Chemotherapy Mechanisms and Drug Effects

Cancer is a disease characterized by a defect in the normal control mechanisms of cell survival, proliferation, and differentiation. The abnormal cells invade surrounding tissues and can spread to distant sites. The disease can result in tumor-related symptoms and eventually death if not eradicated.

Cancer cells are more vulnerable to treatment when they are actively dividing. Therefore, drugs targeting specific cell cycle phases are most effective during active proliferation.

Cell cycle-nonspecific drugs kill tumor cells regardless of their activity. They can target cells in both active and resting phases of the cell cycle, but are most effective when there is a large proportion of proliferating cells.

Increased DNA repair in tumor cells can make them resistant to chemotherapy drugs. This mechanism is particularly important in drugs that damage DNA, like alkylating agents and cisplatin.

Some tumor cells increase the production of thiol trapping agents, like glutathione, which interact with drugs forming reactive species. This mechanism is seen with drugs like bleomycin, cisplatin, and anthracyclines.

Resistance can also arise from changes in the target enzyme. For instance, in the case of methotrexate, increased production of dihydrofolate reductase can render the drug less effective.

Environmental exposures, such as ionizing radiation and chemical carcinogens, play a major role in cancer development. Common examples include tobacco smoke, azo dyes, aflatoxins, asbestos, and benzene.

Certain viruses, such as hepatitis B and C, Epstein-Barr virus, and HIV, are associated with different forms of cancer. These viruses can introduce genetic material or alter cellular pathways that contribute to cancer development.

Cancer cells may have increased activity of enzymes that inactivate anticancer drugs. This makes the drugs less effective.

Cancer cells may have decreased activity of enzymes that convert prodrugs into their active, cytotoxic forms. This can make the prodrugs less effective.

Cancer cells can pump out anticancer drugs using a protein called P-glycoprotein. This prevents the drug from accumulating inside the cell.

Chemotherapy given before the primary treatment (like surgery or radiation) to shrink the tumor and make the primary treatment more effective.

Chemotherapy given after the primary treatment (like surgery or radiation) to reduce the risk of recurrence.

Alkylating agents are a class of chemotherapy drugs that damage DNA by adding alkyl groups. This stops cancer cells from replicating.

Primary induction chemotherapy is the first-line treatment for many cancers, especially those that are advanced or aggressive.

Chemotherapy drugs are used as an adjuvant to local treatments (surgery or radiation) to reduce the risk of cancer coming back.

Cell cycle-nonspecific drugs like alkylating agents damage DNA by forming reactive species that attach to DNA bases, disrupting DNA replication and causing cell death. They are less selective for dividing cells and can impact both actively proliferating and resting cells, but are more effective when there are many dividing cells.

CCNS drugs can be ineffective if cancer cells develop ways to repair DNA damage, get rid of the drug faster, or produce substances that counter the drug's effect.

Antimetabolites are drugs structurally similar to essential building blocks for DNA and RNA, interfering with their synthesis and causing cancer cells to die.

Methotrexate blocks the enzyme dihydrofolate reductase (DHF reductase), preventing the synthesis of essential components for DNA and protein production, hindering cell growth.

Methotrexate can have adverse effects on rapidly dividing normal cells, causing side effects like bone marrow suppression, skin problems, and gastrointestinal issues.

Leucovorin rescue involves giving folinic acid (leucovorin) to reduce the toxic effects of methotrexate on normal cells, allowing normal cells to recover from the drug's effects.

Fluorouracil (5-FU) is converted into a molecule that inhibits thymidylate synthase, an enzyme crucial for DNA synthesis, leading to cell death by depriving them of thymine.

Cytarabine (ARA-C) is a pyrimidine antimetabolite that specifically targets cancer cells during their S phase (DNA replication).

An analog of deoxycytidine that inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase.

A class of antineoplastic drugs derived from plants, known for their ability to disrupt microtubule assembly, thus interfering with cell division.

A group of drugs that inhibit the formation of the mitotic spindle by preventing the assembly of tubulin dimers into microtubules. They halt cell division by blocking the formation of the structure that pulls chromosomes apart.

