Can a standardized plant immunomodulator (rice bran arabinoxylan concentrate/MGN-3) increase the effects of MEK and BRAF inhibitors with clinical benefit? Case report of a patient with carcinoma in biliary duct

  • Tibor Hajto
  • (edited by Chris Gutch PhD.)
  • 2017

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. Outgrowth of resistant clones within progressed tumors appears to be inevitable. Recent immunological

and 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 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 bilary 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. Thereafter, a teatment

with 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 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 prior to 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 was

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 synergistic

inhibit the tumor growth. Further clinical investigations are necessary to clarify this question.

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