Carcinogenic potential of antitumor therapies - is the risk predictable?

The growing number of successfully cured cancer patients has created a new field in oncogenesis. The life expectancy of such patients has increased, however this favorable event may create enough time for epigenetic events to occur which can cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are second primary malignancies as well as therapy-related neoplasms in case the treatment of the first neoplasm is a direct cause. Second primary malignancies can be hematological neoplasms or solid tumors, with solid tumors having higher frequency. Hematological malignancies, especially t MDS (therapy-related myelodysplastic syndrome) and t AML (therapy-related acute myeloid leukemia), are causally associated with cytotoxic chemotherapy, while secondary solid tumors are related to radiotherapy. The pathogenic mechanisms of clonal selection in second malignancies are in connection with induction of fusion oncogenes, induction of genetic instability, selection of resistant cell clones and hereditary predisposition. The most common oncogenic agents are external (antineoplastic systemic treatments including radiation therapy), patient-specific factors (genetic, demographic, hormonal) and tumorspecific factors (tissue radiosensitivity, immunodeficiency). There are special features in the clinical picture, biological characteristics and evolution of the second neoplasm - different latency period, aggressive course and treatment resistance. Risks, types and characteristics of secondary malignancies are analyzed in specific groups of patients. For example, the peak of t-AML is several years after a primary malignancy and for solid tumors, the risk increases progressively during the observation period. In this review, the authors outline that the risk of second malignancies is predictable and can be controllable by adequate monitoring of patients as well as by personalized treatment of the first neoplasm.