Standardized Plant Immunomodulator Increases the Effect of MEK and BRAF Inhibitors with Clinical Benefit. Case Report of a Patient with Carcinoma in Biliary Duct

Abstract

Background: Targeting hyperactive mitogen-activated protein kinase (MAPK) signaling cascade has proven to be an effective treatment for a variety of different cancers. Using an important member of this cascade, namely MEK (mitogen-activated extracellular signal regulation kinase) inhibitors, the clinical responses are often transient and complete remission is rarely observed. It was shown that growth factor receptor signaling pathway inhibitors can increase the immune sensitivity of tumor cells but they can’t activate the down regulated immune effectors. Consequently, the combination of MAPK cascade signaling pathway inhibitors and the immune effectors activating immunomodulators may be a promising new strategy. Material and Methods: In a now 59 years old patient with inoperable (BRAF-mutant) low differentiated adenocarcinoma of biliary ducts after 30GY radiotherapy and two cycles (Gemcitabin+ Cisplatin) chemotherapy a rapid progression of lung, liver and brain metastases were by CT and MR established. A treatment was tarted with BRAF+MEK inhibitors (2x150 mg dabrafenib and 1 x 2 mg trametinib). These inhibitors were combined with daily 45 mg/kg rice bran arabinoxylan concentrate (using Biobran/MGN-3) which was shown to be a pathogenic associated molecular pattern (PAMP)-like molecule and can stimulate the type-1 innate immune cells against tumor cells. Results: After the chemotherapy and before the start of second-line treatment, the patient had a nearly terminal state of her rapidly progressive disease. Eight months after the combination of MEK / BRAF inhibitor and immunomodulator therapy nearly complete remissions of all metastases were established in CT and MR. Conclusion: This case report may support a hypothesis that MEK/BRAF inhibitors and type-1 immune cells activating immunomodulators together may synergistically inhibit the tumor growth. Further clinical investigations are necessary to clarify this question.