Chemotherapy cell-cycle specificity

The extracellular domain of the HER-2 neu molecule is the therapeutic target for the specific IgGlx humanized chimeric monoclonal antibody Trastuzumab (Herceptin ), approved 1998 and found to be effective in malignancies with HER-2 overexpression. An important aspect of this specific immunotherapy includes the efficiency against non-proliferating disseminated tumor cells (dormant cells), which are usually in the GO phase of the cell cycle, where conventional chemotherapy is less effective. The HER-2 neu molecule is also the target for specific tyrosine kinase inhibitors such as Tykerb (lapatinib ditosylate), which block the kinase-substrate interaction and the extracellular tyrosine kinase receptors on tumor cells. 

Many cancer therapies use non-S-phase-specific cytotoxic agents and the question arises whether a cell-cycle inhibitor like rhMIP-la/BB-10010 can protect normal cell from these agents. This question has been addressed using the clinically relevant non-S-phase-specific cytotoxic drug cyclophosphamide in murine chemotherapy models, which are typically less myeloablative than those described above (38). In these studies BB-10010 was administered continuously by osmotic minipump during days 0-7 at 40 pg... 

Once inside the host cell, the vims must replicate its own nucleic acid. To do this, it often uses part of the normal synthesizing machinery of the host cell. If the vims is to continue its growth cycle, viral nucleic acid and viral protein must be propedy transported within the cell, assembled into the infective vims particle, and ultimately released from the cell. All of these fundamental processes involve an intimate utilization of both cellular and viral enzymes. Certain enzymes that are involved in this process are specifically supplied by the invading vims. It is this type of specificity that can provide the best basis for antiviral chemotherapy. Thus an effective antiviral agent should specifically inhibit the viral-encoded or virus-induced enzymes without inhibition of the normal enzymes involved in the biochemical process of the host cell. Virus-associated enzymes have been reviewed (2,3) (Table 1). 

It is interesting to note that the central focus of study of conventional (cytotoxic) chemotherapy — indeed, all medicinal regimens — is the same as that of alternative and complementary medicine. The snbject in both cases is, in general, that of biochemistry, or call it the biochemical revolntion. That is, both are ultimately concerned with cell metabohsm and its various biochemical pathways and/or cycles for growth, maintenance, and modulation or immolation — which are embedded with, or controlled by, the proteinaceous biocatalysts called enzymes. In turn, the action of these enzymes — each specific to a particular biochemical reaction — is modulated or blocked (and rarely promoted) by a class of organic and inorganic substances broadly known as enzyme inhibitors. 

---