Anticancer research · 2025
Bone Toxicity Case Report Combining Encorafenib, Cetuximab and WNT974 in a Phase I Trial.
Клинический случайСтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
VAN Bussel Mark T J, Bravenboer Nathalie, Essen Huib VAN, Snaebjornsson Petur, Appelman-Dijkstra Natasha M, Schellens Jan Hm, Opdam Frans L
Аннотация
BACKGROUND/AIM: More than 90% of colorectal cancers (CRC) have alterations in WNT signaling. Eight to ten percent of patients with metastatic Kirsten rat sarcoma virus - wild type (KRAS-WT) CRC have B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF) mutations and do not benefit from epidermal growth factor receptor (EGFR) antibodies. The addition of a porcupine inhibitor could increase the response rate in patients with BRAFV600E-mutated KRAS-WT metastatic CRC (mCRC) with WNT pathway alterations.
PATIENTS AND METHODS: We report two cases of severe bone toxicities during treatment with the BRAF inhibitor encorafenib, the EGFR-targeting monoclonal antibody cetuximab, and the porcupine inhibitor WNT974 in the phase 1B study NCT02278133.
RESULTS: Patient 1, a 66-year-old man with BRAFV600E-mutated KRAS-WT mCRC and an RNF43 mutation, developed multiple rib fractures and collapse of thoracic vertebrae 10 and 11. Autopsy revealed no metastases at fracture sites; histology demonstrated a thin, porous cortex and poor trabecular bone structure. Immunohistochemistry assessed key WNT pathway components. Patient 2, a 70-year-old man with similar mutations, experienced a toe fracture, multiple rib fractures, osteopenia, and altered bone biomarkers indicative of disrupted bone turnover.
CONCLUSION: The two patients described developed severe bone toxicities including rib fractures, a toe fracture, osteoporotic thoracic collapses, hypercalcemia, and alternated bone biomarkers. These cases highlight the potential skeletal risks associated with dual MAPK and WNT pathway inhibition.
PATIENTS AND METHODS: We report two cases of severe bone toxicities during treatment with the BRAF inhibitor encorafenib, the EGFR-targeting monoclonal antibody cetuximab, and the porcupine inhibitor WNT974 in the phase 1B study NCT02278133.
RESULTS: Patient 1, a 66-year-old man with BRAFV600E-mutated KRAS-WT mCRC and an RNF43 mutation, developed multiple rib fractures and collapse of thoracic vertebrae 10 and 11. Autopsy revealed no metastases at fracture sites; histology demonstrated a thin, porous cortex and poor trabecular bone structure. Immunohistochemistry assessed key WNT pathway components. Patient 2, a 70-year-old man with similar mutations, experienced a toe fracture, multiple rib fractures, osteopenia, and altered bone biomarkers indicative of disrupted bone turnover.
CONCLUSION: The two patients described developed severe bone toxicities including rib fractures, a toe fracture, osteoporotic thoracic collapses, hypercalcemia, and alternated bone biomarkers. These cases highlight the potential skeletal risks associated with dual MAPK and WNT pathway inhibition.