blocks as the host that it is destroying. Therefore, a tumor is “self acting as nonself.”
Drugs engineered to attack tumor nucleic acid targets will correspondingly also target
(in principle) all other cells within the host’s body. This introduces immense complex-
ities when endeavoring to design cancer chemotherapeutic agents with optimal cancer-
killing efficacy but minimal toxicity. Since the toxicities are primarily mediated by the
therapeutic mechanism of action, separation of pharmacophore from toxicophore
becomes a seemingly insurmountable problem. Also, tumors show varying sensitivities
to the anticancer therapies that are available (see table 7.1).
The most reasonable approach for addressing this dilemma is to exploit differences
in cell growth kinetics between cancer cells and host cells. A hallmark of cancerous cell
growth is the rapidity of its cellular proliferation. At any given time, a malignant tumor
should have more cells undergoing mitosis and replication than other tissues in the host.
462 MEDICINAL CHEMISTRY
Table 7.1 Varying Responsiveness of Tumors to Anticancer Drugs
Tumor Treatment
Chemoresistant tumors—not responsive to chemotherapy
Adrenocortical carcinoma Combination chemotherapy
Gliomas (brain) Surgery
Hypernephroma (kidney) Surgery, chemotherapy, immunotherapy
Malignant melanoma (skin) Surgery
Pancreatic adenocarcinoma Surgery
Pancreatic islet cell carcinoma Surgery, combination chemotherapy
Squamous cell bronchogenic carcinoma (lung) Surgery and radiotherapy ± chemotherapy
Moderately chemosensitive
Bladder carcinoma Combination chemotherapy (local and systemic)
Breast carcinoma Surgery, radiotherapy, chemotherapy
Bronchogenic carcinoma (lung) Combination chemotherapy
Endometrial carcinoma (uterus) Hormonal and cytotoxic chemotherapy, surgery
Head and neck carcinomas Chemotherapy and surgery/radiotherapy
Multiple myeloma (bone marrow) Combination chemotherapy
Ovarian carcinoma Combination chemotherapy, surgery
Prostate carcinoma Hormonal therapies
Chemosensitive—Tumors responsive to chemotherapy
Acute leukemias Combination chemotherapy
Burkitt’s lymphoma Surgery, radiotherapy, chemotherapy
Choriocarcinoma Methotrexate, dactinomycin
Hodgkin’s lymphoma Combination chemotherapy, radiotherapy
Non-Hodgkin’s lymphoma Combination chemotherapy, radiotherapy
Retinoblastoma (eye) Radiotherapy, cyclophosphamide
Rhabdomyosarcoma (muscle) Cyclophosphamide
Testicular carcinoma Surgery, radiotherapy, chemotherapy
Wilms’ tumor (children) Surgery, radiotherapy, chemotherapy
(Adapted from D. G. Grahame-Smith, J. K. Aronson (2002). Clinical Pharmacology and Drug Therapy, 3rd
Edn. New York: Oxford University Press. With permission.)