Cancers of the aero-digestive system and side effects – Streinth Lab

Gastric & oesophagus cancers

Gastric cancer is the second most frequent cancer worlwide. The average survival rate at 5 year is dramatically low with less than 25% of the patients. It represents 5000 deaths every year in France.

Head and neck cancers

Head and neck cancers present also a reduced average survival rate at 5 years that is less than 50% accounting for about 5000 deaths every year. At present about 75% of the patients are males and with an aetiology involving life style (alcohol and smoking) as well as viruses.

Healthy tissues & sides effects

Side effects induced by cancer therapies affects different tissues leading often to halt of treatments and death in the worst situation. For instance, about 20% of cancer lethality is due to muscle atrophy, linked or not to malfunction of the digestive system, including the enteric nervous system.

Licona, C., Delhorme, J.-B., Riegel, G., Vidimar, V., Cerón-Camacho, R., Boff, B., … Gaiddon, C. (2020). Anticancer activity of ruthenium and osmium cyclometalated compounds: identification of ABCB1 and EGFR as resistance mechanisms. Inorganic Chemistry Frontiers, 7(3), 678–688. https://doi.org/10.1039/C9QI01148J

Miller, J. J., Blanchet, A., Orvain, C., Nouchikian, L., Reviriot, Y., Clarke, R. M., … Storr, T. (2019). Bifunctional ligand design for modulating mutant p53 aggregation in cancer. Chemical Science, 10(46), 10802–10814. https://doi.org/10.1039/c9sc04151f

Spaety, M.-E., Gries, A., Badie, A., Venkatasamy, A., Romain, B., Orvain, C., … Gaiddon, C. (2019). HDAC4 Levels Control Sensibility toward Cisplatin in Gastric Cancer via the p53-p73/BIK Pathway. Cancers, 11(11), 1747. https://doi.org/10.3390/cancers11111747

Coliat, P., Ramolu, L., Jégu, J., Gaiddon, C., Jung, A. C., & Pencreach, E. (2019). Constitutive or Induced HIF-2 Addiction is Involved in Resistance to Anti-EGFR Treatment and Radiation Therapy in HNSCC. Cancers, 11(10). https://doi.org/10.3390/cancers11101607

Liang, Y., Hou, L., Li, L., Li, L., Zhu, L., Wang, Y., … Meng, X. (2019). Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway. Oncogene. https://doi.org/10.1038/s41388-019-1035-8

Job, S., Reyniès, A. de, Heller, B., Weiss, A., Guérin, E., Macabre, C., … Jung, A. C. (2019). Preferential Response of Basal-Like Head and Neck Squamous Cell Carcinoma Cell Lines to EGFR-Targeted Therapy Depending on EREG-Driven Oncogenic Addiction. Cancers, 11(6). https://doi.org/10.3390/cancers11060795

Santoro, A., Vileno, B., Palacios, Ò., Peris-Díaz, M. D., Riegel, G., Gaiddon, C., … Faller, P. (2019). Reactivity of Cu(ii)-, Zn(ii)- and Fe(ii)-thiosemicarbazone complexes with glutathione and metallothionein: from stability to dissociation to transmetallation. Metallomics: Integrated Biometal Science, 11(5), 994–1004. https://doi.org/10.1039/c9mt00061e

Vidimar, V., Licona, C., Cerón-Camacho, R., Guerin, E., Coliat, P., Venkatasamy, A., … Gaiddon, C. (2019). A redox ruthenium compound directly targets PHD2 and inhibits the HIF1 pathway to reduce tumor angiogenesis independently of p53. Cancer Letters, 440–441, 145–155. https://doi.org/10.1016/j.canlet.2018.09.029

Miller, J. J., Orvain, C., Jozi, S., Clarke, R. M., Smith, J. R., Blanchet, A., … Storr, T. (2018). Multifunctional Compounds for Activation of the p53-Y220C Mutant in Cancer. Chemistry (Weinheim an Der Bergstrasse, Germany), 24(67), 17734–17742. https://doi.org/10.1002/chem.201802677

Lam, N. Y. S., Truong, D., Burmeister, H., Babak, M. V., Holtkamp, H. U., Movassaghi, S., … Hartinger, C. G. (2018). From Catalysis to Cancer: Toward Structure-Activity Relationships for Benzimidazol-2-ylidene-Derived N-Heterocyclic-Carbene Complexes as Anticancer Agents. Inorganic Chemistry, 57(22), 14427–14434. https://doi.org/10.1021/acs.inorgchem.8b02634

Minault, Q., Gaiddon, C., Veillon, F., & Venkatasamy, A. (2018). The Champagne sign. Abdominal Radiology (New York), 43(10), 2888–2889. https://doi.org/10.1007/s00261-018-1544-x

