دانلود کتاب Novel Sensitizing Agents for Therapeutic Anti-EGFR Antibodies

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Front Cover Novel Sensitizing Agents for Therapeutic Anti-EGFR Antibodies Copyright Cover Image Insert Aims and Scope of Series ``Breaking Tolerance to Antibody-Mediated Immunotherapy´´ About the Series Editor Aims and Scope of Volume About the Volume Editor Preface Contents Contributors Chapter 1: Current status of anti-EGFR agents Introduction Targeting EGFR Novel EGFR targeting strategies Conclusions References Chapter 2: Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab Introduction EGFR biology The role of EGFR in human cancer The function of EGFR-targeted antibodies Cetuximab in the clinic Mechanisms of resistance to EGFR-targeted antibodies EGFR mutations EGFR gene copy number as a predictor of response EGFR ligand state KRAS mutations as a predictor of response BRAF mutation as a predictor of response Mechanisms of resistance against EGFR-targeted antibodies Angiogenesis Disorders of EGFR internalization and degradation Oncogenic shift Subcellular localization of EGFR Epithelial cells transform into mesenchymal cells Constitutive activation of EGFR downstream effector molecules Increased expression of HER family growth factors Concluding remarks References Chapter 3: MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extrace Introduction EGFR ECD mutations do not affect ligand-receptor binding but do affect antibody-receptor binding MM-151 can inhibit the growth of LIM1215 cells overexpressing EGFR ECD mutants MM-151 can inhibit the growth of cetuximab-resistant clones in spontaneous models MM-151 reduced the frequency of EGFR-ECD allele mutations Discussion References Further reading Chapter 4: Sym004 anti-EGFR antibody mixture overcomes resistance to anti-EGFR antibodies in metastatic colorectal cancer EGFR and CRC SYM004 compared with cetuximab Cell proliferation and induction of apoptosis EGFR-dependent intracellular signaling/MET activation and ERBB2 amplification Tumor xenograft models of human colorectal cancer HER2 Final thoughts and future directions References Chapter 5: Broad RTK-targeted therapy overcomes molecular heterogeneity-driven resistance to cetuximab via vectored immun ... Study on the related functional signaling network pathway based on the drug resistance of targeted monoclonal antibodies in CRC Phased therapeutic strategy of antibody transformation in vivo based on VIP background In vivo experiments were conducted to characterize the relationship between pathway crosstalk of key gene effectors and dru ... Cross design and effect presentation of VIP therapeutic drugs and carriers Final summary and assumption References Chapter 6: Pan-HER, an antibody mixture, simultaneously targeting EGFR, HER2, and HER3 effectively overcomes resistance References Chapter 7: Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through dis ... Introduction Design and characterization of four-in-one antibodies Four-in-one antibodies can effectively inhibit EGFR, HER2, HER3, and VEGFR2 The four-in-one antibody has excellent antitumor activity both in vitro and in vivo Only four-in-one antibodies interfere with HER/MET crosstalk MET/HER signaling is critical for resistance to HER-targeted therapy Four-in-one antibodies can overcome resistance to HER therapy Discussion References Chapter 8: Overcoming acquired resistance to cetuximab by combining EGFR- and HER3-neutralizing monoclonal antibodies EGFR inhibitor tolerance is related to both EGFR and HER3, which MEHD7945A completely targets MEHD7945A inhibits the growth of two tumor cell lines that are resistant to cetuximab MEHD7945A inhibits the growth of human tumor xenografts that are resistant to EGFR inhibitors MEHD7945A inhibits radiation-induced survival and overcomes cross-resistance to radiation mAb33: A neutralizing anti-HER3 antibody that prevents resistance to an EGF kinase inhibitor Combining osimertinib with mAb33 overcomes resistance by upregulating HER3 and inhibiting the release of the soluble extrac ... Combination of mAb33, cetuximab, and osimertinib inhibits growth of human tumor xenografts by simultaneously