7. Anti-Cancer drugs

Cancer

A group of diseases in which abnormal cells grow out of control and can spread to other areas of the body

Protooncogenes

Normal genes involved in cell differentiation and division; they regulate cell death (apoptosis)

Oncogene

A mutated proto-oncogene that affects cellular growth-control proteins and triggers unregulated cell division

Tumor-suppressor (TS) genes

Genes that signal a cell to stop multiplying and stop the action of oncogenes. Uncontrollable cell growth can occur if TS genes become lost or dysfunctional

Human papillomavirus (HPV)

Associated with invasive cervical cancer.

Epstein-Barr virus (EBV)

Implicated in Burkitt lymphoma (Central Africa) and nasopharyngeal cancer

Hepatitis B and C viruses

Linked to hepatocellular carcinoma (liver cancer)

Cell cycle–nonspecific (CCNS) drugs

• Act during any phase of the cell cycle, including the G0 (resting) phase.

• Include alkylating drugs, antitumor antibiotics, and hormones

Cell cycle–specific (CCS) drugs

• Act during a specific phase or phases of the cell cycle.

• Most effective against rapidly growing cancer cells.

• Include antimetabolites (S phase), vinca alkaloids (M phase), taxanes (M phase), and topoisomerase I inhibitors (S phase)

Cancer Chemotherapy

Involves using chemicals to kill cancer cells

NOT selective

Anticancer drugs are______so both cancer cells and normal cells are affected, leading to various side effects

Adjuvant therapy

Types of Chemotherapy Usage

Surgery is done first, followed by chemotherapy to eliminate residual tumor cells (microscopic metastases)

Example: Breast cancer and colon cancer

Neoadjuvant therapy

Types of Chemotherapy Usage

Chemotherapy is done first to help a large tumor shrink, making it easier to remove surgically

Palliative chemotherapy

Types of Chemotherapy Usage

Chemotherapy is done to relieve symptoms associated with advanced disease and improve quality of life, not necessarily to cure

Combination chemotherapy

Types of Chemotherapy Usage

Using two or more chemotherapy drugs at a time. This approach is often more effective due to synergistic actions and targeting different mechanisms

General Side Effects and Adverse Reactions (Emphasize: interventions for each)

• Bone Marrow Suppression (Myelosuppression):

  • Low RBC count (Anemia): Rest, RBC transfusion if severe.

  • Low WBC count (Neutropenia): Risk for infection, strict hand hygiene, isolation precautions (reverse isolation/protective environment), avoid crowded places, report fever promptly.

  • Low platelet count (Thrombocytopenia): Risk for bleeding, avoid injury, soft toothbrush, electric razor, avoid IM injections if possible, monitor for signs of bleeding (bruising, petechiae, blood in urine/stool).

• GI Disturbances:

  • Anorexia: Encourage adequate/balanced diet, small frequent meals, nutritional supplements.

  • Nausea and vomiting: Administer antiemetic prior to chemotherapy and regularly as prescribed, ensure adequate hydration.

  • Diarrhea: Low-fiber diet, adequate fluid intake, anti-diarrheal medications as prescribed, perianal skin care.

  • Mucositis (Stomatitis): Frequent oral hygiene with soft brush, saline gargle; avoid alcohol-based mouthwashes, spicy/acidic foods, and extreme temperatures.

• Other:

  • Alopecia (hair loss): Reversible; inform patient, suggest wigs/scarves.

  • Fatigue: Encourage rest, prioritize activities, balanced nutrition.

  • Cachexia syndrome (wasting): Nutritional support, high-calorie/protein diet, appetite stimulants.

  • Infertility: Discuss potential for temporary or permanent infertility, offer fertility preservation options if desired and feasible before treatment.

ALKYLATING DRUGS

work by forming covalent bonds (alkyl groups) with DNA, primarily at guanine bases. This leads to cross-linking of DNA strands, abnormal base pairing, or strand breaks, which inhibits DNA replication and transcription of DNA into RNA, thereby stopping protein synthesis and ultimately leading to cell death. They are cell cycle–nonspecific (CCNS)

Nitrogen Mustards

ALKYLATING DRUGS

Cyclophosphamide: Palliative chemotherapy in lung and lymphomas, multiple myeloma, leukemias, mycosis fungoides, breast cancers, neuroblastoma

Nitrosoureas

ALKYLATING DRUGS

Lomustine: Can cross the blood-brain barrier and treat primary and metastatic brain tumors

Alkyl Sulfonates

ALKYLATING DRUGS

Busulfan: Patients undergoing bone marrow transplantation for acute myeloid leukemia and nonmalignant diseases.

Triazines

ALKYLATING DRUGS

Procarbazine: Stage III and stage IV Hodgkin’s disease

Ethylenimines

ALKYLATING DRUGS

Altretamine: Persistent or recurrent ovarian cancer.

Platinum-containing antineoplastic agents

ALKYLATING DRUGS

(Though not true alkylating agents, they act similarly by forming platinum-DNA adducts that lead to cross-linking and DNA damage.)

• Cisplatin: Metastatic testicular tumors, metastatic ovarian tumors, and advanced bladder cancer.

• Carboplatin: Ovarian carcinoma

ANTIMETABOLITES

are types of chemotherapy treatments that are structurally very similar to normal substances (metabolites) within the cell, particularly those involved in DNA and RNA synthesis. They interfere with various metabolic pathways, especially during the S phase of the cell cycle, by either acting as false building blocks for DNA/RNA or by inhibiting enzymes essential for nucleotide synthesis. This ultimately halts cell division and leads to cell death

Folate Antimetabolite

ANTIMETABOLITES

Methotrexate:

• Mechanism of Action: A folic acid analog that competitively inhibits dihydrofolate reductase (DHFR), an enzyme essential for converting dihydrofolate to tetrahydrofolate, a coenzyme required for purine and pyrimidine synthesis. By blocking DHFR, methotrexate inhibits DNA, RNA, and protein synthesis, particularly in rapidly dividing cells.

• Indications: Malignant and nonmalignant conditions (e.g., rheumatoid arthritis, psoriasis); leukemias and cancers of the GI tract, head and neck, breast, and ovaries; ectopic pregnancies.

Pyrimidine

ANTIMETABOLITES

Fluorouracil (5-FU):

• Mechanism of Action: A pyrimidine analog that is metabolized into several active forms. One key metabolite, FdUMP, inhibits thymidylate synthase, an enzyme critical for pyrimidine synthesis. This leads to "thymineless death" by inhibiting DNA replication. Other metabolites can be incorporated into RNA and DNA, leading to dysfunctional nucleic acids.

• Indications: Cancers of the GI tract, head and neck, colorectal, breast; Actinic keratosis, Basal cell carcinoma.

Purine

ANTIMETABOLITES

Mercaptopurine (6-MP):

• Mechanism of Action: A purine analog that is converted into various active metabolites, primarily 6-thioguanosine monophosphate (6-TGMP). These metabolites inhibit de novo purine synthesis and can be incorporated into DNA and RNA, leading to dysfunctional nucleic acids and ultimately cell cycle arrest and apoptosis.

• Indications: Acute lymphoblastic leukemia; Non-neoplastic conditions: immunosuppression, prevention of organ transplant rejection, treatment of autoimmune diseases (e.g., inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis).

ANTITUMOR ANTIBIOTICS

Mechanism of Action: These are a type of anticancer drug derived from microbial fermentation products. They block cell growth by interfering with DNA, often through intercalation (inserting into the DNA helix), inhibition of topoisomerase enzymes, or generation of free radicals, leading to DNA damage and ultimately cell death. They are cell cycle–nonspecific (CCNS)

Anthracyclines

ANTITUMOR ANTIBIOTICS

• Mechanism of Action: Anti-tumor antibiotics that interfere with enzymes involved in copying DNA (topoisomerase II). They intercalate with DNA (insert between DNA base pairs), which unwinds the DNA helix, preventing DNA replication and transcription. They also generate free radicals that damage DNA.

• Doxorubicin: It slows or stops the growth of cancer cells by blocking an enzyme called topoisomerase.