Chow, M. J., Babak, M. V., Tan, K. W., Cheong, M. C., Pastorin, G., Gaiddon, C., & Ang, W. H. (2018). Induction of the Endoplasmic Reticulum Stress Pathway by Highly Cytotoxic Organoruthenium Schiff-Base Complexes. Molecular Pharmaceutics, 15(8), 3020–3031. https://doi.org/10.1021/acs.molpharmaceut.8b00003

Gass, B., Marrer, E., Bara, S., Ligier, K., Molinié, F., Colonna, M., … Jégu, J. (2018). Use of a case-mix approach to study the trends in the incidence of second primary cancers. Annals of Epidemiology, 28(5), 322–327. https://doi.org/10.1016/j.annepidem.2018.02.008

Babak, M. V., Pfaffeneder-Kmen, M., Meier-Menches, S. M., Legina, M. S., Theiner, S., Licona, C., … Hartinger, C. G. (2018). Rollover Cyclometalated Bipyridine Platinum Complexes as Potent Anticancer Agents: Impact of the Ancillary Ligands on the Mode of Action. Inorganic Chemistry, 57(5), 2851–2864. https://doi.org/10.1021/acs.inorgchem.7b03210

Makarchuk, S., Beyer, N., Gaiddon, C., Grange, W., & Hébraud, P. (2018). Holographic Traction Force Microscopy. Scientific Reports, 8(1), 3038. https://doi.org/10.1038/s41598-018-21206-2

Manfredelli, S., Delhorme, J.-B., Venkatasamy, A., Gaiddon, C., Brigand, C., Rohr, S., & Romain, B. (2017). Could a Feeding Jejunostomy be Integrated into a Standardized Preoperative Management of Oeso-gastric Junction Adenocarcinoma? Annals of Surgical Oncology, 24(11), 3324–3330. https://doi.org/10.1245/s10434-017-5945-9

Chow, M. J., Alfiean, M., Pastorin, G., Gaiddon, C., & Ang, W. H. (2017). Apoptosis-independent organoruthenium anticancer complexes that overcome multidrug resistance: self-assembly and phenotypic screening strategies. Chemical Science, 8(5), 3641–3649. https://doi.org/10.1039/c7sc00497d

Estrada‐Montaño, A. S., Ryabov, A. D., Gries, A., Gaiddon, C., & Lagadec, R. L. (2017). Iron(III) Pincer Complexes as a Strategy for Anticancer Studies. European Journal of Inorganic Chemistry, 2017(12), 1673–1678. https://doi.org/10.1002/ejic.201601350

Licona, C., Spaety, M.-E., Capuozzo, A., Ali, M., Santamaria, R., Armant, O., … Gaiddon, C. (2017). A ruthenium anticancer compound interacts with histones and impacts differently on epigenetic and death pathways compared to cisplatin. Oncotarget, 8(2), 2568–2584. https://doi.org/10.18632/oncotarget.13711

Platet, N., Hinkel, I., Richert, L., Murdamoothoo, D., Moufok-Sadoun, A., Vanier, M., … Gross, I. (2017). The tumor suppressor CDX2 opposes pro-metastatic biomechanical modifications of colon cancer cells through organization of the actin cytoskeleton. Cancer Letters, 386, 57–64. https://doi.org/10.1016/j.canlet.2016.10.040

Khalil, G., Orvain, C., Fang, L., Barloy, L., Chaumont, A., Gaiddon, C., … Mobian, P. (2016). Monomeric Ti(iv)-based complexes incorporating luminescent nitrogen ligands: synthesis, structural characterization, emission spectroscopy and cytotoxic activities. Dalton Transactions (Cambridge, England: 2003), 45(47), 19072–19085. https://doi.org/10.1039/c6dt03477b

Chow, M. J., Babak, M. V., Wong, D. Y. Q., Pastorin, G., Gaiddon, C., & Ang, W. H. (2016). Structural Determinants of p53-Independence in Anticancer Ruthenium-Arene Schiff-Base Complexes. Molecular Pharmaceutics, 13(7), 2543–2554. https://doi.org/10.1021/acs.molpharmaceut.6b00348

Chow, M. J., Licona, C., Pastorin, G., Mellitzer, G., Ang, W. H., & Gaiddon, C. (2016). Structural tuning of organoruthenium compounds allows oxidative switch to control ER stress pathways and bypass multidrug resistance. Chemical Science, 7(7), 4117–4124. https://doi.org/10.1039/c6sc00268d

von Grabowiecki, Y., Abreu, P., Blanchard, O., Palamiuc, L., Benosman, S., Mériaux, S., … Gaiddon, C. (2016). Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63. ELife, 5, e10528. https://doi.org/10.7554/eLife.10528

