COMBINED THERAPY hdhhslshsalhlahuuue.pptx

for oncology

1. COMBINED THERAPY: CHEMOTHERAPY, ENDOCRINE THERAPY AND BIOLOGICAL AGENTS PRESENT BY Fazila Malengera SUPERVISOR: Dr RICHARD komakech Dr ISRAEL Luutu

2. OUTLINE PREREQUISITES: Cell cycle Regulation of cell cycle CHEMOTHERAPY AGENT PRINCIPELS OF HORMONOTHERAPY PRINCIPLES OF BIOLOGICAL AGENT PRINCIPELS OF CANCER TRAITEMENT COMBINATION

3. DEFINITION a cell is the fundamental, self-contained unit of life. It's the smallest structure capable of carrying out all the basic functions of living organisms The cell cycle is a fundamental process for growth, development, and repair in multicellular organisms.  A cell cycle is a series of events that takes place in a cell as it grows and divides. A cell spends most of its time in what is called interphase, and during this time it grows, replicates its chromosomes, and prepares for cell division. The cell then leaves interphase, undergoes mitosis, and completes its division.

4. CELL CYCLE

5. CONT…

6. REGULATION OF CELL CYCLE The G1/S checkpoint is activated in G1 cells to inhibit S-phase entry. The intra-S checkpoint is activated in S-phase cells to prevent the not-yet-activated origins from initiating  DNA replication . The G2/M checkpoint is activated in G2 cells to inhibit the entry into mitosis. The  cell cycle checkpoints  are triggered by  protein phosphorylation  that is readily reversible upon  protein dephosphorylation  so that  cell cycle progression  can resume after DNA lesions are repaired

7. CELL CYCLE CHECK POINT

8. I. CHEMOTHERAPY  a drug treatment that uses powerful chemicals to destroy cancer cells or slow their growth Cancer, at the cellular level, is characterized by the uncontrolled growth and division of abnormal cells . 2 TYPES: cell cycle depend and non cell cycle depend

9. MECANISM OF ACTION

10. Cytotoxic agent Alkylating Agents Antimetabolites Antitubulins Topoisomerase II inhibitors Topoisomerase I inhibitors Antibiotics Miscellaneous

11. II. HORMONE THERAPY Hormone therapy in cancer management is based on the principle that certain tumors depend on hormones for growth and survival . By blocking, lowering, or altering these hormones—or their receptors—we can slow or stop tumor progression.

12. MECANISM OF ACTION A. Hormone suppression (reduce production ) Surgical ablation: Oophorectomy (removing ovaries in premenopausal women) Orchiectomy (removing testes in men with prostate cancer) Medical suppression: LHRH (GnRH) agonists/antagonists → suppress gonadal hormone production Adrenal enzyme inhibitors (e.g., ketoconazole, abiraterone) B. Hormone receptor blockade Anti-estrogens (e.g., tamoxifen, fulvestrant ) → block estrogen receptors in breast tissue. Anti-androgens (e.g., bicalutamide, enzalutamide) → block androgen receptors in prostate cells.

13. CONT.. C. Hormone antagonism Drugs compete with natural hormones for binding sites → prevent activation. D. Hormone supplementation (less common) In some cases, high doses of certain hormones (e.g., progestins in endometrial cancer) can have an anti-tumor effect by counteracting other hormone pathways.

14. WHEN DOES THIS WORK 1. Tumor must be hormone-sensitive Test for hormone receptor status (e.g., ER, PR in breast cancer; AR in prostate cancer). 2. Stage & timing Can be used as primary therapy, adjuvant therapy, or for palliation in advanced disease. 3. Reversibility & chronic use Medical suppression is reversible; surgical ablation is permanent. 4. Selectivity & toxicity Aim for maximum tumor effect with minimal systemic side effects.

15. Examples for hormonal therapy Breast cancer: Tamoxifen, aromatase inhibitors, ovarian suppression. Prostate cancer: LHRH analogs, anti-androgens, abiraterone. Endometrial cancer: Progestins. Thyroid cancer: Thyroid hormone suppression therapy to lower TSH.

16. III. BIOLOGICAL AGENTS These therapies are currently being developed by modifying bispecific antibodies and CAR T cells to improve their efficiency and bioavailability. Biological agents, also known as  biologics , work by harnessing the body's immune system to fight cancer or by directly targeting specific molecules involved in cancer cell growth and survival. They differ from traditional chemotherapy by targeting cancer cells in a more specific manner, often with fewer off-target effects

17. MECANISM OF ACTION 1. Immune System Modulation: Monoclonal Antibodies :  These antibodies bind to specific proteins on cancer cells, marking them for destruction by the immune system or blocking their growth signals.  Cytokines :  These signaling molecules, like interleukins and interferons, stimulate immune cells to attack cancer cells.  Cancer Vaccines :  These vaccines help the immune system recognize and target cancer cells, prompting a targeted immune response. 

18. 2. Targeting Cancer Cell Growth and Survival: Tyrosine Kinase Inhibitors :  These drugs block specific enzymes (tyrosine kinases) that promote cancer cell growth and division.  Angiogenesis Inhibitors :  These agents prevent the formation of new blood vessels that tumors need to grow and spread, cutting off their nutrient supply.  Signal Transduction Inhibitors :  These drugs interfere with the signaling pathways that control cell growth, division, and survival.  Gene Therapy :  This approach modifies genes within cancer cells to make them more susceptible to treatment or to trigger an immune response. 

19. 3. Directly Targeting Cancer Cells: Phytochemicals :  Natural compounds found in plants can interfere with various signaling pathways and protein kinases, impacting cancer cell growth, metabolism, and even their sensitivity to other drugs.  Oncolytic Viruses :  These viruses are engineered to selectively infect and kill cancer cells, while leaving healthy cells unharmed. 

20. PRINCIPLES OF CANCER TRAITEMENT revolve around achieving either a cure ( curative treatment ) or improving quality of life ( palliative treatment ).  Treatments are often individualized and may involve surgery, radiation therapy, chemotherapy, hormone therapy, targeted therapy, and/or immunotherapy.  A well-conceived plan should consider the patient's overall health, potential side effects, and the need to address metastases and paraneoplastic syndromes

21. GAOLS Curative Treatment:  Aims to eradicate the cancer with the goal of long-term survival or cure. Palliative Treatment:  Focuses on managing symptoms, improving quality of life, and extending life when a cure is not possible. 

22. MODALITIES Surgery :  Removal of the tumor and potentially surrounding tissue.  Radiation Therapy :  Using high-energy rays to kill cancer cells.  Chemotherapy :  Using drugs to kill or slow the growth of cancer cells.  Hormone Therapy :  Blocking or replacing hormones to slow cancer growth.  Targeted Therapy :  Using drugs that target specific molecules involved in cancer cell growth.  Immunotherapy :  Using the body's immune system to fight cancer. 

23. APPROACH  Individualized Approach : Each patient's treatment plan should be tailored to their specific type and stage of cancer, overall health, and other factors.  Consideration should be given to the potential benefits and risks of each treatment option.    Importance of Timing and Sequencing :  Minimizing Toxicity:  Addressing Metastasis and Paraneoplastic Syndromes:

24. COMBINATION Cancer medications are most effective when given in combination . The rationale for combination therapy is to use medications that work by different mechanisms , thereby decreasing the likelihood that resistant cancer cells will develop. When medications with different effects are combined, each medication can be used at its optimal dose, without intolerable side effects.

25. Rationale for Combination A. Different Mechanisms of Action Chemotherapy: Non-specific cytotoxic effect → kills rapidly dividing cells (both cancerous and some normal). Biological agents: Target specific molecules or immune pathways that cancer cells rely on for growth and survival. Hormonal therapy: Cuts off or blocks hormone-driven growth signals in hormone-sensitive tumors. Result: Multiple “fronts” of attack → higher likelihood of killing cancer cells and preventing regrowth. B. Overcoming Resistance Cancer cells can adapt to one therapy (e.g., develop resistance to hormonal therapy alone). Adding chemotherapy or a targeted biological agent hits alternative pathways → limits escape mechanisms. C. Synergistic Effects Some biological agents sensitize cancer cells to chemotherapy (e.g., trastuzumab with paclitaxel in HER2+ breast cancer). D

26. Principles for Safe and Effective Combination Patient selection → Molecular testing for biological agent targets; receptor testing for hormonal therapy. Timing → May be given concurrently or sequentially depending on tumor type and toxicity profile. Toxicity management → Each class has different side effects, so careful monitoring is needed to avoid additive toxicity. Resul t: Multiple “fronts” of attack → higher likelihood of killing cancer cells and preventing regrowth. Overcoming Resistance

27. Safe and Effective Combination Patient selection → Molecular testing for biological agent targets; receptor testing for hormonal therapy. Timing → May be given concurrently or sequentially depending on tumor type and toxicity profile. Toxicity management → Each class has different side effects, so careful monitoring is needed to avoid additive toxicity.

28. REFERENCES Oncology, principles of cancer traitment Notional cancer institute, dictionary of cancer term