Dataset Information

A Case Presentation of a Patient with Microsatellite Instability and BRAF Mutant Metastatic Colon Cancer and Bibliography Update.

ABSTRACT: This is a case of a patient who presented to the emergency department with acute abdominal pain due to bowel obstruction. An extended right hemicolectomy with ileosigmoid anastomosis due to an obstructing mass on the splenic flexure was urgently performed. During operation, liver and peritoneal lesions were detected and samples were also sent for histological analysis. Pathology report was consistent with poorly differentiated mucinous adenocarcinoma with signet ring cells; peritoneal lesions were confirmed histologically as metastatic. Genetic testing revealed the BRAFV600E mutation and mismatch repair deficiency (dMMR). After progressing on 1st line chemotherapy, the patient has a continuing and long-lasting partial response to 2nd line treatment with pembrolizumab.

SUBMITTER: Thomopoulou K

PROVIDER: S-EPMC6398041 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Case Presentation of a Patient with Microsatellite Instability and BRAF Mutant Metastatic Colon Cancer and Bibliography Update.

Thomopoulou K K Tzardi M M Mavroudis D D Souglakos I I

Case reports in oncological medicine 20190217

This is a case of a patient who presented to the emergency department with acute abdominal pain due to bowel obstruction. An extended right hemicolectomy with ileosigmoid anastomosis due to an obstructing mass on the splenic flexure was urgently performed. During operation, liver and peritoneal lesions were detected and samples were also sent for histological analysis. Pathology report was consistent with poorly differentiated mucinous adenocarcinoma with signet ring cells; peritoneal lesions we ...[more]

PMID: 30911424

Similar Datasets

Project description:Colorectal cancer patients with BRAF-mutant tumors have a more aggressive, rapidly progressing disease that is in critical need of novel therapeutic approaches. Indeed, whereas the median overall survival (OS) of colorectal cancer (CRC) patients receiving standard-of-care therapy is approximately two years or more if their tumors express wild-type BRAF and wild-type KRAS, median OS is less than twelve months with tumors expressing V600E-mutant BRAF and wild-type KRAS. Pro-apoptotic receptor agonists are a class of biologic agents under development to induce tumor-specific apoptosis and are being combined with classical chemotherapy or targeted agents in clinical trials. Herein, we present the case of a patient with bulky V600E-mutant BRAF hepatic flexure colon carcinoma, treated initially with FOLFOX plus bevacizumab neoadjuvant therapy and surgery. The patient had a rapid tumor relapse with metastatic disease to the liver and lung, and was enrolled in a phase 1b open-label clinical study, where he received the FOLFIRI regimen in combination with the pro-apoptotic receptor agonist dulanermin (rhApo2L/TRAIL). The patient maintained stable disease through 25 doses administered every two weeks before his disease progressed. After coming off study, the patient underwent surgical debulking and received intraperitoneal hyperthermic chemotherapy. He subsequently relapsed and was treated with FOLFIRI plus cetuximab. At the time of this report, the patient remains on active treatment. It is unclear what effect dulanermin may have had on the course of his disease, but it is noteworthy that the patient remained on FOLFIRI plus dulanermin therapy for a period that exceeded the median OS for patients with advanced, aggressive BRAF-mutant CRC. It is also noteworthy that at the time of this report the patient's overall survival since diagnosis has exceeded 30 months, which is beyond what is generally observed even for patients with CRC harboring wild-type BRAF and wild-type KRAS.

Project description:BackgroundIn v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutant colorectal cancer (CRC), encorafenib-cetuximab has been established as standard second-line therapy, but not all patients respond and the duration of response is relatively short. Overcoming intrinsic or acquired resistance to BRAF/EGFR inhibitors is crucial for enhancing treatment outcomes in metastatic BRAF-mutated CRC. The aim of the study is to investigate the resistance mechanisms in BRAF-mutant CRC patient refractory to BRAF/EGFR targeted therapy.MethodsWe established patient-derived cells (PDCs) from a patient with BRAF/PTEN-mutant metastatic colon cancer who progressed rapidly on encorafenib plus cetuximab. To explore potential treatment options for inherent resistance caused by simultaneous PTEN mutation in BRAF-mutated CRC, we conducted cell viability assays using PDCs treated with encorafenib-cetuximab in combination with a cyclin-dependent kinase-4 and 6 (CDK4/6) inhibitor.ResultsThe patient's tumor had concurrent PTEN loss-of-function alteration at diagnosis and PDCs were generated from ascites after resistance to the BRAF/EGFR inhibitor. The PDCs were resistant to the encorafenib-cetuximab combination even at a high concentration of cetuximab (up to 500 µg/mL). Adding the CDK4/6 inhibitor, ribociclib, to encorafenib-cetuximab showed a synergistic effect in a proliferation assay. Ribociclib plus encorafenib-cetuximab represented a significantly lower expression of Ki-67 compared to the dual combination alone. An MTS assay showed that triplet therapy with ribociclib, encorafenib, and cetuximab suppressed cell viability more efficiently than the two-drug combinations. Investigating the combined effect of triplet therapy using the calculated combination index (CI) showed that ribociclib had a synergistic effect with encorafenib-cetuximab when applied to PDCs with a concurrent BRAF/PTEN mutation.ConclusionsOur results suggest that combining the CDK4/6 inhibitor with the BRAF/EGFR inhibitor might be a novel treatment strategy for concomitant BRAF and PTEN-mutant CRC.

Dataset Information

A Case Presentation of a Patient with Microsatellite Instability and BRAF Mutant Metastatic Colon Cancer and Bibliography Update.

Publications

A Case Presentation of a Patient with Microsatellite Instability and BRAF Mutant Metastatic Colon Cancer and Bibliography Update.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets