Background:

Targeting hyperactive mitogen-activated protein kinase (MAPK) signaling cascade has proven to be an effective treatment for a variety of differentcancers. Using an important member of this cascade, namely MEK (mitogen activated extracellular signal regulation kinase) inhibitors, the clinical responses areoften transient and complete remission is rarely observed. Outgrowth of resistant clones within progressed tumors appears to be inevitable. Recent immunologicaland clinical observations suggest that in background of this resistance the tumor-.induced disturbance of immunoregulation at least in part may play a role. Namely,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 regulatedimmune effectors. Consequently, the combination of MAPK cascade signaling pathway inhibitors and the immune effectors activating immunomodulators may bea promising new strategy.

Material and methods:

In a now 59 years old patient with inoperable (BRAF-mutant) low differentiated adenocarcinoma of bilary ducts after 30GY radiotherapyand two cycles (Gemcitabin+ Cisplatin) chemotherapy a rapid progression of lung, liver and brain metastases were by CT and MR established. Thereafter, a teatmentwith BRAF+MEK inhibitors (2x150 mg dabrafenib and 1 x 2 mg trametinib) was started. These inhibitors were combined with daily 45 mg/kg rice bran arabinoxylanconcentrate (using Biobran/MGN-3) (also known as Lentin Plus 1000)  which was shown to be a pathogenic associated molecular pattern (PAMP)-like molecule and can stimulate the type-1 innateimmune cells against tumor cells.

Results:

After the chemotherapy and prior to the start of second line treatment, the patient had a nearly terminal state of her rapidlyprogressive disease. Eight months after the combination of MEK / BRAF inhibitor and immunomodulator therapy nearly complete remissions of all metastases wasestablished 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 synergisticinhibit the tumor growth. Further clinical investigations are necessary to clarify this question.