Prostate cancer is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related deaths in Western civilization. Although localized prostate cancer can be treated effectively in different ways, almost all patients progress to the incurable metastatic castration-resistant prostate cancer. Due to the significant mortality and morbidity rate associated with the progression of this disease, there is an urgent need for new and targeted treatments. In this review, we summarize the recent advances in research on identification of prostate tissue-specific antigens for targeted therapy, generation of highly specific and selective molecules targeting these antigens, availability of therapeutic radionuclides for widespread medical applications, and recent achievements in the development of new-generation small-molecule inhibitors and antibody-based strategies for targeted prostate cancer therapy with alpha-, beta-, and Auger electron-emitting radionuclides.

Coralyne is a synthetic analog of berberine related to protoberberine-isoquinoline alkaloids. Isoquinoline derivatives and analogs are renowned as potent radiosensitizers with potential medical application. In the present study, we investigated the effect of coralyne on the cell death, cytoskeletal changes and cell cycle progression of irradiated A549 cells. A clonogenic assay revealed that coralyne pretreatment decreased the viability of A549 cells in a time- and dose-dependent manner. Moreover, exposure to coralyne and ionizing radiation (IR) markedly altered the filamentous actin cytoskeletal architecture and integrin-β binding sites of A549 cells. Treatment with 1–25 µM coralyne in combination with 2 Gy of IR significantly reduced the percentage of cells in G2/M phase compared with 2 Gy IR alone. These results indicate that coralyne is a potent radiosensitizing agent that may find an application in medicine.

Gynaecologic cancers are common among women and treatment includes surgery, radiotherapy or chemotherapy, where the last two methods induce DNA damage in non-targeted cells like peripheral blood lymphocytes (PBL). Damaged normal cells can transform leading to second malignant neoplasms (SMN) but the level of risk and impact of risk modifiers is not well defined. We investigated how radiotherapy alone or in combination with chemotherapy induce DNA damage in PBL of cervix and endometrial cancer patients during therapy. Blood samples were collected from nine endometrial cancer patients (treatment with radiotherapy + chemotherapy—RC) and nine cervical cancer patients (treatment with radiotherapy alone—R) before radiotherapy, 3 weeks after onset of radiotherapy and at the end of radiotherapy. Half of each blood sample was irradiated ex vivo with 2 Gy of gamma radiation in order to check how therapy influenced the sensitivity of PBL to radiation. Analysed endpoints were micronucleus (MN) frequencies, apoptosis frequencies and cell proliferation index. The results were characterised by strong individual variation, especially the MN frequencies and proliferation index. On average, despite higher total dose and larger fields, therapy alone induced the same level of MN in PBL of RC patients as compared to R. This result was accompanied by a higher level of apoptosis and stronger inhibition of cell proliferation in RC patients. The ex vivo dose induced fewer MN, more apoptosis and more strongly inhibited proliferation of PBL of RC as compared to R patients. These results are interpreted as evidence for a sensitizing effect of chemotherapy on radiation cytotoxicity. The possible implications for the risk of second malignant neoplasms are discussed.

We studied the effects of Aeroxide P25 titanium dioxide nanoparticles (TiO₂ NPs) with a diameter of 21 nm on induction of DNA damage and long-term survival of three human cell lines: hepatocellular liver carcinoma HepG2, colorectal adenocarcinoma HT29 and lung carcinoma A549. The endpoints examined were DNA breakage estimated by the comet assay and oxidative base damage recognized by formamide-pyrimidine glycosylase (FPG) estimated with the FPG⁺ comet assay, frequencies of histone γH2AX foci and micronuclei, apoptosis, cell metabolic activity measured by mitochondrial activity (MTT) assay and long-term survival measured by colony-forming ability. Each cell line had a different pattern of DNA breakage and base damage vs. nanoparticle (NP) concentration and treatment time. There was no increase in the frequencies of histone γH2AX foci and micronuclei as compared to those in the untreated cells. In parallel with these results, no induction of apoptosis has been found in none of the cell lines tested. The reported experiments provided no evidence of the long-term in vitro toxicity of Aeroxide P25 TiO₂ NPs, despite a slight decrease in mitochondrial activity and cell survival during the first 72 h.

The DNA damage response (DDR) of cells to low dose and low dose rate ionizing radiation is weak and remains a matter of controversy. The response can be studied by exposing cells to a low adapting dose (AD) and, subsequently to a high challenging dose (CD), where the response is strong. The aim of the present investigation was to analyse the DDR in cells exposed to very low dose rate AD and a high dose rate CD, with special focus on the role of the ATM kinase. U2OS cells (with wild type p53) were exposed to gamma radiation AD of 5.9 mGy at 31 µGy/h and of 10.5 mGy at 55 µGy/h. ATM was inhibited by addition of KU-55933. Adapted cells were exposed to a CD of 1 Gy photon radiation at 1 Gy/min. The studied endpoints included kinetics of 53BP1 foci formation and decay, cell cycle progression and gene expression. In some experiments, ATM was inhibited by KU-55933. AD alone led to a significant increase in 53BP1 foci, even in the presence of KU-55933, and it modulated the response to CD. KU-55933 failed to inhibit the induction of foci by AD and AD+CD, while foci induction by CD alone was inhibited. KU-55933 potentiated the G2 block in AD+CD-exposed cells. Gene expression was modulated by AD. In conclusion, AD differentially modulated the response of cells when given alone and after the CD, in absence and presence of KU-55933.

Despite significant progress in the treatment of cancer patients, modern oncological therapy faces numerous challenges that are primarily related to the lack of response to treatment caused by the resistance of cancer cells to chemotherapeutics