Rico Bautista, H., Saavedra Díaz, R. O., Shen, L. Q., Orvain, C., Gaiddon, C., Le Lagadec, R., & Ryabov, A. D. (2016). Impact of cyclometalated ruthenium(II) complexes on lactate dehydrogenase activity and cytotoxicity in gastric and colon cancer cells. Journal of Inorganic Biochemistry, 163, 28–38. https://doi.org/10.1016/j.jinorgbio.2016.07.014

von Grabowiecki, Y., Licona, C., Palamiuc, L., Abreu, P., Vidimar, V., Coowar, D., … Gaiddon, C. (2015). Regulation of a Notch3-Hes1 pathway and protective effect by a tocopherol-omega alkanol chain derivative in muscle atrophy. The Journal of Pharmacology and Experimental Therapeutics, 352(1), 23–32. https://doi.org/10.1124/jpet.114.216879

Tasan, S., Licona, C., Doulain, P.-E., Michelin, C., Gros, C. P., Le Gendre, P., … Bodio, E. (2015). Gold-phosphine-porphyrin as potential metal-based theranostics. Journal of Biological Inorganic Chemistry: JBIC: A Publication of the Society of Biological Inorganic Chemistry, 20(1), 143–154. https://doi.org/10.1007/s00775-014-1220-8

Chow, M. J., Licona, C., Yuan Qiang Wong, D., Pastorin, G., Gaiddon, C., & Ang, W. H. (2014). Discovery and investigation of anticancer ruthenium-arene Schiff-base complexes via water-promoted combinatorial three-component assembly. Journal of Medicinal Chemistry, 57(14), 6043–6059. https://doi.org/10.1021/jm500455p

Klajner, M., Licona, C., Fetzer, L., Hebraud, P., Mellitzer, G., Pfeffer, M., … Gaiddon, C. (2014). Subcellular localization and transport kinetics of ruthenium organometallic anticancer compounds in living cells: a dose-dependent role for amino acid and iron transporters. Inorganic Chemistry, 53(10), 5150–5158. https://doi.org/10.1021/ic500250e

Boff, B., Gaiddon, C., & Pfeffer, M. (2013). Cancer cell cytotoxicity of cyclometalated compounds obtained with osmium(II) complexes. Inorganic Chemistry, 52(5), 2705–2715. https://doi.org/10.1021/ic302779q

Vidimar, V., Meng, X., Klajner, M., Licona, C., Fetzer, L., Harlepp, S., … Gaiddon, C. (2012). Induction of caspase 8 and reactive oxygen species by ruthenium-derived anticancer compounds with improved water solubility and cytotoxicity. Biochemical Pharmacology, 84(11), 1428–1436. https://doi.org/10.1016/j.bcp.2012.08.022

Ribeiro, N., Thuaud, F., Bernard, Y., Gaiddon, C., Cresteil, T., Hild, A., … Désaubry, L. (2012). Flavaglines as potent anticancer and cytoprotective agents. Journal of Medicinal Chemistry, 55(22), 10064–10073. https://doi.org/10.1021/jm301201z

Bergamo, A., Gaiddon, C., Schellens, J. H. M., Beijnen, J. H., & Sava, G. (2012). Approaching tumour therapy beyond platinum drugs: status of the art and perspectives of ruthenium drug candidates. Journal of Inorganic Biochemistry, 106(1), 90–99. https://doi.org/10.1016/j.jinorgbio.2011.09.030

Benosman, S., Meng, X., Von Grabowiecki, Y., Palamiuc, L., Hritcu, L., Gross, I., … Gaiddon, C. (2011). Complex regulation of p73 isoforms after alteration of amyloid precursor polypeptide (APP) function and DNA damage in neurons. The Journal of Biological Chemistry, 286(50), 43013–43025. https://doi.org/10.1074/jbc.M111.261271

Fetzer, L., Boff, B., Ali, M., Xiangjun, M., Collin, J.-P., Sirlin, C., … Pfeffer, M. (2011). Library of second-generation cycloruthenated compounds and evaluation of their biological properties as potential anticancer drugs: passing the nanomolar barrier. Dalton Transactions (Cambridge, England: 2003), 40(35), 8869–8878. https://doi.org/10.1039/c1dt10322a

Thuaud, F., Ribeiro, N., Gaiddon, C., Cresteil, T., & Désaubry, L. (2011). Novel flavaglines displaying improved cytotoxicity. Journal of Medicinal Chemistry, 54(1), 411–415. https://doi.org/10.1021/jm101318b

