Cancer, Tumors, and Metastasis

• Cancer refers to diseases characterized by uncontrolled cell division and the ability to invade other tissues, resulting from DNA mutations.
• Metastasis is the spread of cancer cells to other body parts.
• A cyst is an abnormal sac or closed cavity filled with liquid or semisolid matter and is not a tumor or cancer.
• A tumor, also known as a neoplasm, is a mass observed as a hard lump in the body.
• Inflammatory breast cancer is one example of a type of cancer that may not present with a tumor.

Inflammatory Breast Cancer

• Signs and symptoms include sudden breast enlargement, skin discoloration, nipple retraction, tenderness, pain, and an orange peel-like texture.

Benign vs. Malignant Tumors

• Benign tumors do not metastasize or invade surrounding tissues and are non-cancerous.
• Malignant tumors can invade and spread throughout the body and are cancerous.

Steps of Metastasis

• Cancer cells melt collagen and connective tissue for entry into the circulatory system.
• Intravasation describes cancer cells invading the lymphatic and circulatory systems.
• Extravasation is the process of cancer cells attaching to other parts of the body.
• Angiogenesis is the growth of new blood vessels to supply nutrients to cancer cells due to their rapid growth.
• Cancer cells that travel to other organs remain the same type of cancer cell; for example, breast cancer cells in the lungs are still breast cancer cells, not lung cancer cells.

Cancer Treatments

• Established cancer treatments include surgery, radiation therapy, chemotherapy, hormone therapy, and stem cell transplants.
• Radiation therapy uses radiation sources directed at the cancerous body part.
• Chemotherapy uses cytotoxic and other drugs to treat cancer.
• A mastectomy, or breast removal, is a surgical example of cancer treatment.

Goals of Chemotherapy

• Palliation alleviates symptoms and prolongs life.
• Cure is the complete eradication of cancer, with early detection being key.
• Adjuvant chemotherapy is an additional treatment after the initial treatment.
• Neoadjuvant chemotherapy is an additional treatment conducted before the initial treatment.

Common Chemotherapy Side Effects

• Hair loss occurs because chemotherapy targets rapidly regenerating hair follicles.
• Loss of appetite, nausea, vomiting, and diarrhea result from effects on fast-growing cells in the gastrointestinal tract.
• Bone marrow suppression occurs due to the impact on rapidly dividing blood cells, leading to decreased blood cell production.
• Fatigue is also a common side effect.

Classes of Chemotherapeutic Agents

• Cell-cycle specific agents (CCSAs) target cancer cells during the cell cycle as they actively divide.
• Cell-cycle non-specific agents (CCNSAs) can target cancer cells in any phase, including the G0 phase.
• Phase-specific CCSAs are effective during a particular phase of the cell cycle.
• Phase non-specific CCSAs are effective against cancer cells within the active cell cycle, regardless of the phase.

Agents by Cell Cycle Phase

• Vinca Alkaloids are effective in the M-Phase.
• Asparaginase and Prednisone are effective in the G1 Phase.
• Antimetabolites are effective in the S Phase.
• Bleomycin and Etoposide are effective in the G2 Phase.
• Alkylating Agents, Antitumor Antibiotics, and Cisplatin are effective in any phase of the cell cycle except G0 phase
• Nitrosoureas and Radiation are effective in any phase of the cell cycle, including G0 phase.

Plant Alkaloids

• Plant alkaloids are anti-cancer drugs derived from plants.
• Microtubules are crucial for chromosome migration during cell division, serving as the building blocks of the mitotic spindle.