inhibiting oth ... The drug combination comprising mAb33 delays relapse of a model derived from a patients metastatic lesion Discussion References Chapter 9: Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiat HER3 is an essential regulatory target for acquired drug resistance The mechanism of MEHD7945A in overcoming acquired drug resistance through tumor xenografts and cells Study on the mechanism of MEHD7945A in radiation-damaged cells Final thoughts and future directions References Chapter 10: Targeting ERBB2 overcomes resistance to the anti-EGFR therapeutic antibody cetuximab Introduction ERBB2 amplification mediates cetuximab resistance through Erk1/2 signaling Heregulin activates ERBB2 signaling and mediates resistance to cetuximab without ERBB2 amplification 611-CTF, a C-terminal fragment of HER2, is phosphorylated in cetuximab-resistant cells Targeting ERBB2 signaling overcomes resistance to cetuximab: Preclinical studies Dual inhibition of ERBB2 and EGFR in cetuximab-resistant patients: Clinical trials Conclusion References Chapter 11: CT16: A dual antibody targeting both EGFR and Notch suppresses EGFR blockage and radiation resistance by decrea Introduction Combined use of EGFR inhibitors and irradiation can promote EMT and stem cell-like properties in NSCLC cells Enrichment of the ALDH+ cell population depends on Notch2/3 receptors Dual blockade of EGFR and Notch2/3 inhibits resistance to EGFR inhibitors in vitro Dual blockade of EGFR and Notch2/3 inhibits resistance to EGFR inhibitors in vivo CT16 enhances the radiosensitivity of cancer cells and reduces the ALDH+ cell populations CT16 can reduce the proliferation of tumor cells and shows good antitumor activity Dual blockade of EGFR and Notch2/3 reduces the number of CSCs and delays tumor recurrence after radiotherapy Discussion References Chapter 12: BET inhibition overcomes receptor tyrosine kinase-mediated cetuximab resistance in HNSCC Introduction The HNSCC model of acquired cetuximab resistance relies on surrogate RTK activity Pharmacological inhibition of BET family members overcame cetuximab resistance in vitro Blocking BET can inhibit the expression of RTK in the HNSCC model of cetuximab RTK overexpression mediates resistance to cetuximab and BET inhibition BET blocking prevents the acquisition of cetuximab resistance in the PDX model of HNSCC patients Expression of RTK and BRD4 genes in a clinical cohort of HNSCC Conclusion References Chapter 13: Dual inhibition of EGFR and c-Src by cetuximab and dasatinib combined with FOLFOX chemotherapy in patien Combination synergistic chemotherapy of mCRC treatment Phase IB: Safety and efficacy Phase II: The role of KRAS mutation RAS amplification and KRAS mutation IBD and KRAS-amplified mCRC Discussion and future directions References Chapter 14: A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors References Chapter 15: Use of MET kinase inhibitors to overcome cetuximab resistance in colorectal cancer Introduction EGFR and MET are coexpressed in a genotypically diverse panel of cetuximab-sensitive CRC cell lines Combined activation of EGFR and MET enhances CRC cell proliferation by augmenting the activation of AKT and MAPK HGF induces resistance to cetuximab through MET activation HGF rescues CRC cells from cetuximab-induced G1 arrest HGF rescued the apoptosis of DiFi cells induced by cetuximab HGF rescue occurs via MET-dependent activation of AKT and MAPK Discussion References Chapter 16: EGFR- and VEGF(R)-targeted small molecules show synergistic activity in colorectal cancer models refractory t ... An important oncogenic signaling pathway: Intracellular signal transduction Mechanistic differences and activity comparison between TKIs and mAbs Final thoughts and future directions References Chapter 17: Antitumor activity of the VEGFR inhibitor ZD6474 in human cancer cells resistant to anti-EGFR therapy Introduction ZD6474 efficiently inhibited the growth of EGFR-resistant tumors via inhibition of VEGFR The combination of ZD6474 and cetuximab displayed a synergistic antitumor effect against multiple cancer cell lines Discussion References Chapter 18: Antibody-mediated delivery of anti-KRAS-siRNA