MedOrg - Antineoplastic Agents (Alkylating Agents)
1. Classes of Antineoplastics: alkylating agents, antibiotics, natural products, antimetabolites, and tyrosine kinase
inhibitors.
2. Antineoplastic Agents: cancer treatment, with focus on their chemistry, usage, metabolism, and adverse effects.
3. Antineoplastics emphasize on ___________: cell division and cell death regulation, and how drugs influence these
processes.
4. Antineoplastics also highlights __________________: how cancer cells develop resistance 5. Key biological topics
discussed:: Apoptosis (programmed cell death) DNA alkylation
Reactive oxygen species (ROS)
Growth factors in transcription and translation
6. mechanisms beyond cancer Pharmacists should understand: Neurodegenerative diseases Mutagenicity
Cardiovascular toxicity
Cell signaling
7. Cancer: Defined by the American Cancer Society as uncontrolled growth and spread of abnormal cells, potentially fatal if
untreated.
8. Neoplasia: uncontrolled growth of new tissue forming tumors (malignant or benign)
9. Tumor Types:: Malignant tumors
Benign tumors
10. Malignant tumors: (Type of tumor) invade nearby tissues and can metastasize (spread to distant parts).
11. Benign tumors: (type of tumor) do not invade or metastasize 12. Cancer Treatment Approaches:: Primary treatment:
Supplementary treatments:
Chemotherapy: .
13. Primary treatment: surgery.
14. Supplementary treatments:: radiation and chemotherapy (surgery is not enough or feasible.)
15. Chemotherapy:: cell killing drugs (including antibiotics and anticancer agents).
16. Challenges in Chemotherapy:: selective toxicity rapidly dividing cells
17. selective toxicity: hard to achieve since cancer cells use many of the same pathways as normal cells.
18. targets rapidly dividing cells: not all cancer cells proliferate quickly, and some normal tissues also divide rapidly
19. Advancements in Therapy:: Newer drugs (e.g., monoclonal antibodies , TK inhibitors) target specific growth factor
pathways.
20. Newer drugs (e.g., monoclonal antibodies , TK inhibitors): used in combination with traditional therapies for improved
outcomes
,21. Importance of Early Detection: more effective treatment and higher 5 year survival rates.
22. Improved diagnostics and public awareness: help detect cancers earlier.
23. Cancer Staging:: TNM systemÏ
ÏStage 0-IV system
24. TNM system: T = Tumor size,Ë
ËN = Lymph node involvement,
ËM = Metastasis (0 = no, 1 = yes).
25. Stage 0-IV system: Higher numbers indicate more advanced disease;
26. Stage IV: metastasis
27. Pancreatic Cancer: 5 year survival increased from 2% (1975-77) to 5% (1996-2003).
28. Lung Cancer: 5 year survival rose from 13% to 16% (1975-77) & (1996-2003).
29. some improvement are due to ______: earlier detection rather than more effective treatment
30. Organ of Origin: Traditional cancer class.; misleading
31. Cancers in the same organ may have ______________: different genetic causes 32. Drug response: partly depends on
genetic abnormalities within the cells.
33. Primary Risk Factor: Age
34. environmental toxins: Other cancer risk
35. Cancer risk increases with age due to ____________________: cumulative DNA mutations during cell divisions.
36. Normal cell proliferation is triggered by _______________: external mitogenic signals (e.g., hormones, growth factors).
37 Cancer cells may:: Produce their own growth factors (autocrine signaling).Ë ËNo longer
require growth factors to proliferate.
ËHave permanently activated signal transduction pathways leading to constant division.
38. Oncogenes: mutated forms of proto oncogenes that drive cancer growth
39. Proto oncogenes: normal genes that regulate growth; mutations or DNA translocations convert them into oncogenes.
40. Oncogene activation: varies among patients with the same type of cancer.
, 41. Cell Cycle phases: G1 phase: Ï ÏG0 phase:
ÏS phase:
ÏG2 phase:
ÏM phase:
42. G1 phase:: synthesis of enzymes for DNA replication.
43. G0 phase: resting/non dividing state; reversible.
44. S phase: DNA replication
45. G2 phase:: protein synthesis and microtubule formation
46. M phase: mitosis (prophase telophase) and cell division.’
47. Cyclins and CDKs: regulate progression through the cycle
48. G1: Cyclin D/CDK4/6
49. G1 to S.: Cyclin E/CDK2
50. G2 and M transitions: Cyclins A & B with CDKs
51. Cell Cycle: tightly regulated to ensure proper division and genome integrity.
52. Key tumor suppressor proteins: p53:Ë
ËRb and p21Cip1
53. p53: transcription factor that activates DNA repair or apoptosis in case of severe damage ("guardian of the cell").
54. Rb and p21Cip1: also regulate cycle checkpoints.
55. p53 dysfunction: common in many cancers, allowing damaged cells to survive and mutate further.
56. Apoptosis Pathways: Intrinsic and Extrinsic
57. Intrinsic Pathway: Triggered by mitochondrial release of cytochrome 58. Intrinsic Pathway: Regulated by:
i. Pro apoptotic proteins: Bad, Bax, Bid.
ii. Anti apoptotic proteins: Bcl 2, Bcl XL.