Microtubule Damaging Agents

• Vinca Alkaloids (Vin-) and Taxanes (-taxel) are classes of drugs that damage microtubules.
• Vinca Alkaloids are isolated from the Catharanthus roseus plant.
• Vinblastine, Vincristine, Vindesine, and Vinorelbine are examples of vinca alkaloids.
• Vinca alkaloids bind to microtubules and promote depolymerization, preventing microtubule rescue.
• Vinblastine is used to treat testicular cancer and has bone marrow suppression as a notable side effect.
• Vincristine is indicated for Hodgkin's Lymphoma and Wilm's Tumor, with neurotoxicity or peripheral neuropathy as a notable side effect.
• Taxanes are derived from the Western yew (Taxus brevifolia) and European yew (Taxus baccata) trees.
• Taxanes bind to and stabilize microtubules by enhancing tubulin polymerization, blocking dynamic instability, and leading to apoptosis.
• Docetaxel targets advanced breast cancer and prostate cancer.
• Ovarian cancer and advanced breast cancer are treated with Paclitaxel.

Topoisomerase Inhibitors

• Podophyllotoxins and Camptothecins are two classes of drugs that inhibit topoisomerase.
• Topoisomerases break, unwind, and reseal tangled DNA strands for DNA replication and RNA transcription.
• Podophyllotoxins inhibit topoisomerase II, causing double-strand DNA breaks.
• Podophyllotoxins are sourced from the Podophyllum peltatum plant.
• Etoposide, a Podophyllotoxin, targets the G2 phase and is indicated for monocytic leukemia, testicular cancer, and lung carcinoma.
• Teniposide, a Podophyllotoxin, targets the late S and early G2 phases and is indicated for lymphomas.
• Myelosuppression and lymphoid system toxicity are notable side effects of Podophyllotoxins.
• Camptothecins are derived from Camptotheca acuminate.
• Camptothecins inhibit topoisomerase I.
• Topotecan is indicated for metastatic ovarian cancer and cisplatin-resistant neoplasms.
• SN-38 is the active metabolite of Irinotecan and inhibits topoisomerase I.
• Irinotecan is used for colon rectal cancer and has early and late forms of diarrhea as side effects.

Irinotecan Diarrhea

• Early form diarrhea occurs within 24 hours due to a cholinergic effect and is treated with atropine.
• Late form diarrhea is caused by SN-38, which induces mucosal damage with rate and electrolyte malabsorption and is treated with loperamide.
• UDP-glucuronosyl transferase 1A1 metabolizes SN-38 to its inactive form.
• Irinotecan is contraindicated in patients with Gilbert syndrome because of UDP-glucuronosyl transferase 1A1 abnormalities.
• Patients with Gilbert Syndrome may experience increased Irinotecan toxicity and jaundice.

Anthracyclines

• Anthracyclines are derived from Streptomyces peucetius var. caesius.
• Anthracyclines work in the S Phase.
• Anthracyclines prevent topoisomerase from reattaching broken DNA ends and cause additional DNA strand breaks through intercalation.
• Doxorubicin is indicated for breast, ovarian, thyroid, and lung cancers, as well as acute leukemia.
• Daunorubicin and Idarubicin treat acute leukemia.
• Red or orange urine discoloration and cardiotoxicity are adverse effects of Anthracyclines.

Dactinomycin

• Dactinomycin intercalates guanine-cytosine base pairs, inhibiting DNA and RNA synthesis.
• Dactinomycin is used for pediatric cancers such as Wilms tumor and kidney cancer.
• Radiation recall and potent vesicant properties are notable side effects of Dactinomycin.

Plicamycin

• Plicamycin, formerly known as Mithramycin, is sourced from Streptomyces plicatus.
• It binds to DNA in the presence of Mg2+ or other divalent cations and interrupts RNA synthesis.
• Plicamycin is used in the treatment of testicular cancer.

Mitomycin

• Mitomycin is derived from Streptomyces caespitosus.
• It causes DNA cross-linking and abnormal base pairing, specifically with guanine.
• Mitomycin is converted to a metabolite responsible for cross-linking.
• Mitomycin can be used as a second-line agent for metastatic colon cancer, cervical cancer (with Bleomycin and Vincristine), and stomach, pancreas, and lung cancer (with Doxorubicin and 5-Fluorouracil).

Bleomycin

• Bleomycin comes from Streptomyces verticillus.
• It causes DNA strand breaks due to oxidation of the DNA-bleomycin-Fe(II) complex, producing toxic free radicals that inhibit DNA synthesis.