overcomes therapy resistance in colon cancer Introduction Generation and characterization of KRAS-siRNA-anti-EGFR antibody complexes In vitro validation of KRAS-siRNA-anti-EGFR antibody complexes: KRAS silencing and tumor inhibitory activity In vivo antitumor effect of the cetuximab-KRAS-esiRNA complex Final thoughts and future directions References Chapter 19: Primary and acquired resistance of colorectal cancer cells to anti-EGFR antibodies converge on MEK/ERK pathwa References Chapter 20: MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS-mutated colorectal cancer that is ... The status of K-RAS mutations is the key influencing factor in determining cetuximab resistance sensitivity Efficacy in the ERK pathway, proliferation, transformation, and tumor growth in cetuximab-resistant tumor cells caused by K ... The development of MEK inhibitors and the discovery of their mechanism of action Final thoughts and future directions References Chapter 21: EGFR/JIP-4/JNK2 signaling attenuates cetuximab-mediated radiosensitization of squamous cell carcinoma cells 3-Dimensional (3D) extracellular matrix (ECM) for studying how HNSCC cells grow in vivo Growth conditions play an important role in EGFR phosphorylation and signaling Cytotoxicity and radiosensitizing potential of cetuximab Phosphoproteome modifications after cetuximab-mediated EGFR inhibition JNK2 depletion enhances cetuximab-induced radiosensitization JIP-4 connects EGFR to JNK2 Discussion References Chapter 22: EGFR/Notch antagonists enhance the response to inhibitors of the PI3K-Akt pathway by decreasing t References Chapter 23: Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab Introduction SLC1A5 is overexpressed in cancer tissues of cetuximab-resistant CRC patients SLC1A5 promotes the proliferation of CRC both in vitro and in vivo Targeting SLC1A5 significantly enhanced the inhibitory effect of cetuximab on CRC proliferation Targeting SLC1A5 increases ubiquitin-proteasome pathway-mediated EGFR degradation Inhibition of SLC1A5 induces DNA damage in CRC cells Discussion References Further reading Chapter 24: Targeting of PYK2 synergizes with EGFR antagonists in basal-like TNBC and circumvents HER3-associated resis References Chapter 25: Overcoming acquired resistance to EGFR-targeted therapy by regulating autophagy Overlap between EGFR and autophagy regulatory signaling Autophagy facilitates tumor resistance to targeted biological therapies Targeting autophagy helps solve the problem of resistance to anti-EGFR treatments miRNAs and EVs regulate both autophagy and the response of cancer cells to anti-EGFR treatments Antiautophagic peptides that modulate the effect of anti-EGFR therapy on tumor cells Discussion References Chapter 26: Hedgehog signaling alters reliance on EGF receptor signaling and mediates anti-EGFR therapeutic resistance in ... Introduction Crosstalk between EGFR and HhP in HNSCC Combination of cetuximab and IPI-926 in preclinical models Conclusion References Chapter 27: Novel Toll-like receptor 9 agonist induces epidermal growth factor receptor (EGFR) inhibition and synergistic ... The ability of CpG DNA to affect tumor growth related to EGFR pathways IMO combined with cetuximab inhibits the expression and angiogenesis of signaling proteins and causes potent antitumor activity The in vitro effect of IMO is not obvious Cooperation of IMO and the EGFR tyrosine kinase inhibitor gefitinib has a combined effect IMO has no inhibitory effect on the growth of cetuximab-resistant GEO-CR xenografts but still cooperates with cetuximab Tumor xenografts can achieve eradication under administration of IMO in combination with cetuximab and irinotecan Discussion References Chapter 28: Targeted cancer therapy: The future of drug combinations Introduction Molecular bases of cancer and growth factor pathway Cancer therapy and mechanisms underlying drug action/resistance Therapeutic mAbs: Mechanisms of action and combinations Future expectations regarding the PD-1/PD-L1 pathways A different way of classifying tumor resistance Does endocytosis/EGFR downregulation explain resistance to mAbs? Conclusion and future tendencies References Index Back Cover