Chromomycin A3 or Toyomycin: (Plicamycin is a related drug)

ANTITUMOR ANTIBIOTICS

• Plicamycin:

  • Mechanism of Action: Binds to DNA in the presence of magnesium ions, disrupting DNA-dependent RNA synthesis. It also inhibits the action of parathyroid hormone and osteoclast activity, leading to decreased calcium levels.

  • Indications: Used to treat testicular cancer, Paget's disease of bone, and, rarely, the management of hypercalcemia associated with malignancy.

Miscellaneous

ANTITUMOR ANTIBIOTICS

Bleomycin:

• Mechanism of Action: Acts by inducing DNA strand breaks through the formation of free radicals and direct oxidative damage. This leads to fragmentation of DNA and inhibition of DNA synthesis. It is cell cycle-specific, acting primarily in the G2 and M phases.

• Indications: Used to treat Hodgkin's lymphoma, non-Hodgkin's lymphoma, testicular cancer, ovarian cancer, and cervical cancer among others

ALKALOIDS

Traditionally defined as nitrogen-containing organic constituents that occur mainly in plants. They are anti-tumor agents

Vinca Alkaloids

Mechanism of Action: A subset of drugs obtained from the Madagascar periwinkle plant (Catharanthus roseus). They are cell cycle-specific, acting in the M phase (mitosis). They bind to tubulin, a protein essential for the formation of microtubules. This binding disrupts the formation of the mitotic spindle, leading to metaphase arrest and subsequently apoptosis.

Vinblastine (VBL)

Vinca Alkaloids:

Has been used as an integral part of medicinal treatment regimens for testicular carcinoma and both Hodgkin and non-Hodgkin lymphomas

Vinorelbine (VRL)

Vinca Alkaloids:

similar to VBL, it has significant anti-tumor activity in patients with breast cancer and can be affected on bone tumor cells, osteosarcoma.

Vincristine (VCR)

Vinca Alkaloids:

Has been approved to treat acute leukemia, rhabdomyosarcoma, neuroblastoma, Wilm's tumor, Hodgkin's disease and other lymphomas

Podophyllum Alkaloids / Topoisomerase Inhibitors

• Mechanism of Action (Podophyllotoxin, specific for warts): Is an antimitotic agent. It acts by preventing viral wart cells from dividing and multiplying by binding to tubulin and inhibiting microtubule assembly, similar to vinca alkaloids. Eventually, all the wart cells die, and new healthy cells grow in their place.

• Indications: Used in treatment of small cell carcinoma of lung, prostate and testicular carcinomas (for derivatives like etoposide/teniposide). Used to remove benign growth (e.g., genital warts for podophyllotoxin)

HORMONES AND HORMONAL AGONIST AND ANTAGONIST

work by either adding hormones, blocking hormone production, or blocking hormone receptors. They aim to slow the growth of hormone-dependent tumors by preventing cancer cells from using or producing hormones essential for their growth

Glucocorticoids (Corticosteroids)

• Mechanism of Action: Assist with protein metabolism. They are potent anti-inflammatory and immunosuppressive agents. In cancer, they induce apoptosis in certain lymphoid malignancies (e.g., leukemias, lymphomas) and reduce inflammation and edema associated with tumors. They also suppress the immune system.

• Examples: Prednisone (most common steroid prescribed and is four times as potent as glucocorticoid), Methylprednisolone, Hydrocortisone, Dexamethasone.

• Indications: Used to treat patients with leukemias, multiple myeloma, inflammatory bowel disease, and transplant rejection.

• AE: Delirium, elevated serum glucose, insomnia, irritability, and other psychological problems; fluid retention, muscle weakness, irregular menstrual bleeding, atherosclerosis, and thrombosis among others

Mineralocorticoids (Corticosteroids)

(Less relevant directly to anticancer therapy, but a class of steroids)

Sex Hormones

Used to slow the growth of hormone-dependent tumors (for prostate cancer and breast cancer)

Exogenous estrogens

• Mechanism of Action: In prostate cancer, estrogens can suppress the production of luteinizing hormone (LH) from the pituitary, which in turn reduces testosterone production from the testes, thereby slowing the growth of androgen-dependent prostate cancer cells. In postmenopausal breast cancer, high doses of estrogens can sometimes exert an anti-estrogenic effect or trigger tumor cell differentiation/apoptosis.