Drugs that induce DNA breakage by inhibiting topoisomerase II, an enzyme involved in DNA unwinding and replication.

Drugs that damage DNA by inhibiting topoisomerase I, an enzyme crucial for DNA repair processes.

Drugs that interfere with the mitotic spindle by preventing microtubule disassembly. They 'freeze' the spindle, preventing cell division.

A diverse group of antineoplastic drugs that include anthracyclines, bleomycin, and mitomycin. These drugs have various mechanisms of action.

A type of antibiotic antineoplastic drug known for its effectiveness against various cancer types. They work by inhibiting DNA replication and cell division.

Gefitinib and erlotinib are medications that block the EGFR tyrosine kinase domain, preventing the receptor from activating downstream signaling pathways that promote cell growth and survival in cancer cells.

Bevacizumab is a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), preventing it from interacting with VEGF receptors and inhibiting angiogenesis, a process crucial for tumor growth and metastasis.

Rituximab is a monoclonal antibody that targets a surface protein on non-Hodgkin's lymphoma cells, leading to their destruction through various mechanisms like complement-mediated lysis, direct cytotoxicity, and apoptosis induction.

Tamoxifen is a selective estrogen receptor modulator that blocks estrogen binding to receptors in estrogen-sensitive breast cancer cells, inhibiting their growth. It's also prescribed for women at a high risk for breast cancer to prevent its development.

Toremifene is a newer estrogen receptor antagonist used in treating advanced breast cancer. It acts by blocking the binding of estrogen to its receptor, thereby inhibiting the growth of estrogen-sensitive breast cancer cells.

Flutamide is an androgen receptor antagonist used in prostatic carcinoma. It prevents the binding of androgens, like testosterone, to their receptors, inhibiting the growth of prostate cancer cells.

Leuprolide analogs, like Goserelin and Nafarelin, are GnRH agonists that, when administered constantly, inhibit the release of gonadotropins (LH and FSH) from the pituitary gland. This ultimately reduces the production of testosterone, crucial for prostate cancer growth.

Onansetron and Metoclopramide are 5-HT3 antagonists used to treat nausea and vomiting caused by chemotherapy. They block the action of serotonin in the brain, reducing the triggering of nausea and vomiting.

Anthracyclines are a group of anticancer drugs that target DNA replication and cell division. They work by intercalating between DNA base pairs, inhibiting topoisomerase II, generating free radicals, and causing DNA strand scission. These drugs also disrupt cell membranes.

Bleomycin is a glycopeptide antibiotic that acts primarily during the G2 phase of the cell cycle. It generates free radicals and binds to DNA, leading to strand breaks and inhibition of DNA synthesis.

Mitomycin is a CCNS drug that is metabolized by liver enzymes into an alkylating agent. This agent cross-links DNA strands, preventing proper cell division and leading to cell death.

Imatinib is a tyrosine kinase inhibitor that selectively targets the bcr-abl oncogene found in chronic myeloid leukemia (CML). By blocking the tyrosine kinase activity, Imatinib prevents the activation of phosphorylated proteins and disrupts the transmission of proliferative signals to the nucleus, ultimately leading to leukemic cell apoptosis.

Trastuzumab is a monoclonal antibody that targets the HER-2/neu receptor, a protein that is overexpressed in some breast cancers. By binding to this receptor, Trastuzumab inhibits cell growth and promotes cell death.

Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor (EGFR), which is found on the surface of some cancer cells. By binding to EGFR, Cetuximab blocks the binding of epidermal growth factor and ultimately inhibits cell growth.

Panitumumab is a fully human monoclonal antibody that targets the epidermal growth factor (EGF). By binding to EGF, Panitumumab prevents it from binding to the EGFR receptor on cancer cells, thus inhibiting cell growth.

Growth factor receptor inhibitors are a class of targeted therapy drugs that aim to block the function of receptors that promote cell growth. They are often used in the treatment of cancers that overexpress these receptors.