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

Cancer Microenvironment - Tập 8 - Trang 75-92 - 2015
Christina Hart1, Martin Vogelhuber1, Daniel Wolff1, Sebastian Klobuch1, Lina Ghibelli2, Jürgen Foell3, Selim Corbacioglu3, Klaus Rehe3, Guy Haegeman4, Simone Thomas1, Wolfgang Herr1, Albrecht Reichle1,5
1Department of Internal Medicine III, Haematology & Oncology, University Hospital of Regensburg, Regensburg, Germany
2Department of Biology, Universita’ di Roma Tor Vergata, Rome, Italy
3Department of Pediatrics, University Hospital of Regensburg, Regensburg, Germany
4University Gent, Ghent, Belgium
5Department of Internal Medicine III, Hematology and Oncology, University Hospital of Regensburg, Regensburg, Germany

Tóm tắt

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.

Tài liệu tham khảo

Paterlini-Bréchot P (2014) About seed and soil. Cancer Microenviron 7:91–93 Remon J, Majem M (2013) EGFR mutation heterogeneity and mixed response to EGFR tyrosine kinase inhibitors of non-small cell lung cancer: a clue to overcoming resistance. Trans Lung Cancer Res 2:445–448 Imielinski M, Berger AH, Hammerman PS et al (2012) Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150:1107–1120 Faber K, Bullinger L, Ragu C et al (2013) CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPARγ signaling. J Clin Invest 123:299–314 Hafner C, Toll A, Gantner S et al (2012) Keratinocytic epidermal nevi are associated with mosaic RAS mutations. J Med Genet 49:249–253 Hanahan D, Coussens LM (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21:309–322 Kallinowski F, Schlenger KH, Runkel S et al (1989) Blood flow, metabolism, cellular microenvironment, and growth rate of human tumor xenografts. Cancer Res 49:3759–3764 Pitteri SJ, Kelly-Spratt KS, Gurley KE et al (2011) Tumor microenvironment-derived proteins dominate the plasma proteome response during breast cancer induction and progression. Cancer Res 1:5090–5100 Bundscherer A, Hafner C (2010) Breathing new life into old drugs: Indication discovery by systems directed therapy. In: Reichle A (ed) From molecular to modular tumor therapy. Springer, Berlin, pp 483–503 Pantziarka P, Bouche G, Meheus L et al (2014) The repurposing drugs in oncology (ReDO) project. Ecancer Med Sci 8:442 Papi A, De Carolis S, Bertoni S et al (2014) PPARγ and RXR ligands disrupt the inflammatory cross-talk in the hypoxic breast cancer stem cells niche. J Cell Physiol 229(11):1595–1606 Glass CK, Ogawa S (2006) Combinatorial roles of nuclear receptors in inflammation and immunity. Nat Rev Immunol 6:44–55 Molecular cross-talk between nuclear receptors and nuclear factor-kB. Beck IME, Haegeman G, De Bosscher KA. Reichle A (ed.) From molecular to modular tumor therapy. Springer, Berlin, 191–242 Emmenegger U, Chow A, Bocci G (2010) The biomodulatory capacities of low-dose metronomic chemotherapy: Complex modulation of the tumor microenvironment. In: Reichle A (ed) From molecular to modular tumor therapy. Springer, Berlin, pp 243–262 Reichle A, Hildebrandt GC (2009) Principles of modular tumor therapy. Cancer Microenviron 2(Suppl 1):227–237 Reichle A, Vogt T (2008) Systems biology: a therapeutic target for tumor therapy. Cancer Microenviron 1:159–170 Mendoza-Parra MA, Gronemeyer H (2013) Genome-wide studies of nuclear receptors in cell fate decisions. Semin Cell Dev Biol 24:706–715 Reichle A. Including rationalizations of tumor-associated normative notions in pathophysiologic considerations: Communication-theoretical implications. Reichle A (ed) Evolution-adjusted tumor pathophysiology. Springer, Berlin, 289–299 Reichle A, Gerner C, Haegeman G (2013) Criticizable claims for the validity of communication acts in biological systems: Therapeutic implications in cancer. Reichle A (ed) Evolution-adjusted tumor pathophysiology. Springer, Berlin, 169–187 Reichle A, Grassinger J, Bross K et al (2007) C-reactive protein in patients with metastatic clear cell renal carcinoma: an Important biomarker for tumor-associated Inflammation. Biomark Insights 1:87–98 Walter B, Rogenhofer S, Vogelhuber M et al (2010) Modular therapy approach in metastatic castration-refractory prostate cancer. World J Urol 28:745–750 Vogelhuber M, Feyerabend S, Stenzl A, et al. (2014) Biomodulatory treatment of patients with castration-resistant prostate cancer: A phase II study of imatinib with pioglitazone, etoricoxib, dexamethasone and low-dose treosulfan. Cancer Microenviron Reichle A, Hart C, Grube M et al. (2012) Anti-inflammatory, immuno-modulatory and angiostatic treatment as third-line therapy for multiple myeloma (MM)—a combined treatment setting of lenalidomide with pioglitazone, dexamethasone and low-Dose treosulfan (phase I/II) Blood (ASH Annual Meeting Abstracts) 120:5029 Thomas S, Schelker R, Klobuch S et al (2015) Biomodulatory therapy induces complete molecular remission in chemorefractory acute myeloid leukemia. Haematologica 100(1):e4–e6 Ugocsai P, Wolff D, Menhart K (2015) Biomodulatory metronomic therapy induces PET negative remissionin chemo- and brentuximab-refractory Hodgkin disease. Br J Haematol. doi:10.1111/bjh.13480 Reichle A, Vogt T, Kunz-Schughart L et al (2005) Anti-inflammatory and angiostatic therapy in chemorefractory multisystem Langerhans’ cell histiocytosis of adults. Br J Haematol 128:730–732 Reichle A, Vogelhuber M, Vogt T et al. (2013) Long-term results of combined modularized, immune-modulatory, angiostatic, and antiinflammatory therapy in systemically pre-treated multi-systems Langerhans cell histiocytosis. Reichle A (ed) Evolution-adjusted tumor pathophysiology. Springer, Berlin, 35–45 Pahler JC, Tazzyman S, Erez N et al (2008) Plasticity in tumor promoting inflammation: impairment of macrophage recruitment evokes a compensatory neutrophil response. Neoplasia 10:329–340 Vogt T, Coras B, Hafner C et al (2006) Antiangiogenic therapy in metastatic prostate carcinoma complicated by cutaneous lupus erythematodes. Lancet Oncol 7:695–697 Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892 Vogelstein B, Papadopoulos N, Velculescu VE et al (2013) Cancer genome landscapes. Science 339:1546–1558 Tilg H, Vogel W, Dinarello CA (1995) Interferon-alpha induces circulating tumor necrosis factor receptor p55 in humans. Blood 85:433–435 Inoue K, Kawahito Y, Tsubouchi Y et al (2001) Expression of peroxisome proliferator-activated receptor gamma in renal cell carcinoma and growth inhibition by its agonists. Biochem Biophys Res Commun 287:727–732 Gerber SA, Pober JS (2008) IFN-alpha induces transcription of hypoxia-inducible factor-1alpha to inhibit proliferation of human endothelial cells. J Immunol 181:1052–1062 Berthold DR, Pond GR, Soban F et al (2008) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 26:242–245 Pleyer L, Burgstaller S, Girschikofsky M et al (2014) Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group. Ann Hematol 93:1825–1838 Luatti S, Castagnetti F, Marzocchi G et al (2012) Additional chromosomal abnormalities in Philadelphia-positive clone: adverse prognostic influence on frontline imatinib therapy: a GIMEMA Working Party on CML analysis. Blood 120:761–767 Yeung WWS, Ho MKC, Wong YH (2010) Functional Impacts of Signal Integration: Regulation of inflammation-related transcription factors by heterotrimeric G proteins. Reichle A (ed) From molecular to modular tumor therapy. Springer, Berlin, 161–189 Almendro V, Kim HJ, Cheng YK et al (2014) Genetic and phenotypic diversity in breast tumor metastases. Cancer Res 74:1338–1348 Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892 Yegnasubramanian S, Haffner MC, Zhang Y et al (2008) DNA hypomethylation arises later in prostate cancer progression than CpG island hypermethylation and contributes to metastatic tumor heterogeneity. Cancer Res 68:8954–8967 Galluzzi L, Vacchelli E, Bravo-San Pedro JM et al (2014) Classification of current anticancer immunotherapies. Oncotarget 5:12472–12508 Tosolini M, Kirilovsky A, Mlecnik B et al (2011) Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res 71:1263–1271 Giraldo NA, Becht E, Remark R et al (2014) The immune contexture of primary and metastatic human tumours. Curr Opin Immunol 27:8–15 Galon J, Costes A, Sanchez-Cabo F et al (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964s Ansell SM, Lesokhin AM, Borrello I et al (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319 Vasudev NS, Reynolds AR (2014) Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis 17:471–494 Reichle A and Hildebrandt GC (2010) The comparative uncovering of tumor systems biology by modularly targeting tumor-associated inflammation. Reichle A (ed) From molecular to modular tumor therapy. Springer, Berlin, 287–303 Khandelwal N, Breinig M, Speck T et al (2015) A high-throughput RNAi screen for detection of immune-checkpoint molecules that mediate tumor resistance to cytotoxic T lymphocytes. EMBO Mol Med 7:450–463 Reichle A (ed) (2013) Evolution adjusted tumor pathophysiology. Springer, Berlin Reichle A. Biomodulatory therapy approaches in renal clear cell carcinoma: A perspective (2013) Reichle A (ed) Evolution-adjusted tumor pathophysiology. Springer, Berlin, 91–100 Reichle A, Vogt T, Coras B et al (2007) Targeted combined anti-inflammatory and angiostatic therapy in advanced melanoma: a randomized phase II trial. Melanoma Res 17:360–364 Meyer S, Vogt T, Landthaler M (2009) Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage-Dependent Prognostic Markers of Malignant Melanoma. PPAR Res 2009:848645 Krug U, Koschmieder A, Schwammbach D et al (2012) Feasibility of azacitidine added to standard chemotherapy in older patients with acute myeloid leukemia--a randomised SAL pilot study. PLoS ONE 7:e52695 Schlenk RF, Fröhling S, Hartmann F et al (2004) Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia 18:1798–1803 Hartwell LH, Hopfield JJ, Leibler S et al (1999) From molecular to modular cell biology. Nature 402(6761 Suppl):C47–C52 Reichle A, Hildebrandt GC (2010) Uncovering tumor systems biology by biomodulatory therapy strategies. Reichle A (ed) From molecular to modular tumor therapy. Springer, Berlin, 287–303 Paulitschke V, Kunstfeld R, Gerner C. Secretome proteomics, a novel tool for biomarkers discovery and for guiding biomodulatory therapy approaches. Reichle A (ed) From molecular to modular tumor therapy. Springer, Berlin, 405–431