Detecting and targeting tumor relapse by its resistance to innate effectors at early recurrence
Timothy Kottke,Nicolas Boisgerault,Rosa Maria Diaz,Oliver Donnelly,Diana Rommelfanger-Konkol,Jose S. Pulido,Jill Thompson,Debabrata Mukhopadhyay,Roger Kaspar,Matthew C. Coffey,Hardev Pandha,Alan Melcher,Kevin J. Harrington,Peter Selby,Richard G. Vile,Richard G. Vile +15 more
TLDR
Premature induction of recurrence resensitized MRD to the primary therapy, suggesting a possible paradigm shift for clinical treatment of dormant disease in which the current expectant approach is replaced with active attempts to uncover MRD before evolution of the escape phenotype is complete.Abstract:
Tumor recurrence represents a major clinical challenge. Our data show that emergent recurrent tumors acquire a phenotype radically different from that of their originating primary tumors. This phenotype allows them to evade a host-derived innate immune response elicited by the progression from minimal residual disease (MRD) to actively growing recurrence. Screening for this innate response predicted accurately in which mice recurrence would occur. Premature induction of recurrence resensitized MRD to the primary therapy, suggesting a possible paradigm shift for clinical treatment of dormant disease in which the current expectant approach is replaced with active attempts to uncover MRD before evolution of the escape phenotype is complete. By combining screening with second-line treatments targeting innate insensitivity, up to 100% of mice that would have otherwise relapsed were cured. These data may open new avenues for early detection and appropriately timed, highly targeted treatment of tumor recurrence irrespective of tumor type or frontline treatment.read more
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Genetically engineered mouse models in oncology research and cancer medicine.
TL;DR: GEMMs have been used to validate candidate cancer genes and drug targets, assess therapy efficacy, dissect the impact of the tumor microenvironment, and evaluate mechanisms of drug resistance.
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Inflammation and Cancer
TL;DR: Differences between acute and chronic inflammation in the context of cancer, how each state arises, and how each can be manipulated for development of new cancer therapeutics are outlined.
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Promising Targets for Cancer Immunotherapy: TLRs, RLRs, and STING-Mediated Innate Immune Pathways.
TL;DR: New data suggest that activation of the tolerant innate immune system in cancer patients is able, at least partially, to counteract tumor-induced immunosuppression, which indicates triggering of the innate immune response as a novel immunotherapeutic strategy may result in improved therapeutic outcomes for cancer patients.
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IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting.
Kazuyoshi Takeda,Masafumi Nakayama,Yoshihiro Hayakawa,Yuko Kojima,Hiroaki Ikeda,Naoko Imai,Naoko Imai,Kouetsu Ogasawara,Ko Okumura,David Thomas,Mark J. Smyth,Mark J. Smyth,Mark J. Smyth +12 more
TL;DR: It is shown that exposure of tumours to IFN-γ-producing antigen-specific CTLs in vivo results in copy-number alterations (CNAs) associated with DNA damage response and modulation of DNA editing/repair gene expression, which suggest that enhanced genetic instability might be one of the mechanisms by which C TLs and IFn-γ immunoedits tumours alter their immune resistance as a result of genetic evolution.
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A biodegradable thermo-responsive hybrid hydrogel: therapeutic applications in preventing the post-operative recurrence of breast cancer
Ying Qu,Bing Yang Chu,Jinrong Peng,Jinfeng Liao,Ting Ting Qi,Kun Shi,Xiao Ning Zhang,Yu Quan Wei,Zhiyong Qian +8 more
TL;DR: A thermoresponsive hydrogel containing gold nanorods can reduce breast cancer recurrence by delivering thermotherapeutic and chemotherapeutic drug.
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