‘know that’).
Risk-absorbing background knowledge
This knowledge constitutes the validity of informative intercellular processes, which is the prerequisite for therapeutic success. Background knowledge about the tumor’s living world is subjected to other conditions of scientific comprehension: Intentional ways fail to describe risk-absorbing knowledge, in which context-dependent knowledge about commonly administered reductionist therapy approaches is rooted. After this second objectifying step (physicians as operators of tumor systems), the network of the holistic communicative activities turns out to be the medium through which the tumor’s living world is mirrored and generated.
Tumor’s living world
The living world comprises the tumor’s holistic communication processes, which we rely on in every therapy. The living world of morphologically defined tumor cell systems creates the term opposite to those idealizations, which originally constitute scientific (intentional) knowledge. The living world is uncovered by redeeming the validity of communicative tumor processes by implementing the modular knowledge of cellular and external environments (for instance for therapeutic requirements). Only with experimental or therapeutic experiences (modular therapies) is the tumor’s living world separated into categories of knowledge, for example, into modular systems. Specific conditions of compliance for redeeming validity constitute relations between communication technique (specified modular therapy approaches) and distinct tumor-associated situation-engraved systems stages.
Reconstruction of tumor-associated systems
Redeeming validity is tailored on the relation of modular communication to the objective features of the tumor compartment, the reconstructible evolutionary (modular) systems.
Robustness
The inherent property of a system to maintain normal performance despite external and internal perturbations.
Separated or separating ‘social’ tumor systems
The possibility for redeeming novel validity by modular therapies is indicative for the existence of biologically separated or separating ‘social’ systems, i.e. in our context, metastatic tumors: Tumors constitute a solitary world with an internal context.
Literature
2.
go back to reference Hochhaus A (2008) First-Line management of CML: a state of the art review. J Natl Compr Canc Netw 6(Suppl 2):S1–S10PubMed Hochhaus A (2008) First-Line management of CML: a state of the art review. J Natl Compr Canc Netw 6(Suppl 2):S1–S10PubMed
3.
go back to reference Sonnenschein C, Soto AM (2008) Theories of carcinogenesis: an emerging perspective. Semin Cancer Biol 18:372–377PubMedCrossRef Sonnenschein C, Soto AM (2008) Theories of carcinogenesis: an emerging perspective. Semin Cancer Biol 18:372–377PubMedCrossRef
4.
go back to reference Trosko JE (2007) Gap junctional intercellular communication as a biological “Rosetta stone” in understanding, in a systems biological manner, stem cell behavior, mechanisms of epigenetic toxicology, chemoprevention and chemotherapy. J Membr Biol 218:93–100PubMedCrossRef Trosko JE (2007) Gap junctional intercellular communication as a biological “Rosetta stone” in understanding, in a systems biological manner, stem cell behavior, mechanisms of epigenetic toxicology, chemoprevention and chemotherapy. J Membr Biol 218:93–100PubMedCrossRef
5.
go back to reference Aebersold R, Auffray C, Baney E, Barillot E, Brazma A, Brett C, Brunak S, Butte A, Califano A, Celis J, Cufer T, Ferrell J, Galas D, Gallahan D, Gatenby R, Goldbeter A, Hace N, Henney A, Hood L, Iyengar R, Jackson V, Kallioniemi O, Klingmuller U, Kolar P, Kolch W, Kyriakopoulou C, Laplace F, Lehrach H, Marcus F, Matrisian L, Nolan G, Pelkmans L, Potti A, Sander C, Seljak M, Singer D, Sorger P, Stunnenberg H, Superti-Furga G, Uhlen M, Vidal M, Weinstein J, Wigle D, Williams M, Wolkenhauer O, Zhivotovsky B, Zinovyev A, Zupan B (2009) Report on EU-USA workshop: how systems biology can advance cancer research (27 October 2008). Mol Oncol 3:9–17PubMedCrossRef Aebersold R, Auffray C, Baney E, Barillot E, Brazma A, Brett C, Brunak S, Butte A, Califano A, Celis J, Cufer T, Ferrell J, Galas D, Gallahan D, Gatenby R, Goldbeter A, Hace N, Henney A, Hood L, Iyengar R, Jackson V, Kallioniemi O, Klingmuller U, Kolar P, Kolch W, Kyriakopoulou C, Laplace F, Lehrach H, Marcus F, Matrisian L, Nolan G, Pelkmans L, Potti A, Sander C, Seljak M, Singer D, Sorger P, Stunnenberg H, Superti-Furga G, Uhlen M, Vidal M, Weinstein J, Wigle D, Williams M, Wolkenhauer O, Zhivotovsky B, Zinovyev A, Zupan B (2009) Report on EU-USA workshop: how systems biology can advance cancer research (27 October 2008). Mol Oncol 3:9–17PubMedCrossRef
6.
