ANTONIN BUKOVSKY, MD, Ph.D. an Obstetrics and Gynaecology specialist along with collaborator wrote and published “Former Effective Immunotherapy without adverse events of Inoperable Epithelial Ovarian Cancers and a Prospect for the Immune Prophylaxis” on recent cancer treatments by immune checkpoint blockades which are restricted because of serious antagonistic occasions brought about by modification of the immune system required for homeostasis of normal tissues. Basic cancer chemotherapy and multivisceral cytoreductive surgery also markedly alter the quality of patients’ lives.
Research has shown that immune-related adverse occurrences ranged from mild to lethal. It was seen that these were found to accompany immunotherapy with checkpoint inhibitors, however, the underlying causes were still unknown. Review of 22 clinical trials (1265 cases) found that the overall incidence of adverse events was 72% and it resulted in the death of 0.86% (11 cases) of the checkpoint blockade treated patients. Inflammation of gastrointestinal tract, skin lesions (rash, pruritu, and vitiligo), hepatitis, thyroiditis, uveitis, sarcoidosis, Guillain-Barre syndrome, immune-mediated cytopenia, and polymyalgia were some adverse events. The adverse events also have the potential to alter the quality of life, which can be caused by common cancer chemotherapy-nausea, vomiting, constipation, hair loss, etc.
According to the National Cancer Institute, immunotherapy is a type of cancer treatment that helps an individual’s immune system to fight cancer. An immune system aids the body in fighting infections and other diseases. It is primarily made up of mononuclear white blood cells and organs and tissues present in the lymphoid system. Cancer immunotherapy is a kind of biological therapy i.e., it is a treatment, which uses substances stimulating immune system reactivity against the cancer cells.
A prime reason why cancer cells that are expressing allogeneic antigens can thrive is because of their ability to hide from the immune system by utilizing the mammalian ability to support allogeneic embryo implantation and fetal growth. However, with the use of some immunotherapies, it becomes easy to identify cancer cells. This further assists the immune system to find and destroy them. Certain other immunotherapies also boost the immune system to work better against cancer.
On examining the data, it was found that the survival of women with epithelial ovarian cancers (EOCs) has remained unsatisfactory for the last several decades. It was also that present cancer treatments by immune checkpoint blockades were limited. The common cancer chemotherapy with platinum-based treatment eventually led to neurotoxicity with chronic debilitation. The survival rate of patients suffering from EOCs was low. It showed poor improvement despite high dose chemotherapy, extensive cytoreductive surgery, checkpoint blockades, etc. All this triggered Bukovsky to question and study this particular aspect of cancer.
He realized that novel therapies without adverse events and prevention of cancer relapses were needed to improve treatment and long-lasting survival of patients with EOCs. Bukovsky has tried to explain effective cancer immunotherapy without adverse events. For this, he has felt the need to comprehend detailed information of the immune system niche involvement in the homeostasis of all body normal tissues and the host immune niche support of cancer growth in vivo.
Former elimination of the host antibodies blocking T cell effectors by intermittent doses of cyclophosphamide that is exhibiting significant immunomodulatory anticancer effects, facilitation of the immune system reactivity against alloantigens of cancer cells by blood transfusions, and augmentation of anticancer immunity by bacterial toxins, resulted during the subsequent treatment-free period into rejection of advanced inoperable EOCs without any adverse events during the treatment. To help prevent cancer relapses, patients treated for advanced primary epithelial cancers should be considered as candidates for continuously stimulating immune anticancer reactivity by treatments altering cancer stem cells, such as daily metformin and weekly raw shiitake mushroom containing anticancer substance lentinan consumptions.
The reported immunotherapy was accompanied by regeneration of the metastatically altered tissues into healthy conditions, including complete regeneration of the liver and other tissues in abdominal cavity affected by severe EOC metastases, without a need of cytoreductivemulti-visceral surgery, such as intestinal resection, diaphragm stripping or resection, splenectomy and liver resection, which can have severe consequences.
In addition to the above, Bukovsky’s study provides a solution to treat severe immune-related adverse events after checkpoint blockades. His research addresses the question of why epithelial cancer cells grow in immunocompetent mammalian organisms and the exact host support of EOC growth.
An otherwise untreated rectal cancer resolved after a severe toxic dermatitis lasting over one week, which was caused by accidental consumption of an uncooked larger raw shiitake mushroom.
After an in-depth study and analyses of the case studies, Bukovsky understood that long-term survival depends on effective prevention of cancer relapses. A study revealed that oral metformin is that medicine which decreases the risk of cancer and also improves cancer survival. Another study revealed the effective consumption of raw shiitake mushrooms. It was found that daily 2g metformin and weekly consumption of a single larger raw shiitake mushroom in salads prevented malignant recurrences over the next 25 years, with no subsequent signs of dermatitis.
Hence, Bukovsky concluded that the available data exhibited the current cancer immunotherapy by immune checkpoint blockades might lead to a high-grade multiorgan alteration and patients’ death. Subsequently, it was observed that alteration of the natural immune system’s role in tissue homeostasis might be the cause of immune adverse events. Higher doses of chemotherapy during cancer treatment could be the cause of adverse events as well. This eventually led to a deterioration in the quality of the patient’s lives. Therefore, Bukovsky proposed effective immunotherapy of inoperable EOCs without adverse events, based on his former treatments of EOCs. He suggested that the aforementioned can be facilitated by consumption of substances stimulating immune reactivity against cancer stem cells, for example, daily metformin along with weekly raw shiitake mushroom containing lentinan, which was reported to stimulate immune system reactivity against cancer stem cell, could accelerate cancer regression and prevent for long term cancer relapse. However, a caveat provided at the end of the study mentions that carefully designed modern clinical trials on patients with advanced epithelial malignancies are needed to investigate the potential of the mentioned therapies.
Bukovsky’s research study comes at a time when the cases for EOCs are on the rise globally. This groundbreaking study can be of great use to the medical community trying to find solutions for this unresolved medical condition.
For details and figures see the free published article at:
About Antonin Bukovsky:
Antonin Bukovsky (firstname.lastname@example.org, email@example.com) was born in the Czech Republic, graduated as M.D. in 1969. Beside/GYN clinical work, he concentrated on the ovarian and cancer research. In 1990, he was invited to the Methodist Hospital in Indianapolis, IN, to study male reproduction. In the fall of 1991, he joined UT-GSM in Knoxville, TN to return toward ovarian and cancer research, and became UT Professor in 2002 and US citizen in 2005. He has published over 130 scientific articles. In 2011, he with the Institute of Biotechnology Czech Academy of Sciences, Czech Republic.