Podcast
Questions and Answers
What is the primary significance of metastasis formation in cancer progression?
What is the primary significance of metastasis formation in cancer progression?
Which process is essential for both tumor growth and the ability to metastasize?
Which process is essential for both tumor growth and the ability to metastasize?
Which of the following compounds is primarily used as a chemoprotective agent to reduce the toxic side effects of cyclophosphamide?
Which of the following compounds is primarily used as a chemoprotective agent to reduce the toxic side effects of cyclophosphamide?
What are the primary characteristics of carcinoma, which makes up 80% of tumors?
What are the primary characteristics of carcinoma, which makes up 80% of tumors?
Signup and view all the answers
What mechanism do alkylating agents primarily use to exert their cytotoxic effects?
What mechanism do alkylating agents primarily use to exert their cytotoxic effects?
Signup and view all the answers
Which class of cancer treatment specifically aims to alter the growth or survival of tumor cells?
Which class of cancer treatment specifically aims to alter the growth or survival of tumor cells?
Signup and view all the answers
Which of the following is a specific toxicity associated with the use of cyclophosphamide?
Which of the following is a specific toxicity associated with the use of cyclophosphamide?
Signup and view all the answers
What type of treatment is characterized by activating the immune system against cancer cells?
What type of treatment is characterized by activating the immune system against cancer cells?
Signup and view all the answers
Which of the following agents is indicated for the treatment of brain tumors?
Which of the following agents is indicated for the treatment of brain tumors?
Signup and view all the answers
What is the function of cytochrome P450 in the metabolism of cyclophosphamide?
What is the function of cytochrome P450 in the metabolism of cyclophosphamide?
Signup and view all the answers
Which drug is specifically used for colorectal cancer treatment after fluorouracil therapy?
Which drug is specifically used for colorectal cancer treatment after fluorouracil therapy?
Signup and view all the answers
Which of the following is NOT a type of microtubule inhibitor?
Which of the following is NOT a type of microtubule inhibitor?
Signup and view all the answers
What is a common adverse effect of taxanes such as Paclitaxel?
What is a common adverse effect of taxanes such as Paclitaxel?
Signup and view all the answers
What condition is Teniposide primarily used to treat?
What condition is Teniposide primarily used to treat?
Signup and view all the answers
Which enzyme family do PARP inhibitors, like Olaparib, primarily target for cancer treatment?
Which enzyme family do PARP inhibitors, like Olaparib, primarily target for cancer treatment?
Signup and view all the answers
What is a primary clinical use of Docetaxel?
What is a primary clinical use of Docetaxel?
Signup and view all the answers
Which drug is classified as a topoisomerase I inhibitor?
Which drug is classified as a topoisomerase I inhibitor?
Signup and view all the answers
Which agriculture source is linked to the production of Vincristine?
Which agriculture source is linked to the production of Vincristine?
Signup and view all the answers
Which of the following drugs is primarily indicated for the treatment of advanced sarcoma of soft tissues?
Which of the following drugs is primarily indicated for the treatment of advanced sarcoma of soft tissues?
Signup and view all the answers
Which process is mainly inhibited by drugs that intercalate with DNA?
Which process is mainly inhibited by drugs that intercalate with DNA?
Signup and view all the answers
What is a significant toxicity associated with Doxorubicin?
What is a significant toxicity associated with Doxorubicin?
Signup and view all the answers
Which of the following drugs is considered a purine antagonist?
Which of the following drugs is considered a purine antagonist?
Signup and view all the answers
What type of cell is most likely to experience myelotoxicity from DNA-damaging drugs?
What type of cell is most likely to experience myelotoxicity from DNA-damaging drugs?
Signup and view all the answers
What is the mechanism of action of Doxorubicin?
What is the mechanism of action of Doxorubicin?
Signup and view all the answers
Which of the following agents works through intercalation with DNA?
Which of the following agents works through intercalation with DNA?
Signup and view all the answers
What is a potential consequence of using drugs that affect DNA synthesis and stability?
What is a potential consequence of using drugs that affect DNA synthesis and stability?
Signup and view all the answers
What is the primary genetic change that leads to the transformation of proto-oncogenes into oncogenes?
What is the primary genetic change that leads to the transformation of proto-oncogenes into oncogenes?
Signup and view all the answers
Which phase of the cell cycle do antimetabolites act most effectively?
Which phase of the cell cycle do antimetabolites act most effectively?
Signup and view all the answers
What is the structural role of folates in DNA synthesis?
What is the structural role of folates in DNA synthesis?
Signup and view all the answers
Which of the following is NOT a characteristic that differentiates cancer cells from normal cells?
Which of the following is NOT a characteristic that differentiates cancer cells from normal cells?
