Pharmacological modulation of peptide growth factor receptor expression on tumor cells as a basis for cancer therapy.
Membrane receptors for peptide growth factor receptors (PGF-R) play a crucial role in the regulation of cancer cell proliferation and may behave as tumor associated antigens (TAA), which are currently regarded as specific targets for immunodetection and immunotherapy of human cancer. PGF-R are often more expressed by tumor cells than by normal counterparts and, by analogy to TAA, their surface expression may be regulated by cytokines. Moreover, the biological functions and specific ligands of most PGF-R are presently well elucidated as opposed to the great majority of TAA. PGF-R may, therefore, represent ideal cellular targets for at least two different therapeutic approaches: (i) naked or conjugated monoclonal antibodies and (ii) genetically engineered fusion proteins composed of PGF-R physiological ligands linked to genetically modified bacterial toxins. To date, clinical studies based on targeting of receptors for epidermal growth factor and interleukin-2 on tumor cells have been performed. Information from such studies suggests that PGF-R as well as TAA targeting strategies are clinically feasible, but that they still have to be optimized. A variety of host and tumor factors which affect targeting of neoplastic cells have been recently identified. For instance, it has been demonstrated that the antigenic density of the targeted molecule at the tumor cell surface is an important factor. In this view upregulation of PGF-R on cancer cells could be of major clinical advantage in immunotargeting. It has been reported that several cytokines and chemical compounds can induce PGF-R modulation on tumor cells. This paper reviews therapeutic opportunities related to the pharmacologic modulation of PGF-R expression. In addition a mechanistic hypothesis regarding PGF-R upregulation induced by cytostatic drugs and cytokines is proposed.
Tagliaferri
P
P
Cattedra di Oncologia Medica, Facoltà di Medicina, Università Federico II di Napoli, Italy.
Caraglia
M
M
Muraro
R
R
Pinto
A
A
Budillon
A
A
Zagonel
V
V
Bianco
A R
AR
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000502:physiology; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010455:Peptides / Q000276:immunology / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000187:drug effects* / Q000502:physiology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000922:Immunotoxins; D010455:Peptides; D017978:Receptors, Growth Factor