Medicinal Chemistry

(Jacob Rumans) #1

of malignancy in a neoplasm. Likewise, metastasis also unequivocally marks a tumor as
malignant, since benign neoplasms cannot metastasize. Decreased cohesiveness of indi-
vidual cells within the tumor mass facilitates metastasis by enabling individual cells to
readily leave their site of origin and to be transplanted to other sites. Loss of contact inhi-
bition enables malignant cells, either from the site of primary origin or from any secondary
metastatic site, to grow in an erosive fashion, progressively impinging upon and ultimately
destroying contiguous normal cells and tissues.
Neoplasms can be broadly categorized as either “simple” or “compound”; simple
neoplasms are composed of one single neoplastic cell type, whereas compound neoplasms
contain more than one neoplastic cell type. Both simple and compound neoplasms may be
either benign or malignant. There are two types of malignant simple neoplasms: carcino-
mas and sarcomas. A carcinoma is a malignant neoplasm that is derived from an epithe-
lial cell line. Epithelium is the cellular layer covering all inner and outer free surfaces
(cutaneous, serous, or mucous) within the body, including the skin, gastrointestinal tract,
genitourinary tract, respiratory tract, and the associated glands and structures derived
therefrom. The type of carcinoma reflects the organ of origin: skin (squamous cell car-
cinoma), hair follicle (basal cell carcinoma), respiratory tract (bronchogenic carcinoma),
urinary bladder (transitional cell carcinoma). When the carcinoma arises from the epithe-
lium that lines a gland, then the resulting neoplasm is called an adenocarcinoma. Thus,
a malignant tumor arising from a gland lining the large intestine would be an adenocar-
cinoma of the colon. Since mammary glands are embryologically derived from modified
sweat glands, breast cancer tumors are carcinomas.
A malignant sarcoma is a neoplasm derived from a mesenchymal cell line. Mesenchyme
is that portion of the body that produces the muscles, connective tissues (e.g., tendons,
cartilage, bone, fat), fluid distribution systems (i.e., blood and lymph vessels), and blood
cells (e.g., erythrocytes [red blood cells], leukocytes [white blood cells: granulocytes,
monocytes]). The type of sarcoma reflects the organ of origin: fat (liposarcoma), bone
(osteogenic sarcoma), lymph vessel (lympangiosarcoma), muscle (rhabdomyosarcoma),
blood cell (leukemia). The malignancies of blood cells (leukemias, multiple myeloma)
do not produce the localized tumor masses typically associated with neoplasms. From
a biological perspective, sarcomas are distinct and different from carcinomas.
Collectively, carcinomas and sarcomas are much more frequent than the rather
uncommon compound neoplasms that are populated by more than one neoplastic cell line.
Compound tumors are frequently derived from “uncommitted cells” which aretotipotential
orpluripotential, i.e., capable of differentiating into a variety of different cell types.
Accordingly, compound neoplasms characteristically develop within embryonic cells
(primitive cell “rests,” sequestered and left over after the person’s embryogenetic devel-
opment) or cells in gonads (reproductive cells waiting to pass their full complement of
genetic information to an offspring). A common type of benign compound neoplasm is
theteratoma, which is principally encountered in the gonads; a single teratoma tumor
may contain many types of tissue resembling fat, skin, teeth, hair follicles, gut epithelium,
or muscle. One or more of these individual cell lines within a compound neoplasm can
become malignant. A skin-type epithelial cell within a teratoma could therefore become
malignant, producing a squamous cell carcinoma within a teratoma and thus producing
a tumor referred to as a teratocarcinoma.
Clinically, the signs and symptoms of cancer are as varied and diverse as the types of
neoplasm. If the site of origin of the neoplasm (primary tumor) is in an easily observed


460 MEDICINAL CHEMISTRY

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