Signup and view all the answers
Which term best describes the process by which tumor cells spread from their original site to other parts of the body?
Which term best describes the process by which tumor cells spread from their original site to other parts of the body?
Signup and view all the answers
What role does telomerase play in cancer cell biology?
What role does telomerase play in cancer cell biology?
Signup and view all the answers
Which characteristic of tumor cells enables them to invade surrounding tissues?
Which characteristic of tumor cells enables them to invade surrounding tissues?
Signup and view all the answers
How do mutant tumor suppressor genes contribute to carcinogenesis?
How do mutant tumor suppressor genes contribute to carcinogenesis?
Signup and view all the answers
What is the impact of dedifferentiation on cancer cell function?
What is the impact of dedifferentiation on cancer cell function?
Signup and view all the answers
Which of the following mechanisms is NOT a way cancer cells avoid normal regulatory mechanisms?
Which of the following mechanisms is NOT a way cancer cells avoid normal regulatory mechanisms?
Signup and view all the answers
Which immune checkpoint inhibitors specifically target PD-1?
Which immune checkpoint inhibitors specifically target PD-1?
Signup and view all the answers
What is a common combination treatment for Non-Hodgkin lymphomas?
What is a common combination treatment for Non-Hodgkin lymphomas?
Signup and view all the answers
Which monoclonal antibody is associated with targeting HER2 in breast cancer treatment?
Which monoclonal antibody is associated with targeting HER2 in breast cancer treatment?
Signup and view all the answers
Which treatment is typically included in the regimen for triple-negative breast cancer?
Which treatment is typically included in the regimen for triple-negative breast cancer?
Signup and view all the answers
What is the primary mechanism of immunotherapy in cancer treatment?
What is the primary mechanism of immunotherapy in cancer treatment?
Signup and view all the answers
Which drug is used in the pharmacological treatment of metastatic colon cancer targeting VEGF?
Which drug is used in the pharmacological treatment of metastatic colon cancer targeting VEGF?
Signup and view all the answers
Which treatment regimen includes the use of Fluorouracil in breast cancer therapy?
Which treatment regimen includes the use of Fluorouracil in breast cancer therapy?
Signup and view all the answers
Which immune checkpoint inhibitor is used for treating tumors expressing PDL-1?
Which immune checkpoint inhibitor is used for treating tumors expressing PDL-1?
Signup and view all the answers
What is the role of IFN and IL-2 in the immune response?
What is the role of IFN and IL-2 in the immune response?
Signup and view all the answers
Which chemotherapy agents are included in the BEP regimen for testicular cancer?
Which chemotherapy agents are included in the BEP regimen for testicular cancer?
Signup and view all the answers
Study Notes
Workshop 7: Antineoplastic Drugs
- Antineoplastic drugs are used to treat cancer
- Cancer is uncontrolled multiplication and spread of abnormal body cells
Neoplasm
- A neoplasm is a mass of tissue formed by abnormal, excessive, uncoordinated, purposeless proliferation of cells
- Abnormal cells are characterized by uncontrolled cell growth, loss of cell differentiation and function, invasiveness, and metastasis.
Pathophysiology of Cancer
- Genesis of Tumor Cells: Cancer occurs due to DNA mutations, mainly through two genetic changes:
- Activation of proto-oncogenes: Proto-oncogenes control cell growth, division, and death. Mutations transform them into oncogenes, thus driving uncontrolled cell growth and malignant transformation.
- Inactivation of Tumor Suppressor Genes: These genes normally prevent cells from becoming cancerous. Mutations lead to the disappearance of these checks and allows for abnormal growth.
- Four Key Characteristics of Cancer Cells:
- Uncontrolled Proliferation: Cancer cells ignore normal cell cycle controls, leading to rapid and unchecked division
- Dedifferentiation and Loss of Function: Cancer cells lose their specialized characteristics and ability to perform their normal functions, becoming less specialized
- Invasiveness: Cancer cells invade surrounding tissues by breaking down the surrounding extracellular membrane
- Metastasis: Cancer cells travel to distant sites throughout the body, establishing secondary tumors
Antineoplastic Therapy
- Drugs to Alter DNA: Cytotoxic drugs target DNA (e.g., alkylating agents, platinum compounds, antibiotics).
- Drugs Interfering with Growth or Survival of Tumor Cells: Targeted therapies are used to fight specific proteins or pathways that enable unregulated cell growth (e.g., hormone-dependent therapies, inhibitors of tyrosine kinases, and angiogenesis inhibitors).
- Drugs Activating the Immune System: Immunotherapy aims to energize the body's immune system in attacking cancer cells (e.g., immune checkpoint inhibitors, and cell therapies)
Cancer Types
- Carcinomas (80% of tumors): Originate from epithelial cells (e.g., lung, breast, colon, prostate)
- Sarcomas: Originate from connective or conjunctive tissues (e.g., muscles, bones, cartilages)
- Leukemias: Cancer of the bone marrow, impacting blood cells (e.g., erythrocytes, leukocytes, platelets).
