Botox – an effective remedy for stomach cancer?

Botox, which is a botulinum toxin, has been inextricably connected with medicine for many years. It was first used in ophthalmology and neurology in early 1920s. Currently, it became an integral part of beauty parlors and salons. Scientists from Columbia University in New York and Norges Teknisk-Naturvitenskapelige Universitet in Trodheim in cooperation with researchers from Germany, Japan and Massachusetts Institute of Technology in Boston during their research on three mice models of stomach cancer have discovered that vagus nerves have a significant influence on the development of the cancer in its all stages and botulinum toxin, due to its properties, can block nerves thus contributing to increase of the chances to cure the disease.

Stomach cancer is currently the second, just after lung cancer, most frequent cancerous cause of death in patients all over the world. About a million of new cases are reported every year and about 800 000 people die because of it. Early stomach cancer usually does not show classic symptoms which would immediately indicate suspicion of cancerous process. First symptoms usually indicate other, less dangerous gastrological diseases such as, for example, gastritis, peptic ulcers or reflux what may cause the symptoms to be trivialized by the patient. Therefore, in 85-90% of the cases diagnosis is made in advanced stages what radically decreases chances for recovery and survival.

Currently, the standard treatment method for stomach cancer is a surgery during which doctors perform total or partial gastrectomy with removal of adjacent lymph nodes. Chemotherapy is usually used as a complementary treatment before or after the procedure or in combination with surgical palliative treatment in cases of unresectable stomach cancers. The main cause of low chemotherapy effectiveness is low sensitivity of cancerous cells to cytostatic agents. So far, doctors mostly try multifactorial treatment including surgeries, induction chemotherapy – used before planned surgery, radiation therapy and immunotherapy which aim is to cause specific or non-specific response of immunological system to the cancer. Effectiveness of those methods in most of cases is too low what is connected with high percentage of death rate among this group of cancer patients. Therefore, there are numerous ongoing clinical research which aim is to develop more effective schema of treatment increasing chances for survival.

International team of scientists from USA, Germany and Japan conducted numerous research which unambiguously confirm considerable role of the nervous system, especially of vagus nerve, on the process of cancer development. It turned out that microenvironment of cancerous tumors is characterized by especially abundant network of nerve connections. The number of these connections seems to correlate with stage of the cancer and its prognosis. Vagus nerve, which is the longest of cranial nerves, while going through opening of oesophagus to the abdomen has two trunks: left and right. Then it branches into numerous gastric plexuses respectively: right on the back side, left on the front side of the stomach. Acetylcholine secreted from endings of the vagus nerve influence muscarinic acetylcholine receptors of M3 type located in the area of cancer’s stem cells. Connection of receptor with a ligand causes increase in proliferation of cancer cells due to activation of wnt signaling pathway. It is also an important factor not only in development of metastases to such organs as: the liver, pancreas, transverse colon or diaphragm pillar, but also recurrence of the disease.

Experimental research conducted on mice have proved that denervation of parasympathetic part of the stomach significantly inhibits cancerous process, however, beneficial influence is observed only in denervated part. Two models were used in the experiment: surgical incision of the vagus nerve(both, bilateral and unilateral) and pharmacological method – topical injection of botulinum toxin of A type (botox) into mice with stomach cancer. Results of the research were surprising since it was proved that denervation of the stomach significantly strengthened anti-cancer activity of chemotherapy, simultaneously botox blocks muscarinic acetylcholine receptor thus inhibiting development of stomach tumours and metastases. It significantly contributes to elongation of mice’s life. It was estimated that botox injections during chemotherapy may increase the number of complete recoveries even by 35% because of higher sensitivity of denervated cancer cells to cytostatic agents. Soon, the second stage of clinical trials will be conducted in Norway and it will involve patients with non-operative stomach cancer.

Denervation method with the use of botulinum toxin seems to be extremely innovative and significantly less invasive solution than standard methods of treatment. Botox may be injected during gastroscopy what results in lower risk of complications and, what is extremely relevant for the patients, short hospital stay. What is more, botulinum toxin is injected topically what significantly limits the range of side effects in comparison with surgical denervation. Therefore, botox seems to be a new panacea, especially among a group of patients with non-operative stomach cancer or in patients in whom chemotherapy is impossible because of high toxicity.

So far used methods of stomach cancer treatment such as chemotherapy or radiotherapy have extremely destructive influence on human organism. First of all, they lead to reduction of immunological system effectiveness, myelosuppression, anemia, neutropenia, thrombocytopenia and to significant weakening of the body. The use of botulinum toxin as a new method of stomach cancer treatment seems to be not only cheaper, but also safer solution for the patient’s organism which is very ravaged because of developing cancerous process. The discovery brings new light on the future of oncology and botulinum toxin already seems to be a milestone in treatment of stomach cancer – cancer which currently gathers the most fatal harvest.

Written by: Joanna Szydełko, Magdalena Szydełko

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