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Provided here is a comprehensive examination of the basic and
clinical condition of three innovative and promising approaches to
cancer therapy, which may support or even substitute chemotherapy:
differentiation, immunomodulation, and inhibition of angiogenesis.
Differentiation shouldnormalize neoplastic cells and make them
compatible with the host. Its feasibility with retinoids,
interferons, chemotherapeutic and other agents is discussed.
Modulation by biological agents, cytotoxic effector cells and drugs
is considered in attempts to boost endogenous antitumour defenses
and/or to render neoplastic cells more susceptible to the immune
attack of the host. Finally, the important aspect of interfering
with tumour blood vessel development and function is taken into
account. Consideringthe importance that chemotherapy has in cancer
treatment and in view of a more and more integrated strategy, the
relationship between the aforementioned approaches and
chemotherapeutic agents and chemoresistance is treated in detail.
The addition of chemotherapy as an effective means to treat cancer
has had a major impact on selected human malignancies. Due to a
general inability to dif ferentiate between normal and neoplastic
cells, little selectivity exists in currently used oncolytic drugs.
Consequently, significant toxicity to the patient is expected when
systemic cancer chemotherapy is chosen as an appropriate
therapeutic in tervention. Much of this toxicity, such as damage to
the bone marrow, gastroin testinal tract, or hair follicles, is
predictable based upon the fact that anticancer drugs kill actively
dividing cells. These types of toxicities, while serious, are
usually manageable and reversible and are, therefore, not often
considered to be dose limiting. Unfortunately, several of the most
important anticancer drugs also damage tissues in which the growth
fraction is relatively small. Such toxicities can not be predicted
based on the chemical structure of the drugs, are often not
detected in preclinical studies, and are encountered frequently for
the first time in clinical studies. Further, unlike most of the
proliferative-dependent toxicities, the unpre dicted toxicities are
usually irreversible or only partially reversible upon cessation of
drug administration. Because of this, the unpredicted toxicities
are referred to as dose limiting. They represent a significant
barrier to the ultimate efficacy of several of our most important
anticancer drugs.
The addition of chemotherapy as an effective means to treat cancer
has had a major impact on selected human malignancies. Due to a
general inability to dif ferentiate between normal and neoplastic
cells, little selectivity exists in currently used oncolytic drugs.
Consequently, significant toxicity to the patient is expected when
systemic cancer chemotherapy is chosen as an appropriate
therapeutic in tervention. Much of this toxicity, such as damage to
the bone marrow, gastroin testinal tract, or hair follicles, is
predictable based upon the fact that anticancer drugs kill actively
dividing cells. These types of toxicities, while serious, are
usually manageable and reversible and are, therefore, not often
considered to be dose limiting. Unfortunately, several of the most
important anticancer drugs also damage tissues in which the growth
fraction is relatively small. Such toxicities can not be predicted
based on the chemical structure of the drugs, are often not
detected in preclinical studies, and are encountered frequently for
the first time in clinical studies. Further, unlike most of the
proliferative-dependent toxicities, the unpre dicted toxicities are
usually irreversible or only partially reversible upon cessation of
drug administration. Because of this, the unpredicted toxicities
are referred to as dose limiting. They represent a significant
barrier to the ultimate efficacy of several of our most important
anticancer drugs."
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