Senescent cells and SASP in cancer microenvironment: New approaches in cancer therapy

Abstract

Cellular senescence was first described as a state characterized by telomere shortening, resulting in limiting cell proliferation in aging. Apart from this type of senescence, which is called replicative senescence, other senescence types occur after exposure to different stress factors. One of these types of senescence induced after adjuvant therapy (chemotherapy and radiotherapy) is called therapy-induced senescence. The treatment with chemotherapeutics induces cellular senescence in normal and cancer cells in the tumor microenvironment. Thus therapy-induced senescence in the cancer microenvironment is accepted one of the drivers of tumor progression. Recent studies have revealed that senescence-associated secretory phenotype induction has roles in pathological processes such as inducing epithelial-mesenchymal transition and promoting tumor vascularization. Thus senolytic drugs that specifically kill senescent cells and senomorphic drugs that inhibit the secretory activity of senescent cells are seen as a new approach in cancer treatment. Developing and discovering new senotherapeutic agents targeting senescent cells is also gaining importance. In this review, we attempt to summarize the signaling pathways regarding the metabolism, cell morphology, and organelles of the senescent cell. Furthermore, we also reviewed the effects of SASP in the cancer microenvironment and the senotherapeutics that have the potential to be used as adjuvant therapy in cancer treatment.

Keywords: Cancer; SASP; Senescence; Senolytics; Senomorphics; Senotherapy.