**1. Introduction**

[40] Seo J.-O, Han S. I, Lim S.-C. Role of CDK8 and β–catenin in colorectal adenocarcino‐

[41] Morris E. J, Ji J. Y, Yang F, Di Stefano L, Herr A, Moon N. S, Kwon E. J, Haigis K. M, Naar A. M, Dyson N. J. E2F1 represses beta-catenin transcription and is antagonized

[42] Gurley K. E, Kemp C. J. Synthetic lethality between mutation in Atm and DNA-

[43] Curtin N. J, DNA repair dysregulation from cancer driver to therapeutic target. Na‐

PK(cs) during murine embryogenesis. Current Biology 2001; 11: 191-194.

ma. Oncology Reports 2010; 24: 285-291.

32 Updates on Cancer Treatment

ture Reviews Cancer 2012; 12: 801-817.

by both pRB and CDK8. Nature 2008; 455, 552-556.

Advanced cancer is a malignant disease that has spread to other places in the body and usually cannot be cured or controlled with treatment. The treatment and care of advanced cancer patients is focused on the management and relief of symptoms, improving the patient's comfort and quality of life. Such patients are given symptomatic treatment. At the same time the status of anti-tumour immunity is a key link in the carcinogenesis chain of advanced cancer. This means that anti-tumour immunity could be considered as a target for pathogenically justified immunotherapy. It is also known that the activity of anti-tumour immunity deter‐ mines the survival of patients with cancer. It should be mentioned that an active development of immunotherapy had promised drastic changes in the management of cancer, as well as an increase in survival of patients living with cancer. However, that expectation has not yet been fulfilled. Clinical studies show that an initially compromised anti-tumour immunity of patients living with cancer cannot be surely recovered by means of immunotherapy. At the same time the use of immunotherapy in some cancer patients could be dangerous as well as useless due to the possibility of the stimulation of cancer development, for example through the induction of Treg cells [1]. At first sight an idea to administer pathogenically justified immunotherapy to patients with advanced cancer seems in appropriate. However, it could be accepted if applied with immunotherapy for advanced cancer patients based on deterministic positions of cellular/molecular and/or genetic levels.

The systemic view in the whole body approach to treatment suggests mandatory consideration of the state of higher nervous activity (mental state), which provides a serious influence on the development and outcome of cancer disease. For instance, 'depression is worsening the potentially short lives of patients living with cancer' [2]. In this regard we assumed that some patients with advanced cancer suffer from psychogenically determined immunosuppression as an outcome of untreated psychoemotional disorders that have occurred before a diagnosis of cancer. In fact, those patients went through massive psychotraumatic events that accumu‐

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lated through the massive stress connected with a first diagnosis of cancer. We also assumed that the immunotherapy of advanced cancer patients with a psychogenic medical history should be preceded with an effective correction of psychoemotional disorders in order to avoid a psychogenic immunosuppressive influence. The objective of this work is the development and implementation of a psychoimmunological approach to the treatment of advanced cancer patients with a psychogenic medical history.

#### **1.1. Theoretical justification for a psychoimmunological approach to the treatment of advanced cancer patients with a psychogenic medical history**

Today there is no doubt that immune dysfunctions are the backbone of tumour pathogenesis. This immune dysfunction, along with destruction of the cellular genetic apparatus in the malignant cells, occurs in the form of the cell component of the immune system dysfunction along with the malfunction of cell control and cell differentiation mechanisms, immune tolerance, and inability to provide an effective immune response to a developing tumour [3, 4]. In this connection it was logical to use the wide range of immunotherapy methods in modern oncology. Despite being a new step in malignant tumour treatment it has not solved the problem of its effective treatment [5, 6].

At the same time, laboratory and clinical trials have shown linked and multi-functional interconnections between the two most important integrative systems of the human organism, which are the immune and the nervous systems [7-9], which formed the basis of the develop‐ ment of modern scientific trends of the psychoneuroimmunology and psychoimmunology of cancer [10]. The conclusions of the scientific research on the influence of chronic psychoemo‐ tional stress (CPES) to an organism of healthy and unhealthy individuals, including those with cancer, are most interesting from the practical point of view. Nowadays the somatic outcomes of CPES are well known: the CPES is able to damage the cell's DNA and inhibit DNA repair through the activation of endogenous mutagens, which are the reactive species of oxygen, nitrogen, etc. This leads to genome instability [11, 12]. CPES is always followed by immuno‐ suppression, a decrease in the quantity and cytotoxic activity of CD8+ and NK-cells, and dysfunction of their supervising functions, processes of apoptosis, activation of proinflamma‐ tory cytokines and sustentation of the non-cropped areas of chronic inflammation [13-15]. All of these lead to a concentration of malignant cells in the body with an increase in their invasive potentiality [16]. CPES is linked with a high risk of development, progress and recurrence of malignant tumours, and the high mortality rate of cancer patients [17, 18]. The CPES also leads to hippocampal neuronal degeneration as well as amygdala atrophy [19], prolonged hyper‐ activity of the hypothalamo-pituitary-adrenocortical axis [20], and accelerated aging of the human body [21]. Therefore, the extensive and deep somatic damaging effect of CPES suggests a significant role of psychogenic factors in the development, recurrence and progression of cancer disease in some cancer patients with a psychogenic medical history. On the basis of the above, it is logical to assume that it is difficult to eliminate the factors compromising the immune system due to psychogenic influence and the suppression of anti-tumour immunity without effective elimination of persistent tonic descending influences of the central nervous system and the higher nervous activity to the body of cancer patients with a psychogenic medical history. The confirmation of the dependency of anti-tumour immune activity to higher nervous activity is presented by therecently discovered phenomenon of the spontaneous increase in anti-tumour activity of the immune system after the effective relief of psychoemo‐ tional disorders in cancer patients with a psychogenic medical history [22].

Thereby, advanced cancer patients with a psychogenic medical history require a special pathogenesis-based psychoimmunological cancer treatment in order to restore their mental condition, increase their quality of life, activate an anti-tumour immunity and to block the progression of cancer. The main content of psychoimmunological cancer treatment consists of compliance with a strict sequence of two stages of cancer treatment: psycho-correction and immunoactivation. The main objective of the first stage of cancer treatment (psycho-correc‐ tion) is an effective and sustainable elimination of CPES effects that appear in different psychoemotional disorders such as anxiety, depression, etc. The main objective of the second stage of cancer treatment (stage of immunoactivation) is the activation of specific anti-tumour immunity.
