Anti-Cancer Drugs

1. inhibition of virus absorption
2. inhibition of virus cell defusion
3. inhibition of HIV integrase
4. inhibition of viral DNA or RNA synthesis
- inhibitors of viral DNA polymerase
- inhibitors of the reverse transcription
- acyclic nucleoside phosphonate
5. viral protease inhibition
6. viral neuraminidase inhibition
7. inhibition of IMP dehydrogenase
8. inhibition of S-adenosylhomocysteine hyfrolase

In malignant cancer cells cancer cells break away from the primary tumor site, invade a blood or lymphatic vessel, to form metastasis site.

Usually, cells only stick to similar cells. The signature on the cell surface is transmitted via cell-adhesion moleculed (e.g. cadherins). Moreover, cells are connected to each other via mounting them on the ectracellular matrix (EM).

Adhesion to EM involves molecules called integrins.

The protein matrix metalloproteinase degrades the the extracellular matrix, and therefore is important for leaving the site of primary tumor and attaching to the secondary site.

If a non-cancer cell is detached from the extracelluar matrix it stops growing and apoptosis is triggered.

In the metastasized cells adhesion molecules are missing, so that they can leave the site of the primary tumor.

Cancer cells are often called immortal since these seems to be no limit for how often they can devide.

Life-time of normal limited to 50-60 cell devisions. This is regulated by telomeres. The telomeres are at 3′ end of chromosomes. After each replication about 50-100 base pairs are lost.

At some point telomeres become too short too be effective and the DNA becomes unstable thereby limiting the replication. Cancer cells posses an enzyme called telomerase which maintains the length of the telomeres and thereby allows more DNA replications.

• Necrosis is the uncontrolled cell death. In contrast with apoptosis, clean up of cell debris by pahgocytes of the immune system is generally more difficult. There are many cause of necrosis including injury, infection, cancer, infarction, toxins and inflammation. Necrosis can arise from lack of proper care to a wound site. Usually cell outlines do not stay intact, and cell debris is released into the environment.
• Apoptosis is the programmed cell death. It is used by organisms to control the number of cells and tissue size. The cells during apoptosis shrink, but uncontrolled release of cell debris into the environment occurs. The immune system usually “clean up” the dying cells and content is recycled.
  Apoptosis is triggered by an extracellular signal to the CD95 receptor. In response to that signal a set of cysteine proteases, called caspases are activated, that are largely responsible for the
  morphological changes observed.

• Progression through the cell cycle is controlled by cyclin-dependent kinase (CDKs)
• Binding of the cyclin with its associate kinase trggers to move the cell to another phase
• inhibitory proteins are present that can modify the effect of cyclins. These include p15 and p16, that block activity of the cyclin D-CDK complex. Another regulator is p21, that is controlled by the tumor suppressor protein p53.
• Over-active cyclins or CDKs have been associated with many tumors. Excessive production of cyclins or CDKs or insufficient production or in sufficient production of CDK inhibitors leads to disruption of the normal regulation of the cell cycle.

• G1 phase (gap1): Cell grows in size and prepares to copy its DNA in response to various growth factors.
• S phase (synthesis): Replication of DNA, copying of the chromosome.
• G2 phase (gap 2): Preparation for cell division. Check copied DNA and repair damaged copies.
• M phase (mitosis): Formation of the mitotic spindle, and separation into two individual cells (cell division).