go back to reference Reichle A, Vogt T (2008) Systems biology: a therapeutic target for tumor therapy. Cancer Microenviron 1:159–170PubMedCrossRef Reichle A, Vogt T (2008) Systems biology: a therapeutic target for tumor therapy. Cancer Microenviron 1:159–170PubMedCrossRef
8.
go back to reference Witz IP (2008) Tumor-microenvironment interactions: dangerous liaisons. Adv Cancer Res 100:203–229PubMedCrossRef Witz IP (2008) Tumor-microenvironment interactions: dangerous liaisons. Adv Cancer Res 100:203–229PubMedCrossRef
9.
go back to reference Luo Y, Zhou H, Krueger J, Kaplan C, Lee SH, Dolman C, Markowitz D, Wu W, Liu C, Reisfeld RA, Xiang R (2006) Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest 116:2132–2141PubMedCrossRef Luo Y, Zhou H, Krueger J, Kaplan C, Lee SH, Dolman C, Markowitz D, Wu W, Liu C, Reisfeld RA, Xiang R (2006) Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest 116:2132–2141PubMedCrossRef
10.
go back to reference Zhang B, Bowerman NA, Salama JK, Schmidt H, Spiotto MT, Schietinger A, Yu P, Fu YX, Weichselbaum RR, Rowley DA, Kranz DM, Schreiber H (2007) Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med. 204:49–55PubMedCrossRef Zhang B, Bowerman NA, Salama JK, Schmidt H, Spiotto MT, Schietinger A, Yu P, Fu YX, Weichselbaum RR, Rowley DA, Kranz DM, Schreiber H (2007) Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med. 204:49–55PubMedCrossRef
11.
go back to reference Hagemann T, Lawrence T, McNeish I, Charles KA, Kulbe H, Thompson RG, Robinson SC, Balkwill FR (2008) “Re-educating” tumor-associated macrophages by targeting NF-kappaB. J Exp Med 205:1261–1268PubMedCrossRef Hagemann T, Lawrence T, McNeish I, Charles KA, Kulbe H, Thompson RG, Robinson SC, Balkwill FR (2008) “Re-educating” tumor-associated macrophages by targeting NF-kappaB. J Exp Med 205:1261–1268PubMedCrossRef
12.
go back to reference Murray F, Darzentas N, Hadzidimitriou A, Tobin G, Boudjogra M, Scielzo C, Laoutaris N, Karlsson K, Baran-Marzsak F, Tsaftaris A, Moreno C, Anagnostopoulos A, Caligaris-Cappio F, Vaur D, Ouzounis C, Belessi C, Ghia P, Davi F, Rosenquist R, Stamatopoulos K (2008) Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis. Blood 111:1524–1533PubMedCrossRef Murray F, Darzentas N, Hadzidimitriou A, Tobin G, Boudjogra M, Scielzo C, Laoutaris N, Karlsson K, Baran-Marzsak F, Tsaftaris A, Moreno C, Anagnostopoulos A, Caligaris-Cappio F, Vaur D, Ouzounis C, Belessi C, Ghia P, Davi F, Rosenquist R, Stamatopoulos K (2008) Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis. Blood 111:1524–1533PubMedCrossRef
13.