1. Classes of Antineoplastics: alkylating agents, antibiotics, natural products, antimetabolites, and tyrosine kinase
inhibitors.
2. Antineoplastic Agents: cancer treatment, with focus on their chemistry, usage, metabolism, and adverse effects.
3. Antineoplastics emphasize on ___________: cell division and cell death regulation, and how drugs influence these
processes.
4. Antineoplastics also highlights __________________: how cancer cells develop resistance 5. Key biological topics
discussed:: Apoptosis (programmed cell death) DNA alkylation
Reactive oxygen species (ROS)
Growth factors in transcription and translation
6. mechanisms beyond cancer Pharmacists should understand: Neurodegenerative diseases Mutagenicity
Cardiovascular toxicity
Cell signaling
7. Cancer: Defined by the American Cancer Society as uncontrolled growth and spread of abnormal cells, potentially fatal if
untreated.
8. Neoplasia: uncontrolled growth of new tissue forming tumors (malignant or benign)
9. Tumor Types:: Malignant tumors
Benign tumors
10. Malignant tumors: (Type of tumor) invade nearby tissues and can metastasize (spread to distant parts).
11. Benign tumors: (type of tumor) do not invade or metastasize 12. Cancer Treatment Approaches:: Primary treatment:
Supplementary treatments:
Chemotherapy: .
13. Primary treatment: surgery.
14. Supplementary treatments:: radiation and chemotherapy (surgery is not enough or feasible.)
15. Chemotherapy:: cell killing drugs (including antibiotics and anticancer agents).
16. Challenges in Chemotherapy:: selective toxicity rapidly dividing cells
17. selective toxicity: hard to achieve since cancer cells use many of the same pathways as normal cells.
18. targets rapidly dividing cells: not all cancer cells proliferate quickly, and some normal tissues also divide rapidly
19. Advancements in Therapy:: Newer drugs (e.g., monoclonal antibodies , TK inhibitors) target specific growth factor
pathways.
20. Newer drugs (e.g., monoclonal antibodies , TK inhibitors): used in combination with traditional therapies for improved
outcomes
,21. Importance of Early Detection: more effective treatment and higher 5 year survival rates.
22. Improved diagnostics and public awareness: help detect cancers earlier.
23. Cancer Staging:: TNM systemÏ
ÏStage 0-IV system
24. TNM system: T = Tumor size,Ë
ËN = Lymph node involvement,
ËM = Metastasis (0 = no, 1 = yes).
25. Stage 0-IV system: Higher numbers indicate more advanced disease;
26. Stage IV: metastasis
27. Pancreatic Cancer: 5 year survival increased from 2% (1975-77) to 5% (1996-2003).
28. Lung Cancer: 5 year survival rose from 13% to 16% (1975-77) & (1996-2003).
29. some improvement are due to ______: earlier detection rather than more effective treatment
30. Organ of Origin: Traditional cancer class.; misleading
31. Cancers in the same organ may have ______________: different genetic causes 32. Drug response: partly depends on
genetic abnormalities within the cells.
33. Primary Risk Factor: Age
34. environmental toxins: Other cancer risk
35. Cancer risk increases with age due to ____________________: cumulative DNA mutations during cell divisions.
36. Normal cell proliferation is triggered by _______________: external mitogenic signals (e.g., hormones, growth factors).
37 Cancer cells may:: Produce their own growth factors (autocrine signaling).Ë ËNo longer
require growth factors to proliferate.
ËHave permanently activated signal transduction pathways leading to constant division.
38. Oncogenes: mutated forms of proto oncogenes that drive cancer growth
39. Proto oncogenes: normal genes that regulate growth; mutations or DNA translocations convert them into oncogenes.
40. Oncogene activation: varies among patients with the same type of cancer.
, 41. Cell Cycle phases: G1 phase: Ï ÏG0 phase:
ÏS phase:
ÏG2 phase:
ÏM phase:
42. G1 phase:: synthesis of enzymes for DNA replication.
43. G0 phase: resting/non dividing state; reversible.
44. S phase: DNA replication
45. G2 phase:: protein synthesis and microtubule formation
46. M phase: mitosis (prophase telophase) and cell division.’
47. Cyclins and CDKs: regulate progression through the cycle
48. G1: Cyclin D/CDK4/6
49. G1 to S.: Cyclin E/CDK2
50. G2 and M transitions: Cyclins A & B with CDKs
51. Cell Cycle: tightly regulated to ensure proper division and genome integrity.
52. Key tumor suppressor proteins: p53:Ë
ËRb and p21Cip1
53. p53: transcription factor that activates DNA repair or apoptosis in case of severe damage ("guardian of the cell").
54. Rb and p21Cip1: also regulate cycle checkpoints.
55. p53 dysfunction: common in many cancers, allowing damaged cells to survive and mutate further.
56. Apoptosis Pathways: Intrinsic and Extrinsic
57. Intrinsic Pathway: Triggered by mitochondrial release of cytochrome 58. Intrinsic Pathway: Regulated by:
i. Pro apoptotic proteins: Bad, Bax, Bid.
ii. Anti apoptotic proteins: Bcl 2, Bcl XL.
