The role of a new <i>ALK</i> isoform in the diagnosis and targeted therapy of skin melanoma

Abstract

Contemporary discoveries of fundamental science in recent decades in the field of oncology have led to the emergence of new highly effective anticancer drugs: targeted drugs and immune checkpoint inhibitors, use of which has made a breakthrough in the treatment of oncological diseases, including skin melanoma. Melanoma is still one of the most cancerous tumors. The number of patients resistant to targeted therapy and immunotherapy increases in the world every year. Oncologists have practically no leverage to influence the disease after the development of resistance to this type of therapy. In this regard, scientists around the world are looking for new application points for targeted drugs. Nowadays, the most common treatment method is BRAF inhibitors, since the BRAF mutation is detected in 40–60 % of patients with skin melanoma. However, the resistance to BRAF inhibitor therapy occur in half cases after 6–8 months. To overcome the resistance to the target therapy is one the most important issue, the studying of new isoform of anaplastic lymphoma kinase (ALK) may help to solve this problem.Purpose of the study – to order the data of the leading researchers of a new isoform of ALK, and reveal the most promising directions for its further progress.In the article, there are comparisons and analyses the 6 of the largest studies over the past 5 years devoted to a new isoform of ALK.The joint inhibition of the new ALK isoform and BRAFV600 showed positive results in several studies with different levels of ALKATI expression (alternative initiation of ALK transcription). The new ALK isoform can stimulate oncogenesis only within a certain “threshold” level of expression. Immunohistochemical examination cannot be the main method for determining the expression of a new ALK isoform due to low sensitivity. In almost all studies, tumors with ALK translocation responded to therapy with ALK inhibitors.Even though that the role of the new ALK isoform has been studied in recent years, the optimal method for evaluating the expression of ALKATI in routine practice has not yet been determined. Additional studies are also needed to understand the effectiveness of the use of ALК inhibitors in combination with BRAF and ERK inhibitors. Of interest is the blockade of extracellular vesicles and the study of the role of interleukin-3 in the inhibition of ALKATI.