go back to reference Li Y, Lu J, Prochownik EV (2009) Modularity of the oncoprotein-like properties of platelet glycoprotein Ibalpha. J Biol Chem 284:1410–1418PubMedCrossRef Li Y, Lu J, Prochownik EV (2009) Modularity of the oncoprotein-like properties of platelet glycoprotein Ibalpha. J Biol Chem 284:1410–1418PubMedCrossRef
14.
go back to reference Potapov AP, Voss N, Sasse N, Wingender E (2005) Topology of mammalian transcription networks. Genome Inform 16:270–278PubMed Potapov AP, Voss N, Sasse N, Wingender E (2005) Topology of mammalian transcription networks. Genome Inform 16:270–278PubMed
15.
go back to reference Basak S, Hoffmann A (2008) Crosstalk via the NF-kappaB signaling system. Cytokine Growth Factor Rev 19:187–197PubMedCrossRef Basak S, Hoffmann A (2008) Crosstalk via the NF-kappaB signaling system. Cytokine Growth Factor Rev 19:187–197PubMedCrossRef
16.
go back to reference De Bosscher K, Vanden Berglu W, Haegeman G (2006) Cross-talk between nuclear receptors and nuclear factor kappaB. Oncogene 25:6868–6886PubMedCrossRef De Bosscher K, Vanden Berglu W, Haegeman G (2006) Cross-talk between nuclear receptors and nuclear factor kappaB. Oncogene 25:6868–6886PubMedCrossRef
17.
go back to reference Kim D, Kolch W, Cho KH (2009) Multiple roles of the NF-{kappa}B signaling pathway regulated by coupled negative feedback circuits. FASEB J, May 5, 23:1–7 Kim D, Kolch W, Cho KH (2009) Multiple roles of the NF-{kappa}B signaling pathway regulated by coupled negative feedback circuits. FASEB J, May 5, 23:1–7
18.
go back to reference Stelling J, Sauer U, Szallasi Z, Doyle FJ III, Doyle J (2004) Robustness of cellular functions. Cell 118:675–685PubMedCrossRef Stelling J, Sauer U, Szallasi Z, Doyle FJ III, Doyle J (2004) Robustness of cellular functions. Cell 118:675–685PubMedCrossRef
19.
go back to reference Pahler JC, Tazzyman S, Erez N, Chen YY, Murdoch C, Nozawa H, Lewis CE, Hanahan D (2008) Plasticity in tumor-promoting inflammation: impairment of macrophage recruitment evokes a compensatory neutrophil response. Neoplasia 10:329–340PubMed Pahler JC, Tazzyman S, Erez N, Chen YY, Murdoch C, Nozawa H, Lewis CE, Hanahan D (2008) Plasticity in tumor-promoting inflammation: impairment of macrophage recruitment evokes a compensatory neutrophil response. Neoplasia 10:329–340PubMed
20.
go back to reference Meyer S, Vogt T, Kunz-Schughart L, Bataille F, Reichle A, Hartmann A, Landthaler M, Sauter G, Wild PJ, Marx A, Andreesen R (2009) Cyclooxygenase2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) are stage-dependent prognostic markers of malignant melanoma. PPAR Res, in press Meyer S, Vogt T, Kunz-Schughart L, Bataille F, Reichle A, Hartmann A, Landthaler M, Sauter G, Wild PJ, Marx A, Andreesen R (2009) Cyclooxygenase2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) are stage-dependent prognostic markers of malignant melanoma. PPAR Res, in press
21.
