Species differences in tumour responses to cancer chemotherapy

Abstract

Despite advances in chemotherapy, radiotherapy and targeted drug development, cancer remains a disease of high morbidity and mortality. The treatment of human cancer patients with chemotherapy has become commonplace and accepted over the past 100 years. In recent years, and with a similar incidence of cancer to people, the use of cancer chemotherapy drugs in veterinary patients such as the dog has also become accepted clinical practice. The poor predictability of tumour responses to cancer chemotherapy drugs in rodent models means that the standard drug development pathway is costly, both in terms of money and time, leading to many drugs failing in Phase I and II clinical trials. This has led to the suggestion that naturally occurring cancers in pet dogs may offer an alternative model system to inform rational drug development in human oncology. In this review, we will explore the species variation in tumour responses to conventional chemotherapy and highlight our understanding of the differences in pharmacodynamics, pharmacokinetics and pharmacogenomics between humans and dogs. Finally, we explore the potential hurdles that need to be overcome to gain the greatest value from comparative oncology studies.

Cloning, localization and focus formation at DNA damage sites of canine Ku70

“…Therefore, compared to other animals, canines have been proposed to be a good model for cancer research, and development of therapeutic drugs and next-generation radiotherapies [10, 25, 30]. Previous studies in human and rodent cells have shown that the localization and function of Ku70 at DSB sites might play a crucial role in modulating the NHEJ repair pathway [3, 14, 20, 26, 28].…”

Tiermedizinische Publikationen in Complementary Medicine Research

“…Vielleicht sind diese Artikel auch für Humanmediziner lesenswert, werden doch spontan beim Hund auftretende Tumoren immer wieder (wenn auch kontrovers) als «Modell» für humane Tumorerkrankungen diskutiert [13]. Zudem ist in der Tiermedizin an der Tagesordnung, was in der Humanmedizin selten bis undenkbar ist, nämlich der ausdrückliche Wunsch des Tierbesitzers (mithin nach operativer Entfernung des Tumors), auf weitere Therapien zu verzichten.…”

“…Man mag das verteufeln oder für eine herausragende Errungenschaft der modernen medizinischen Forschung halten. Aber selbst wenn der Nutzten solcher Studien nicht unumstritten ist [13]: Fakt ist, dass derzeit die rechtlichen Rahmenbedingungen solche Versuche schlicht unumgänglich machen und dass überwiegend diese Art von Forschung Erkenntnisse über grundsätzliche Wirkmechanismen ermöglicht.…”

“…Hierzu seien (fast) zum Schluss noch 2 Originalzitate angeführt. In der bereits erwähnten aktuellen Übersichtsarbeit zur Dokumentation von Nebenwirkungen in prospektiven klinischen Studien zum Einsatz der Chemotherapie bei «Companion Animals» kam Giuffrida [9] -nachdem sie zeigen konnte, dass in den meisten Studien Nebenwirkungen nur unzureichend dokumentiert und diskutiert wurden -zu folgendem Schluss: «When adverse events are not adequately surveyed or transparently reported in trial publications, investigators, clinicians, and other stakeholders can overestimate the benefits of a treatment relative to its harms.» Lawrence et al [13] trafen in einer weiteren aktuellen vergleichenden Über-sichtsarbeit zur Chemotherapie in der Veterinär-und Humanonkologie folgende konklusive Aussage: «At least for the foreseeable future, for the veterinary oncologist, and irrespective of apparent differences in tumor responses across species, the focus for veterinary patients such as the dog is maintaining or improving an excellent quality-of-life, as perceived by the owner and/or attending veterinary clinician.» Die Misteltherapie könnte, nicht zuletzt aufgrund ihrer guten Verträglichkeit, hierzu einen Beitrag leisten.…”

Crosstalk between E2F1 and P53 transcription factors in doxorubicin-induced DNA damage: evidence for preventive/protective effects of silymarin

“…Among the other non‐contagious diseases, cancer seems to be a leading cause of morbidity and mortality, and some estimation has predicted that there will be 13.1 million deaths because of cancer in 2030 . Chemotherapy is the most popular therapeutic strategy for patients with cancer . However, as most of the currently used chemotherapeutic agents do have severe toxic effects, which may cause limitations in their usage, it would be worthwhile to consider having therapeutic agents that simultaneously have improved efficacy and less toxicity.…”