Related Experiment Video
Updated: Aug 15, 2025
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Severe colitis in patients with melanoma treated with BRAF/MEK inhibitors
Franck Carbonnel1,2,3, Emilie Routier4, Thierry Lazure5
1Service de Gastroentérologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, France.
Background And Aims:
Dual blockade of BRAF and MEK kinases is a standard of care for metastatic V600E/K BRAF mutant melanoma. This study reports the first systematic description of colitis due to BRAF and MEK inhibitors.
Methods:
We studied consecutive patients with melanoma, treated with BRAF and MEK inhibitors, who had colitis requiring hospitalisation. Electronic files were studied; endoscopic biopsies and colectomy specimens were read centrally.
Results:
Between January 2021 and March 2022, nine women and one man, aged 50-90 years, were studied. Nine patients received encorafenib and binimetinib; one patient received dabrafenib and trametinib. The main symptoms were diarrhoea, haematochezia, abdominal pain and intestinal obstruction. Blood tests showed anaemia, increased CRP and low serum albumin levels in most patients. All patients had ulcerations of the right colon with (2/10) or without (8/10) stenosis of the ileocecal valve, and 4/10 patients also had ulcerations distal to the right colon. Histopathological findings were suggestive of ischaemia and mild inflammation. Nine of the 10 patients discontinued BRAF/MEK inhibitors. Drugs were reintroduced in four patients, three of whom had a severe relapse of diarrhoea. Two patients required surgery and underwent intestinal resection. One patient died of enterocolitis.
Conclusion:
BRAF/MEK inhibitors can induce severe colitis characterised by ulcerations of the right colon.
Insights
BRAF and MEK inhibitors, used for melanoma, can cause severe colitis. This condition, characterized by right colon ulcerations, often requires drug discontinuation and can lead to serious complications.
Area of Science:
- Oncology
- Gastroenterology
- Pharmacology
Background:
- BRAF and MEK kinase inhibitors are standard treatment for metastatic BRAF V600E/K mutant melanoma.
- Colitis is a potential adverse event associated with BRAF and MEK inhibitor therapy.
Purpose of the Study:
- To systematically describe colitis induced by BRAF and MEK inhibitors.
- To characterize the clinical, endoscopic, and histopathological features of this adverse event.
Main Methods:
- Retrospective study of patients with melanoma treated with BRAF and MEK inhibitors who developed colitis requiring hospitalization.
- Centralized review of electronic records, endoscopic biopsies, and colectomy specimens.
Main Results:
- Ten patients (9 female, 1 male; aged 50-90) developed colitis.
- Symptoms included diarrhea, hematochezia, abdominal pain, and obstruction; histopathology suggested ischemia and inflammation.
- Right colon ulcerations were observed in all patients, with ileocecal valve stenosis in 20%.
Conclusions:
- BRAF/MEK inhibitors can induce severe colitis with characteristic right colon ulcerations.
- Discontinuation of inhibitors is often necessary, with a high rate of relapse upon reintroduction.
- This colitis can lead to significant morbidity, including surgery and mortality.
Related Concept Videos
01:29Drugs for Treatment of Ulcerative Colitis in IBD
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
01:21Inflammatory Bowel Disease V: Surgical Management
Here are some common surgical interventions for IBD:
01:29Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...