• Indications: Most effective for palliative treatment of breast cancer among postmenopausal women (though less common now with other options). Estrogen therapy used as a palliative treatment to slow down the progression of prostatic cancer by decreasing testosterone production. Used for the improvement of bone metastasis.

• Example: Conjugated estrogens

Synthetic Progestins

• Mechanism of Action: The exact mechanism in cancer is not fully understood but may involve anti-estrogenic effects, modulation of hormone receptors, or direct cytotoxic effects.

• Indications: Used for renal and endometrial cancers.

• Examples: Hydroxyprogesterone Caproate, Megestrol, Medroxyprogesterone Acetate.

• AE of Progestins and Estrogens: Fluid retention, thrombosis, menstrual irregularities, osteoporosis.

Antiandrogens

• Mechanism of Action: Block the effects of testosterone by competitively binding to androgen receptors on cancer cells, thereby slowing or shrinking androgen-dependent cancers (primarily prostate cancer).

• Examples: Bicalutamide, Flutamide

Antiestrogens

• Mechanism of Action: Block the effects of estrogen by competitively binding to estrogen receptors on cancer cells, thereby slowing or shrinking estrogen-dependent cancers (primarily breast cancer).

• Example: Fulvestrant (a pure antiestrogen that degrades the estrogen receptor).

Selective Estrogen Receptor Modulators (SERMs)

• Mechanism of Action: Act as antagonists on estrogen receptors in breast tissue, thereby inhibiting the growth of estrogen-receptor-positive breast cancer cells. However, they can act as agonists on estrogen receptors in other tissues (e.g., bone, uterus).

• Tamoxifen: Primarily used for breast cancer in both men and women (especially ER-positive)

Luteinizing Hormone-Releasing Hormone (LHRH) Agonists / Gonadotropin-Releasing Hormone (GnRH) Analogues/Agonists

• Mechanism of Action: Initially stimulate, but then suppress (through desensitization of the pituitary gland), the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. This leads to a significant decrease in testosterone production from the testes (in men) and estrogen production from the ovaries (in premenopausal women), effectively achieving medical castration and starving hormone-sensitive cancers.

• Examples: Leuprolide, Goserelin

Aromatase Inhibitors

• Mechanism of Action: Drugs that stop the enzyme aromatase from converting other hormones (like androgens) into estrogen in peripheral tissues. This significantly reduces circulating estrogen levels, particularly in postmenopausal women (where ovarian estrogen production has ceased). This is crucial for treating hormonally sensitive breast cancer.

• Indications: Used in the treatment of hormonally sensitive breast cancer in postmenopausal women and premenopausal women who have had their ovaries removed (as their main source of estrogen is now peripheral conversion).

• Examples: Anastrozole, Letrozole, Exemestane.

MISCELLANEOUS CHEMOTHERAPY AGENTS

Hepatitis B vaccine

• Mechanism of Action: A recombinant subunit vaccine containing the Hepatitis B surface antigen (HBsAg). When administered, it stimulates the production of protective antibodies against HBsAg, preventing infection with the hepatitis B virus.

• Action: To prevent infection with the hepatitis B virus, which can cause liver cancer (hepatocellular carcinoma).

• Route: IM.

MISCELLANEOUS CHEMOTHERAPY AGENTS

Gardasil and Cervarix (HPV vaccines)

• Mechanism of Action: Recombinant subunit vaccines containing virus-like particles (VLPs) of specific HPV types. These VLPs resemble the natural virus but lack genetic material, so they cannot cause infection. They stimulate a strong humoral immune response (antibody production) that protects against subsequent HPV infection.

• Action: To prevent HPV infections that can cause cervical cancer, as well as vaginal, vulvar, anal, and oropharyngeal cancers (depending on the vaccine's valency).

• Route: IM.