Anti-Cancer Drugs - Essay Example

The tumor or cancer cells undergo the same cell cycle and consist of similar cell populations of proliferating, non-proliferating, and resting cells. Cell cycle phase-specific anticancer drugs are given for a particular phase and inhibit the further progression of the tumor cell (Ajithkumar et al 2011). The G1 phase-specific drugs inhibit the G1 phase of the tumor cells and have therapeutic consequences associated with them.

Cyclin-dependent kinases play an important role in the progression of the G1 phase. During the G1 to S phase transition, the phosphorylation of the retinoblastoma susceptibility gene, Rb, regulated by D-type cyclins and CDKs 4 and 6 is a major factor causing the cell cycle progression. By inhibiting the CDK activity, the G1 phase activity can be inhibited as well. First-generation CDK inhibitors include flavopiridol, UCN-01, and L86 8276, a non-chlorinated chemical form of flavopiridol. Flavopiridol causes G1 inhibition by its inhibitory action on CDK 2 and CDK4. UCN-01 and flavopiridol cell cycle repression are followed by apoptosis of the tumor cells and they have a cytotoxic effect. However, tumor cell selectivity is a major issue in their therapeutic affectivity. Non-tumor cells can also be affected by these anticancer drugs leading to apoptosis hence, non-tumor cells are also sensitive to CDK-inhibiting action (Shapiro & Harper 1999).

The limited inhibition activity caused by first-generation led to the formulation of purvalanol B a second-generation CDK inhibitor. This drug targets the ATP-binding sites and has shown higher selectivity for the CDKs. The activity of CDK4 and CDK 2 is inhibited 100-fold more selectively causing the inactivation of the Rb gene and ultimately cell arrest at the G1 phase (Shapiro & Harper 1999).  Corticosteroids and natural products like asparagine are also specific for cell arrest at the G1 phase of the tumor cells. Corticosteroids are effective in lymphoid-derived tumors while asparagines are effective in depriving the tumor cells of amino acids that are crucial for their proliferation and progression (Ajithkumar et al 2011).

New techniques and strategies are being employed to affect the normal cells as less as possible and selectively target the tumor cells only. The small-Molecule prodrugs technique is based on the selective activation of these prodrugs specifically in the tumor cells. This can be achieved by selective enzyme-regulated activation that is over-expressed in the tumor cells for instance capecitabine, a prodrug is bioactivated in the tumor cells by the enzymes carboxyl esterase and thymidine phosphorylase. Some prodrugs like OFU001 and Co (3) complexes can be activated by ionizing radiations in the tumor-specific areas. Another new strategy used to target tumor cells specifically in metastatic breast disease is Nanoparticle albumin-bound technology. In this technology nanoparticle that comprises taxane which is bound to the serum albumin is transported to the tumors. The drug is transported to the tumor cells through a pathway that is originally used by the tumor cells to transport nutrients through the gp60 pathway (Avendaño & Menéndez 2008).

     The low tumor selectivity of the G1-inhibiting drugs is a major shortcoming in their medicinal outcomes. The advancements in specific anticancer drug targeting have led to fewer cytotoxic reactions in the non-transformed cells. Many cancers are now treated with effective chemotherapeutic agents that are highly specific and also selective leading to an effectual therapeutic outcome.