• Stages of Ovarian Cancer

Stage I -indicates confinement to the ovary.

Stage II- tumors extend beyond the ovary to adjacent pelvic structures i.e fallopian tube or uterus.

Stage III -indicates metastasis to the peritoneum and/or regional lymph nodes.

Stage IV tumors have metastasized beyond the peritoneum to distant sites.

• Cell Cycle and Cancer:

Coordinated progression through the cell cycle is crucial for the maintenance of genome stability ⁽Stevens et al., 2003)^. This is particularly the case for the main tasks of the cell cycle: DNA replication and mitosis.

The decision to commit to cell division is controlled by a complex signalling system, the retinoblastoma protein (RB) pathway; that is, the major target of human cancer-causing mutations. ⁽Ohtsubo et.al., 1993⁾

                                                                                     Mechanisms have evolved to remove damaged molecules and make necessary repairs. These are called Cell Cycle Check points                

Cells are particularly susceptible to the harmful effects of DNA damage at two points in the cell cycle: S phase and M phase.

Cell-cycle progression is blocked at three points: before S-phase entry (the G₁ DNA damage checkpoint), during S phase (the intra-S phase DNA damage checkpoint), and before M-phase entry (the G₂ DNA damage checkpoint). (NCI)

Table 1 Cell-Cycle Genes Commonly Mutated or Altered in Expression in Human Cancer

Gene Protein Function Alteration in Cancer CCND1,2,3 D cyclins Positive regulator of CDK4/6 Overexpressed CCNE1 Cyclin E1 Positive regulator of CDK2 Overexpressed, deregulated CDKN2A p16, INK4aa CDK4/6 inhibitor Mutated, deleted, methylated CDKN1B p27Kip1 CDK2 inhibitor Underexpressed CDKN1C p57Kip2 CDK2 inhibitor Underexpressed, methylated SKP2 Skp2 Turnover of p27 Overexpressed CDK4 CDK4 Inactivates pRb p16-resistant mutations hCDC4 hCdc4 Turnover of cyclin E Mutated, deleted RB1 pRb Represses E2F transcription Mutated, deleted RB2 p130 Inhibits CDKs, represses E2F Mutated, deleted CKS1,2 cks1, cks2 CDK-binding proteins Overexpressed AURKA Aurora A Mitotic kinase Overexpressed PLK Plk1 Mitotic kinase Overexpressed PTTG1 Securin Anaphase inhibitor Overexpressed TP53 p53 Checkpoints, apoptosis Mutated, deleted MTBP MDM-2 Inhibitor of p53 Overexpressed CDKN2A p14Arf,a Activator of p53 Mutated, deleted ATM ATM Checkpoints, repair Mutated, deleted CHK2 chk2 Checkpoints Mutated NBS1 Nbs1 Checkpoints, repair Mutated (Cancer, principles and practice of onchology,8theditionDeVita)

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