China
Africa
Explore chapters and articles related to this topic
Immunotherapy in Head and Neck Cancers
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
apoptosis occurs when cells attempt to divide with damaged DNA. The cell is unable to complete mitosis and dies, in a process known as mitotic catastrophe. The majority of HNSCC lack normal p53-mediated G1/S checkpoint and are dependent on S and G2/M arrest to allow repair of DNA damage after irradiation. Hence, G2/M checkpoint control is a particularly appealing target for cancer-specific radiosensitisation.
Cell death after irradiation: How, when and why cells die
Published in Michael C. Joiner, Albert J. van der Kogel, Basic Clinical Radiobiology, 2018
Mitotic catastrophe is a term that has evolved to encompass the type of cell death that results from, or following, aberrant mitosis. This is morphologically associated with the accumulation of multinucleated, giant cells containing uncondensed chromosomes and with the presence of chromosome aberrations and micronuclei. This process occurs when cells proceed through mitosis in an inappropriate manner due to entry of cells into mitosis with unrepaired or mis-repaired DNA damage. This is frequently the case in cells following irradiation, which often display a host of different types of chromosome aberrations when they enter mitosis. Death, as defined here by the loss of replicative potential, can occur simply from a physical inability to replicate and separate the genetic material correctly, or to the loss of genetic material associated with this process. This is determined in large part by the types of chromosome aberrations that may be present in irradiated cells.
Basics of Radiation and Radiotherapy
Published in Prakash Srinivasan Timiri Shanmugam, Understanding Cancer Therapies, 2018
Prakash Srinivasan Timiri Shanmugam, Pramila Bakthavachalam
For the majority of cells, mitotic catastrophe-induced necrosis accounts for most of the cell death following ionizing radiation. Mitotic catastrophe is characterized by abnormal nuclear morphology (e.g., multiple micronuclei or multinucleated giant cells) following premature entry into mitosis by cells manifesting unrepaired DNA breaks and lethal chromosomal aberrations, this often resulting in the generation of nonclonogenic aneuploid and polyploid cell progeny. It is suggested that the abrogation of the G2-M checkpoint is due to overaccumulation of cyclin B and premature activation of the CDK1-cyclin B complex. Radiation-induced mitotic catastrophe is the predominant mode of cell death in P53-deficient tumor cells, which are defective in the G1-S checkpoint and can be selectively arrested by the G2-checkpoint upon DNA damage.
Expanding roles of cell cycle checkpoint inhibitors in radiation oncology
Published in International Journal of Radiation Biology, 2023
Sissel Hauge, Adrian Eek Mariampillai, Gro Elise Rødland, Lilli T. E. Bay, Helga B. Landsverk, Randi G. Syljuåsen
As described above, inhibition of WEE1, CHK1 or ATR can abrogate the S and G2 checkpoints after irradiation. Such checkpoint abrogation combined with induction of DNA damage by chemotherapeutic drugs or radiation, has been hypothesized as a treatment strategy for cancers with a deficient G1 checkpoint (Figure 2) (Powell et al. 1995; Russell et al. 1995). In this scenario, affected normal cells will still be able to arrest at the p53-dependent G1 checkpoint, repair the DNA damage and survive. Conversely, cancer cells that lack the G1 checkpoint will not be able to arrest the cell cycle and will be forced to progress through mitosis with unrepaired damage, ultimately causing loss of genetic material and cell death. This is termed mitotic catastrophe or mitosis-linked cell death (Eriksson and Stigbrand 2010). As many cancers have G1 checkpoint deficiency due to TP53 mutations, this treatment strategy may potentially confer tumor selectivity in a large number of patients (Tenzer and Pruschy 2003; Choudhury et al. 2006; Curtin 2012).
Insight into the evolutionary profile of radio-resistance among insects having intrinsically evolved defence against radiation toxicity
Published in International Journal of Radiation Biology, 2022
Jagdish Gopal Paithankar, Tanhaji Sandu Ghodke, Rajashekhar K. Patil
In living organisms, apart from direct and indirect modes of IR-induced toxicities, several other factors need emphasis. These factors decide the fate of an organism following induction of radiation toxicities. Subsequent to the IR exposure, cell activates pro-survival genes and promote DNA damage repair pathways, however, if the damage is irreparable cell activates either of the cell death pathway; mitotic catastrophe, apoptosis, necrosis autophagy, and senescence (Figure 1) (Eriksson and Stigbrand 2010; Sia et al. 2020). Onset of the apoptotic pathway is influenced by several factors including type of IR, dose of IR, exposure time, cell type, cell cycle phase, DNA damage repair capacity and p53 status (Casarett 1968; Eriksson and Stigbrand 2010). Subsequent to radiation exposure, depending on the extent of damage cell facets are decided. Mitotic catastrophe starts in cells that are unable of further replication following IR exposure. Activation of an apoptosis is dependent on the balance between pro- and anti-apoptotic factors. Necrotic pathway reported to be activated by cellular micro-environment, pH, ionic imbalance and energy loss following radiation exposure. Excessive autophagic responses were reported to activate an autophagic cell death pathway. The autophagy-related genes are activated following irradiation and they subsequently activate the autophagy pathway (Sia et al. 2020).
PARP inhibitors: clinical relevance and the role of multidisciplinary cancer teams on drug safety
Published in Expert Opinion on Drug Safety, 2022
Mafalda Jesus, Manuel Morgado, Ana Paula Duarte
In the literature, the precise mechanism of PARPi has not been described in an entirely clear manner, particularly in the way these inhibitors kill tumor cells. Several theories have emerged. Rose et al. reviewed different mechanisms of action by which PARPi induce their anti-cancer activity. However, it is unclear whether one or several of these mechanisms mediate the activity of PARPi [33]. This review describes two methods of cytotoxicity induced by PARPi. After some studies have shown that PAR recruits DNA repair proteins to the injury site, the first method relies on inhibiting the PARP enzyme. The inhibition of its catalytic activity occurs through interaction of PARPi with the binding site of the PARP enzyme cofactor, β-NAD+, in its catalytic domain. In this way, it becomes possible to prevent DNA repair, and consequently, by increasing repair errors, cell death of cancer cells is induced. The second method involves the ‘PARP trapping’ concept. In this case, the prevention of autoPARylation and the release of PARP1/PARP2 from damaged DNA by the inhibitors mediates its cytotoxic activity, preventing the recruitment of additional DNA repair proteins [26,34,35]. As an effect, the cell is unable to properly repair its DNA during replication, which can lead to mitotic catastrophe and subsequent cell death [36].