Chemotherapyvs.

Targeted Therapy

James J Lechner, MD

Medical DirectorProvidence Regional Cancer System

The Role of Systemic Therapy

• Treatment of the whole body• Intent?

– Induction therapy– Adjuvant therapy– Palliative

Chemotherapy vs Targeted Therapy

• Chemotherapy:– Drugs that effect cells that are doubling– Not very specific– Mostly intravenous, some oral agents– Cytotoxic

• Targeted therapy:– Drugs that inhibit a more specific target in cells– Many are oral agents– Mixture of cytostatic and cytotoxic

Sidney Farber (1903–1973)

The Normal Cell Cycle

Classes of Chemotherapy Drugs

• Alkylating agents• Antimetabolites• Anthracyclines• Anti-tumor antibiotics• Plant alkaloids

– Topoisomerase inhibitors– Vinca alkaloids– Taxanes

Class Example Method of Action Cycle Specfic

Alkylating agents Cytoxan Effects DNA chemically All

Antimetabolites 5-FUGemzar

Substitutes for normal cell building blocks

S

Anthracyclines Adriamycin DNA damage or inhibit topoisomerase

All

Anti-tumor Antibiotics

Bleomycin DNA damage All

Topoisomerase Inhibitors

Irinotecan Complex DNA and topoisomerase together

SG-2

Vinca Alkaloids Vincristine Binds to tubulin, interferes with mitosis

M

Taxanes TaxolTaxotere

Prevents microtubules from disassociating

M

Targeted Therapy

Attempts to take advantage of a genetic change in the malignant cells

The Origins of CML

Gleevec

BRAF Mutation in Melanoma

EML4-ALK Mutation in Lung Cancer

• Present in 3-5% of non-small cell lung cancer, usually adenocarcinoma

• Mutation leads to formation of a fusion gene that codes for an abnormal tyrosine kinase receptor

Response to crizotinib in patients with EML-ALK NSCLCA

Drugs in the Pipeline for ALK

Her-2/neu

• About 25% of breast cancer cases are associated with a amplification of the genes coding for a cell surface receptor called Her-2/neu

• These cells may a 1000 fold increase in the number of these receptors over normal breast cells

• Associated with rapid growth

Herceptin

There Are Multiple Agents Already Available

Non-Hodgkin Lymphoma

Old News Targeted Therapy

(But crucial in breast cancer)

Normal Estrogen Effects in Breast Cells

Anti-estrogen Therapy in Breast Cancer

Antibody-Drug Conjugates

A New Agent in Hodgkin's Disease

Stimulating an Immune Response

New Agent in Melanoma Therapy

Pushing Immune Cells to Recognize Cancer Cells

Provenge in Prostate Cancer

Recommended Reading

Thank You