Anticancer drugs

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Anticancer DrugsMansoura universityFaculty of pharmacyDept. of biochemistrySupervisor Prof. Dr. Laila EissaNada Mohammed Atta (806)Nada Ibrahim Zakaria (807) Nada Hassan Ramzy (808)Nada Saeed Abd Ellatif (809)Nada Tariq Ali (810)

Brief of Cancer Cancer starts when cells in a part of the body start to grow out of control. Cancer cell growth is different from normal cell growth. Instead of dying, cancer cells continue to grow and form new, abnormal cells. Cancer cells can also invade (grow into) other tissues, something that normal cells cant do. Growing out of control and invading other tissues are what makes a cell a cancer cell.

Brief of Cancer Cells become cancer cells because of DNA damage. DNA is in every cell and it directs all its actions. In a normal cell, when DNA is damaged the cell either repairs the damage or dies. In cancer cells, the damaged DNA is not repaired, but the cell doesnt die like it should. Instead, the cell goes on making new cells that the body doesnt need. These new cells all have the same damaged DNA as the first abnormal cell does.People can inherit abnormal DNA (its passed on from their parents), but most often DNA damage is caused by mistakes that happen while the normal cell is reproducing or by something in the environment. Sometimes the cause of the DNA damage may be something obvious likecigarette smokingorsun exposure. In most cases, the cancer cells form a tumor. Over time, the tumors can replace normal tissue, crowd it, or push it aside. Some cancers, likeleukemia, rarely form tumors.

"Drivers" of Cancer

The genetic changes that contribute to cancer tend to affect three main types of genes. proto-oncogenes,tumor suppressor genes and DNA repair genes. These changes are sometimes called drivers of cancer.Proto-oncogenes are involved in normal cell growth and division. However, when these genes are altered in certain ways or are more active than normal, they may become cancer-causing genes (or oncogenes), allowing cells to grow and survive when they should not.Tumor suppressor genes are also involved in controlling cell growth and division. Cells with certain alterations in tumor suppressor genes may divide in an uncontrolled manner.DNA repair genes are involved in fixing damaged DNA. Cells with mutations in these genes tend to develop additional mutations in other genes. Together, these mutations may cause the cells to become cancerous.

How cancer spreads?Cancer cells often travel to other parts of the body where they can grow and form new tumors. This happens when the cancer cells get into the bodys bloodstream or lymph vessels. The process of cancer spreading is calledmetastasis.

What are the different types of cancer treatment?

Surgery, chemotherapy, and radiation are the most common types of cancer treatment.Chemotherapy is the use of drugs to kill cancer cells. However, when most people use the word chemotherapy they are referring specifically to drug treatments for cancer that destroy cancer cells by stopping their ability to grow and divide.Surgery is often the first treatment option if the tumor can be taken out of the body. Sometimes only part of the tumor can be removed. Radiation, chemotherapy, or both might be used to shrink the tumor before or after surgery.Radiation therapy uses high energy rays (like x-rays) to kill cancer cells and shrink tumors. The radiation may come from outside the body (external radiation) or from radioactive materials put right into the tumor (internal or implant radiation).Other kinds of treatment you might hear about include hormone therapy,stem cell or bone marrow transplant, immunotherapy, andtargeted therapy. Hormone therapy is sometimes used to treat certain kinds ofprostateand breast cancers. Immunotherapy is treatment designed to boost the cancer patients own immune system to help fight the cancer. Targeted therapy is treatment that targets the cancer cells and causes less damage to healthy cells.

Classification of anticancer agents

1. Cytotoxic drugs (Drugs acting directly on cells)

Alkylating agents Alkylating agents involve reactions with guanine in DNA. These drugs add methyl or other alkyl groups onto molecules where they do not belong. This in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA.In the first mechanism an alkylating agent attaches alkyl groups to DNA bases. This alteration results in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases.A second mechanism by which alkylating agents cause DNA damage is the formation of cross-bridges, bonds between atoms in the DNA. In this process, two bases are linked together by an alkylating agent that has two DNA binding sites. Cross-linking prevents DNA from being separated for synthesis or transcription.The third mechanism of action of alkylating agents causes the mispairing of the nucleotides leading to mutations.Examples of alkylating agents: nitrogen mustards; alkyl sulfonates and triazenes.

Antimetabolites:Methotrexate

Methotrexate inhibits folic acid reductase which is responsible for the conversion of folic acid to tetrahydrofolic acid.Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it thinking that it is folic acid. In fact, methotrexate looks so good to the enzyme that it binds to it quite strongly and inhibits the enzyme. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Again, without DNA, no cell division.

Vinca Alkaloids

Plant alkaloids likevincristineprevent cell division, or mitosis. There are several phases of mitosis, one of which is the metaphase. During metaphase, the cell pulls duplicated DNA chromosomes to either side of the parent cell in structures called "spindles". These spindles ensure that each new cell gets a full set of DNA. Spindles are microtubular fibers formed with the help of the protein "tubulin". Vincristine binds to tubulin, thus preventing the formation of spindles and cell division.

2. Hormonal drugs

It involves the manipulation of theendocrine systemthrough exogenous administration of specifichormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones (hormone antagonists).Because steroid hormones are powerful drivers ofgene expression in certain cancercells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergocell death. Examples of drugs altering hormonal milieu: Estrogen (fosfestrol).

3.Targeted drugsWhat are targeted cancer therapies?

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules ("molecular targets") that are involved in the growth, progression, and spread of cancer.Most targeted therapies are either small molecules ormonoclonal antibodies.Small-molecule compoundsare typically developed for targets that are located inside the cell because such agents are able to enter cells relatively easily. Monoclonal antibodies are relatively large and generally cannot enter cells, so they are used only for targets that are outside cells or on the cell surface. Targeted therapies differ from standard chemotherapy in several ways: Targeted therapies act on specific molecular targets that are associated with cancer, whereas most standard chemotherapies act on all rapidly dividing normal and cancerous cells. Targeted therapies are deliberately chosen or designed to interact with their target, whereas many standard chemotherapies were identified because they kill cells. Targeted therapies are often cytostatic (that is, they block tumor cell proliferation), whereas standard chemotherapy agents are cytotoxic (that is, they kill tumor cells).

How are targets for targeted cancer therapies identified?

The development of targeted therapies requires the identification of good targets (targets that play a key role in cancer cell growth and survival).One approach to identify potential targets is to compare the amounts of individual proteins in cancer cells with those in normal cells. Proteins that are present in cancer cells but not normal cells or that are more abundant in cancer cells would be potential targets, especially if they are known to be involved in cell growth or survival. An example of such a differentially expressed target is the human epidermal growth factor receptor 2 protein (HER-2). HER-2 is expressed at high levels on the surface of some cancer cells. Another approach to identify potential targets is to determine whether cancer cells produce mutant (altered) proteins that drive cancer progression. For example, the cell growth signaling protein BRAF is present in an altered form (known as BRAF V600E) in many melanomas

What are the side effects of targeted cancer therapies?

Scientists had expected that targeted cancer therapies would be less toxic than traditional chemotherapy drugs because cancer cells are more dependent on the targets than are normal cells. However, targeted cancer therapies can have substantial side effects. The most common side effects seen with targeted therapies are diarrhea and liver problems. Other side effects seen with targeted therapies include: Skin problems, Problems with blood clotting and wound healing.

Example of targeted cancer therapy (Angiogenesis Inhibitors)

What is angiogenesis? Angiogenesis is the formation of new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells, which line