go back to reference Reichle A, Vogt T, Coras B, Terheyden P, Neuber K, Trefzer U, Schultz E, Berand A, Brocker EB, Landthaler M, Andreesen R (2007) Targeted combined anti-inflammatory and angiostatic therapy in advanced melanoma: a randomized phase II trial. Melanoma Res 17:360–364PubMedCrossRef Reichle A, Vogt T, Coras B, Terheyden P, Neuber K, Trefzer U, Schultz E, Berand A, Brocker EB, Landthaler M, Andreesen R (2007) Targeted combined anti-inflammatory and angiostatic therapy in advanced melanoma: a randomized phase II trial. Melanoma Res 17:360–364PubMedCrossRef
22.
go back to reference Le Bitoux MA, Stamenkovic I (2008) Tumor-host interactions: the role of inflammation. Histochem Cell Biol 130:1079–1090PubMedCrossRef Le Bitoux MA, Stamenkovic I (2008) Tumor-host interactions: the role of inflammation. Histochem Cell Biol 130:1079–1090PubMedCrossRef
23.
24.
go back to reference Spemann H, Mangold H (2001) Induction of embryonic primordia by implantation of organizers from a different species. 1923. Int J Dev Biol 45:13–38PubMed Spemann H, Mangold H (2001) Induction of embryonic primordia by implantation of organizers from a different species. 1923. Int J Dev Biol 45:13–38PubMed
25.
go back to reference Chang JT, Carvalho C, Mori S, Bild AH, Gatza ML, Wang Q, Lucas JE, PottiA FPG, West M, Nevins JR (2009) A genomic strategy to elucidate modules ofoncogenic pathway signature networks. Mol Cell 10:104–114CrossRef Chang JT, Carvalho C, Mori S, Bild AH, Gatza ML, Wang Q, Lucas JE, PottiA FPG, West M, Nevins JR (2009) A genomic strategy to elucidate modules ofoncogenic pathway signature networks. Mol Cell 10:104–114CrossRef
26.
go back to reference Dobzhansky T, Schultz J (2004) Nothing in biology makes sense except in the light of evolution. Am Biol Teachers 35:125–129 Dobzhansky T, Schultz J (2004) Nothing in biology makes sense except in the light of evolution. Am Biol Teachers 35:125–129
27.
go back to reference Reichle A (2009) Tumor systems need to be rendered usable for a new action-theoretical abstraction: the starting point for novel therapeutic options. Current Cancer Therapy Reviews, in press Reichle A (2009) Tumor systems need to be rendered usable for a new action-theoretical abstraction: the starting point for novel therapeutic options. Current Cancer Therapy Reviews, in press
28.
go back to reference Wist AD, Berger SI, Iyengar R (2009) Systems pharmacology and genome medicine: a future perspective. Genome Med 1:11PubMedCrossRef Wist AD, Berger SI, Iyengar R (2009) Systems pharmacology and genome medicine: a future perspective. Genome Med 1:11PubMedCrossRef
29.
go back to reference Cohen AA, Geva-Zatorsky N, Eden E, Frenkel-Morgenstern M, Issaeva I, Sigal A, Milo R, Cohen-Saidon C, Liron Y, Kam Z, Cohen L, Danon T, Perzov N, Alon U (2008) Dynamic proteomics of individual cancer cells in response to a drug. Science 322:1511–1516PubMedCrossRef Cohen AA, Geva-Zatorsky N, Eden E, Frenkel-Morgenstern M, Issaeva I, Sigal A, Milo R, Cohen-Saidon C, Liron Y, Kam Z, Cohen L, Danon T, Perzov N, Alon U (2008) Dynamic proteomics of individual cancer cells in response to a drug. Science 322:1511–1516PubMedCrossRef
Metadata
Title
Principles of Modular Tumor Therapy
Authors
Albrecht Reichle
Gerhard C. Hildebrandt
Publication date
01-09-2009
Publisher
Springer Netherlands
Published in
Cancer Microenvironment / Issue Special Issue 1/2009
Print ISSN: 1875-2292
Electronic ISSN: 1875-2284
DOI
https://doi.org/10.1007/s12307-009-0023-x

Other articles of this Special Issue 1/2009

Cancer Microenvironment 1/2009 Go to the issue

News

Index

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine