CANCER CHEMOTHERAPY

CANCER CHEMOTHERAPY
By:Dr. Debra Laskin
Rutgers.edu

Cancer (Neoplastic Disease)
Types of Cancers
Hematologic Malignancies
Leukemias
Lymphomas
Hodgkin’s Disease
Non-Hodgkin’s Lymphoma
Solid Tumors
Carcinomas
Sarcomas
Hematologic Malignancies
Tumors of blood forming organs and cells
* Leukemias: Proliferation of immature progenitors which circulate in blood
o Acute lymphocytic leukemia (ALL, BM lymphblasts)
o Chronic lymphocytic leukemia (CLL- immature B cells)
o Acute myelocytic leukemia (AML, BM myeloid cells)
o Chronic myelocytic leukemia (CML, myeloid cells; Philadelphia chromosome)
* Lymphomas: Lymph System
o Hodgkin’s Disease: lymph nodes
o Non-Hodgkin’s lymphoma: lymphocytes (CLL)
Solid Tumors
Can occur in any organ or tissue; malignant (metastatic and invasive)
* Carcinomas: Arises from epithelial cells; malignant by definition
* Sarcomas: Cancer of connective or supportive tissue (bone, cartilage, fat, muscle, blood vessels) and soft tissue

Cancer Chemotherapy Versus Antimicrobial Chemotherapy
I. Goal
II. Selective Toxicity
III. Immune System
IV. Kinetics of killing

Goal
* ACT: Get rid of invading organisms, restore health
* CCT: Kill as many tumors cells as possible without killing too many normal cells; tumor regression, increased patient survival time, alleviation of symptoms

Selective Toxicity
* ACT: Exploit biochemical differences between pathogenic organism and host; selective toxicity
* CCT: Only quantitative differences between normal and neoplastic cells; differences in growth rate, treatment is nonselective

Immune System
Kinetics
Tumor Cell Killing: First Order Kinetics
Tumor burden
Time
Stationary phase
New steady state
Determinants of Responsiveness to Cancer Chemotherapy
Tumor Determinants of Responsiveness
Total Tumor Burden (Size)
Cell Cycle
Cell Cycle Phase
Phases of Cell Cycle
Cancer Chemotherapy
Cell Cycle Specific Agents (self limiting)
Cell Cycle Nonspecific Agents
Drug Resistance
Mechanisms vary with drug
Host Determinants
General health status of patients
Immune status
General Considerations Cancer Chemotherapy
Adjuvant Therapy
Drug Toxicity
Most CCT agents:
Cytotoxic agents- kill all rapidly growing cells, nonselective
Side Effects of Anticancer Drugs
Cancer Chemotherapeutic Agents
Alkylating Agents
Mechanism of Action
Evidence in mammalian cells
Bi-functional: more toxic can cross link DNA
Resistance: excision/DNA repair enzymes; get rid of alkylated DNA
Cell cycle nonspecific
Classes of Alkylating Agents
Nitrogen Mustards
Classes of Alkylating Agents
Nitrosoureas
Classes of Alkylating Agents
Methane sulfonate esters (Alkyl sulfonates)
Folic Acid Analogs-Antifolates
Mechanism of Action
Cytotoxic Effects of Inhibiting DHFR
Leucovorin Rescue
Combination chemotherapy
Adjuvant to surgery
Antimetabolites
DNA Synthesis
Salvage Pathways
Purine Analogs
Mechanisms of Cytotoxicity
Resistance
Lethal Synthesis
Irreversible Ic
5-Fluorouracil
Mechanism of Action
Microtuble Inhibitors: Taxanes
Chromatin Function Inhibitors
Chromatin Function Inhibitors
Antibiotics
Steroid Hormones
Estrogens and Androgens
Immunotherapy: Monoclonal Antibodies
Monoclonal Antibodies
Targeted Therapy
Traditional CCT
Drugs inhibit proliferation

CANCER CHEMOTHERAPY