Although the role of senescence in many physiological and pathological processes is becoming more identifiable, many aspects of senescence are still enigmatic. A special attention is paid to the role of this phenomenon in tumor development and therapy. This review mainly deals with a large spectrum of oncological issues, beginning with therapy-induced senescence and ending with oncogene-induced senescence. Moreover, the role of senescence in experimental approaches, such as primary cancer cell culture or reprogramming into stem cells, is also beginning to receive further consideration. Additional focus is made on senescence resulting from mitotic catastrophe processes triggered by events occurring during mitosis and jeopardizing chromosomal stability. It has to be also realized that based on recent findings, the basics of senescent cell property interpretation, such as irreversibility of proliferation blockade, can be undermined. It shows that the definition of senescence probably requires updating. Finally, the role of senescence is lately more understandable in the immune system, especially since senescence can diminish the effectiveness of the chimeric antigen receptor T-cell (CAR-T) therapy. In this review, we summarize the current knowledge regarding all these issues.

Background: The biological role of EGFRvIII (epidermal growth factor receptor variant three) remains unclear. Methods: Three glioblastoma DK-MG sublines were tested with EGF (epidermal growth factor) and TGFβ (transforming growth factor β). Sublines were characterized by an increased percentage of EGFRvIII-positive cells and doubling time (DK-MGlow to DK-MGextra-high), number of amplicons, and EGFRvIII mRNA expression. The influence of the growth factors on primary EGFRvIII positive glioblastomas was assessed. Results: The overexpression of exoEGFRvIII in DK-MGhigh did not convert them into DK-MGextra-high, and this overexpression did not change DK-MGlow to DK-MGhigh; however, the overexpression of RASG12V increased the proliferation of DK-MGlow. Moreover, the highest EGFRvIII phosphorylation in DK-MGextra-high did not cause relevant AKT (known as protein kinase B) and ERK (extracellular signal-regulated kinase) activation. Further analyses indicate that TGFβ is able to induce apoptosis of DK-MGhigh cells. This subline was able to convert to DK-MGextra-high, which appeared resistant to this proapoptotic effect. EGF acted as a pro-survival factor and stimulated proliferation; however, simultaneous senescence induction in DK-MGextra-high cells was ambiguous. Primary EGFRvIII positive (and SOX2 (SRY-Box Transcription Factor 2) positive or SOX2 negative) glioblastoma cells differentially responded to EGF and TGFβ. Conclusions: The roles of TGFβ and EGF in the EGFRvIII context remain unclear. EGFRvIII appears as a weak oncogene and not a marker of GSC (glioma stem cells). Hence, it may not be a proper target for CAR-T (chimeric antigen receptor T cells).