- Lymphomas: Cancer of the lymphatic system (e.g., lymph nodes and lymphatic organs).
Common Unwanted Effects of Antineoplastic Drugs
- Immediate (few hours): nausea, vomiting, phlebitis, renal failure, anaphylaxis, anorexia, fever, hemorrhagic cystitis
- Precocious (days-weeks): leukopenia, myelosuppression, alopecia, stomatitis, ulcerations, diarrhea, psychosis
- Weeks-months: anemia, aspermia, hyperpigmentation, neuropathies, pulmonary fibrosis, cardiotoxicity
- Delayed (months-years): sterility, carcinogenesis, early menopause, osteoporosis
Strategies for Treatment
- Surgery, Radiotherapy, Chemotherapy and targeted therapies, and Immunotherapy are treatment strategies to target cancer.
Pharmacotherapy Treatment
- Primary therapy: treatment used alone.
- Neoadjuvant therapy: treatment given before surgery.
- Adjuvant therapy: treatment given after surgery.
- Combination therapy: using multiple drugs to improve efficacy and reduce resistance, including several drugs with different mechanisms or actions.
- Minimizing toxicity in normal tissue: using treatment in cycles or metronomic posology to provide the treatment effects while minimizing the adverse effects on normal cells.
Chemotherapy Resistances
- Mechanisms leading to resistance:
- Alteration in membrane transport system (MDR1)
- Increased enzymatic deactivation
- Utilization of alternative pathways
- Apoptosis resistance (mutation p53)
- Reparation of DNA damage (ERCC11)
- Decreased drug accumulation
- Altered drug metabolism and detoxification
- Mutations in drug targets
- Target molecule alteration
- Tumor cells reducing cytotoxic drug accumulation by overexpression of P-glycoprotein.
- Resistance causes by inefficient activation of the drug, rapid repair of lesions, or alteration of the target.
- Modification of the p53 gene and excessive expression of the Bcl-2 gene family contribute to drug resistance.
Therapeutic Strategies
- Alter DNA tumor cells
- Damage DNA
- Affect DNA synthesis and stability
- Alter signals involved in growth and differentiation of tumor cells
- Hormones
- Tumor Pathways
- Immune system activation
- Immune Response
- Checkpoint Inhibitors
- Cell Therapies
- Vaccines
Cytotoxic drugs in the cell cycle
- Cytotoxic drugs act on different phases of the cell cycle.
- Drugs which target DNA synthesis, and integrity.
- Drugs which target DNA damaging agents, for example alkylating agents. Drugs which target DNA repair.
Alkylating Agents
-
Nitrogen Mustard: Cyclophosphamide
-
Nitrosureas: Carmustine, Lomustine
-
Others: Dacarbazine, Temozolamide
-
Mechanism of Action: They damage cancer cell DNA via cross-linking between DNA strands, hindering DNA replication and transcription.
-
Adverse effects: mutagenesis, carcinogenesis, alopecia, depression of bone marrow function and sterility.
Nitrogen Mustards
- Cyclophosphamide: Oral administration, preferred oral route, crosses blood-brain barrier. Active metabolites alkylate DNA via hepatic cytochrome P450 enzyme. Broad spectrum (non-Hodgkin lymphoma, breast, lung cancer). Specific toxicities include hemorrhagic cystitis, neurotoxicity, and hepatic toxicity.
- Metabolism of Cyclophosphamide: Phosphoramide mustard to aldophosphamide to acrolein, leading to hemorrhagic cystitis. Mesna is used to mitigate this effect by creating a sulfur-containing compound which reacts with acrolein.
Nitrosureas
- Carmustine and Lomustine: Cross blood-brain barrier (liposolubility), metabolites appear in the urine, used in brain tumours
Others
- Temozolomide, Dacarbazine: Cross blood-brain barrier, used for specific tumors including malignant melanoma
Platinum Compounds
- Intercalating agents: Cisplatin, Carboplatin
- Mechanism of Action: Intrastrand cross-links between neighboring guanine residues, preventing DNA replication.
Antibiotics-Antraciclines
- Doxorubicin, Daunorubicin
- Mechanism of Action: DNA intercalation, inhibiting DNA and RNA synthesis, generation of free radicals.
- Specific Toxicities: Cardiotoxicity, hyperpigmentation
- Clinical Uses: Breast, bladder, ovarian cancer, sarcomas, carcinomas, Hodgkin lymphoma
Other Intercalating Agents
- Trabectedin: IV administration, monotherapy. Advanced sarcoma and combined therapy with doxorubicin or platinum.
