New Approaches for Cancer Treatment: Antitumor Drugs Based on gene-Targeted Nucleic Acids

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Abstract

Currently, the main way to fight cancer is still chemotherapy. This method of treatment is at the height of its capacity, so, setting aside the need for further improvements in traditional treatments for neoplasia, it is vital to develop now approaches toward treating malignant tumors. This paper reviews innovational experimental approaches to treating malignant malformations based on the use of gene-targeted drugs, such as antisense oligonucleotides (asON), small interfering RN A (siRN A), ribozymes, and DNAzymes, which can all inhibit oncogene expression. The target genes for these drugs are thoroughly characterized, and the main results from pre-clinical and first-step clinical trials of these drugs are presented. It is shown that the gene-targeted oligonucleotides show considerable variations in their effect on tumor tissue, depending on the target gene in question. The effects range from slowing and stopping the proliferation of tumor cells to suppressing their invasive capabilities. Despite their similarity, not all the antisense drugs targeting the same region of the mRN A of the target-gene were equally effective. The result is determined by the combination of the drug type used and the region of the target-gene mRN A that it complements.

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At the current stage of modern medicine, one of the most important projects is to increase the effectiveness of cancer treatment by searching for and developing new therapies and improving traditional therapeutic approaches. A combination of surgery, radio- and chemotherapy is still the golden standard for cancer treatment, and these approaches have led to an 8-fold increase in patient survival over the last 30 years. The negative features of surgery-only treatment are recurrent tumors, the spread of metastases, and the formation of unresectable malignant malformations. This forces doctors to use radio- and chemotherapy. Alas, even this combination of powerful cancer therapies often doesn’t bring positive results. Therefore, despite the undeniable achievements of modern oncology, increasing the effectiveness of cancer treatment is of utmost importance. During the last several decades, complex chemotherapy has become the main approach for treating cancer patients. Its use however is limited, despite the fact that it increases survival rates by 30% to 90%, depending on the type of malformation. The main hindrances are systemic toxicity, nonselective action (the effect is not specifically targeted towards tumor tissue), and the emergence of drug-resistant tumor cell clones. Recent discoveries have provided scientists with detailed knowledge of the molecular processes underlying carcinogenesis, tumor invasiveness, angiogenesis, and metastasis, as well as other processes, such as tumor suppression, growth control, apoptosis, and immune response. These data have led to the development of a new generation of chemotherapeutic drugs, such as Gleevec (aka Glivec or Imatinib mesylate), Mabtherа (aka Rituximab), etc., which have a highly selective effect on their cellular target. It is well known that creating a new drug takes about 10–20 years of research, and improving its selectiveness increases its cost manifold. Currently, chemotherapy as a high-dose active attack aimed at tumor cells is at the limit of its ability.
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About the authors

O A Patutina

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Novosibirsk

N L Mironova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Novosibirsk

V V Vlassov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Novosibirsk

M A Zenkova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: marzen@niboch.nsc.ru
Novosibirsk

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