Klajner, M., Hebraud, P., Sirlin, C., Gaiddon, C., & Harlepp, S. (2010). DNA binding to an anticancer organo-ruthenium complex. The Journal of Physical Chemistry. B, 114(44), 14041–14047. https://doi.org/10.1021/jp1044783

Meng, X., Leyva, M. L., Jenny, M., Gross, I., Benosman, S., Fricker, B., … Gaiddon, C. (2009). A ruthenium-containing organometallic compound reduces tumor growth through induction of the endoplasmic reticulum stress gene CHOP. Cancer Research, 69(13), 5458–5466. https://doi.org/10.1158/0008-5472.CAN-08-4408

Ohtsubo, C., Shiokawa, D., Kodama, M., Gaiddon, C., Nakagama, H., Jochemsen, A. G., … Okamoto, K. (2009). Cytoplasmic tethering is involved in synergistic inhibition of p53 by Mdmx and Mdm2. Cancer Science, 100(7), 1291–1299. https://doi.org/10.1111/j.1349-7006.2009.01180.x

Benosman, S., Gross, I., Clarke, N., Jochemsen, A. G., Okamoto, K., Loeffler, J.-P., & Gaiddon, C. (2007). Multiple neurotoxic stresses converge on MDMX proteolysis to cause neuronal apoptosis. Cell Death and Differentiation, 14(12), 2047–2057. https://doi.org/10.1038/sj.cdd.4402216

Gross, I., Armant, O., Benosman, S., de Aguilar, J. L. G., Freund, J.-N., Kedinger, M., … Loeffler, J.-P. (2007). Sprouty2 inhibits BDNF-induced signaling and modulates neuronal differentiation and survival. Cell Death and Differentiation, 14(10), 1802–1812. https://doi.org/10.1038/sj.cdd.4402188

Lokshin, M., Li, Y., Gaiddon, C., & Prives, C. (2007). p53 and p73 display common and distinct requirements for sequence specific binding to DNA. Nucleic Acids Research, 35(1), 340–352. https://doi.org/10.1093/nar/gkl1047

Gross, I., Lhermitte, B., Domon-Dell, C., Duluc, I., Martin, E., Gaiddon, C., … Freund, J.-N. (2005). Phosphorylation of the homeotic tumor suppressor Cdx2 mediates its ubiquitin-dependent proteasome degradation. Oncogene, 24(54), 7955–7963. https://doi.org/10.1038/sj.onc.1208945

Gaiddon, C., Jeannequin, P., Bischoff, P., Pfeffer, M., Sirlin, C., & Loeffler, J. P. (2005). Ruthenium (II)-derived organometallic compounds induce cytostatic and cytotoxic effects on mammalian cancer cell lines through p53-dependent and p53-independent mechanisms. The Journal of Pharmacology and Experimental Therapeutics, 315(3), 1403–1411. https://doi.org/10.1124/jpet.105.089342

Di Scala, F., Dupuis, L., Gaiddon, C., De Tapia, M., Jokic, N., Gonzalez de Aguilar, J.-L., … Loeffler, J.-P. (2005). Tissue specificity and regulation of the N-terminal diversity of reticulon 3. The Biochemical Journal, 385(Pt 1), 125–134. https://doi.org/10.1042/BJ20040458

Gaiddon, C., Lokshin, M., Gross, I., Levasseur, D., Taya, Y., Loeffler, J.-P., & Prives, C. (2003). Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73. The Journal of Biological Chemistry, 278(30), 27421–27431. https://doi.org/10.1074/jbc.M300251200

Gaiddon, C., Lokshin, M., Ahn, J., Zhang, T., & Prives, C. (2001). A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain. Molecular and Cellular Biology, 21(5), 1874–1887. https://doi.org/10.1128/MCB.21.5.1874-1887.2001

González de Aguilar, J. L., Gordon, J. W., René, F., de Tapia, M., Lutz-Bucher, B., Gaiddon, C., & Loeffler, J. P. (2000). Alteration of the Bcl-x/Bax ratio in a transgenic mouse model of amyotrophic lateral sclerosis: evidence for the implication of the p53 signaling pathway. Neurobiology of Disease, 7(4), 406–415. https://doi.org/10.1006/nbdi.2000.0295

Gaiddon, C., Moorthy, N. C., & Prives, C. (1999). Ref-1 regulates the transactivation and pro-apoptotic functions of p53 in vivo. The EMBO Journal, 18(20), 5609–5621. https://doi.org/10.1093/emboj/18.20.5609

Gaiddon, C., Larmet, Y., Trinh, E., Boutillier, A. L., Sommer, B., & Loeffler, J. P. (1999). Brain-derived neurotrophic factor exerts opposing effects on beta2-adrenergic receptor according to depolarization status of cerebellar neurons. Journal of Neurochemistry, 73(4), 1467–1476.