- Mechanism of action: DNA intercalation in tumor cells interrupts the cell cycle, macrophages are involved in the response.
More Effective Drugs in Cells with High Proliferation Rate
- Adverse effects: bone marrow depression (myelotoxicity), fatigue (anemia), developmental delay (growth in children), infertility, teratogenicity, poor wound healing, alopecia, mutagenicity, carcinogenicity, gastrointestinal problems.
Antimetabolites
- Structural analogs of metabolites essential for cell growth and division (e.g., folate, purine, and pyrimidine analogs)
- Folate antagonists: Methotrexate
- Pyrimidine antagonists: 5-fluorouracil, cytarabine, gemcitabine
- Purine antagonists: 6-mercaptopurine, 6-thioguanine, azathioprine
- Mechanisms of action: Inhibition of specific enzymes involved in nucleotide synthesis, preventing DNA replication and cell division.
Topoisomerase Inhibitors
- Topoisomerase I: Camptothecin analogs (irinotecan, topotecan)
- Topoisomerase II: Podophyllotoxins (etoposide, teniposide), anthracyclines (doxorubicin, daunorubicin)
- Mechanism: Inhibiting topoisomerases, preventing DNA replication, cell division, promoting strand breaks leading to DNA damage
- Clinical uses: Different types of cancers.
- Adverse Effects: Myelosuppression
Microtubule Inhibitors
- Vinca alkaloids (vincristine, vinblastine, vinorelbine)
- Mechanism: Disrupt microtubule function, blocking cell division
- Clinical uses: Lymphatic and solid tumors
- Adverse effects: Myelosuppression, peripheral neuropathy
- Taxanes (taxol, paclitaxel, docetaxel)
- Mechanism: Stabilize microtubules, blocking cell division
- Clinical uses: Advanced ovarian and breast cancer
- Adverse effects: Neutropenia, neurotoxicity, bradycardia, fluid retention, and hypersensitivity
PARP Inhibitors
- Olaparib
- Mechanism of action: Inhibits the PARP enzyme, preventing DNA repair in cancer cells with defective DNA repair mechanisms (e.g., BRCA mutations), leading to tumor cell death.
- Clinical uses: Cancers associated with damaged DNA repair pathways.
Hormone-Dependent Therapies
- Breast cancer (estrogen receptor-positive): Tamoxifen (SERM), fulvestrant (pure antagonist), anastrozole (Aromatase inhibitor)
- Breast and Prostate cancer: Leuprolide (GnRH analogue).
- Prostate cancer: Finasteride, Dutasteride (5-alpha-reductase inhibitors), bicalutamide (Antagonist of androgens receptors).
- Mechanisms of action: Interrupt hormone signaling pathways in hormone-dependent tumors, hindering tumor growth and reducing hormone dependence
Specific Tumor Pathways
- Inhibitors of tyrosine kinases, RAF kinases, and cyclin-dependent kinases
- Monoclonal antibodies (MAB) targeting specific tumor-associated proteins (e.g., rituximab, trastuzumab, ibrutinib)
Angiogenesis Inhibitors
- Bevacizumab, Vandetanib, Sunitinib, Sorafenib, Talidomide, Lenalidomide
- Mechanism of action: Inhibiting the growth of new blood vessels, hindering tumor growth and metastasis.
Immune System Activation
- Immune checkpoint inhibitors (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab)
- Cell therapy (e.g., T-cell therapies, CAR T-cell therapies)
- Vaccines
- Mechanisms of action: Reinforces the body's immune system to recognize and destroy cancer cells, potentially causing tumors to regress, or preventing them from growing or metastasizing.
Treatment Examples
- Non-Hodgkin Lymphomas: CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) + Rituximab
- Testis Cancer: BEP (bleomycin, etoposide, cisplatin) or PEI (cisplatin, etoposide, ifosfamide) regimens
Clinical Uses of Newer Anticancer Drugs
- Trastuzumab: breast cancer (HER2)
- Bevacizumab: metastatic colon cancer (VEGF)
- Rituximab: non-Hodgkin lymphoma (CD-20)
- Panitumumab: metastatic colon cancer (EGFR)
- Alemtuzumab: chronic lymphocytic leukemia (CD-52)
- Nivolumab: metastatic melanoma and non-small cell lung cancer (PD1)
- Atezolizumab: non-small cell lung cancer, renal cancer, and bladder cancer (PDL1)
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
This quiz covers essential concepts of antineoplastic drugs used in the treatment of cancer. It delves into the pathophysiology of cancer, including the role of DNA mutations in tumor genesis and the characteristics of cancer cells. Enhance your understanding of neoplasms and the crucial aspects of cancer treatment.
