Drug Targeting Organ-Specific Strategies

8.2.2 Histogenesis
The traditional principle of tumour histogenesis is that neoplasms characterized by a certain
phenotype arise from normal cells of similar phenotype. Considerable evidence has accumulated
in recent years which indicates that this histogenetic assumption is incorrect. Most, if
not all, neoplasms arise from immature cells, which in the course of neoplastic transformation
acquire phenotypic features equivalent to those of one or more normal cell types. Often this
differentiation develops along lines analogous to those expected under normal conditions for
that particular cell.
The characterization and genesis of neoplasms on the basis of morphological (shape-related)
features is needed for the evaluation of the common traits and differences among the
many types of neoplasms that can affect the human body. Such identification and classification
confirms that many different cell types can be involved in cancer.
The traditional classification of neoplasms on the basis of their behaviour postulates benign
(non-metastatic) and malignant (metastatic) types. These designations are determined
by the expected behaviour of the tumour rather than its microscopic appearance. This division
of tumours into benign and malignant represents a gross oversimplification of the wide
behavioural range exhibited by tumour cells in terms of local aggressiveness and metastatic
potential.
Determination of the microscopic type of a malignancy does not always provide all the information
needed to predict the clinical course of the disease or to choose the appropriate
therapy. Microscopic grading is an attempt to determine the degree of malignancy independently
from cell type and is based on the evaluation of several parameters, which vary depending
on the system being studied. They include cellularity, pleomorphism, mitotic activity,
type of margins, amount of matrix formation, and presence of haemorrhage, necrosis and
inflammation.
The number of grades varies from system to system, but in general the three-grade system
(well differentiated, moderately differentiated, and poorly differentiated, or undifferentiated;
or grades I, II and III, respectively) has proved to be the most reproducible and the best
suited to prediction of survival.
For more detailed information about cancer pathology readers are referred to De Vita
et al. [7].
8.3 Currently Available Therapeutics
8.3 Currently Available Therapeutics 201
Non-surgical methods of cancer treatment, primarily radiation therapy and chemotherapy,
rely almost exclusively on procedures that kill cells.The main problem with these treatments
is that they do not provide specificity for cancer cells. In the case of radiation therapy, a degree
of specificity is achieved by localizing the radiation to the tumour and its immediate surrounding
normal tissue. For anti-cancer drugs, it is primarily the rapid proliferation of many
of the cancer cells that makes them more sensitive to cell killing than their normal counterparts.
However, both modalities are limited by their cytotoxic effects on normal cells. In the
case of radiotherapy, normal tissue surrounding the tumour limits the radiation dose, where-