Integrins are heterodimeric structural components of the plasma membrane whose 
ligands include a large number of extracellular matrix (ECM) proteins. The 
ligands contain Arg-Gly-Asp (RGD) sequences that enable recognition of ECM 
proteins by as many as eight integrins, but other distinguishing features of the 
proteins permit the integrins to generate intracellular signals specific to the 
ECM molecules. Recently, integrin αvβ3 has been shown to have a panel of 
previously unappreciated small molecule receptor sites for thyroid hormone and 
hormone analogues, for dihydrotestosterone, and for resveratrol, a polyphenol 
that has certain estrogen-like features. These binding sites are close to the 
RGD recognition site of αvβ3. The thyroid hormone receptor site on the 
extracellular domain of αvβ3 contains two domains with discrete functions in 
terms of intracellular protein trafficking and gene expression. Occupancy of the 
receptor by a deaminated thyroid hormone analogue, tetraiodothyroacetic acid 
(tetrac), prevents cell responses to agonist thyroid hormones (L-thyroxine; 3, 
5, 3'-triiodo-L-thyronine) and modulates expression of a number of cancer cell 
survival pathway genes in an up- or downregulation pattern coherent to induction 
of cell death. The small molecule thyroid hormone receptor on the integrin also 
regulates activity of five vascular growth factor receptors and/or their 
ligands, providing control of angiogenesis via specific pharmacologic regulation 
of this thyroid hormone receptor. The resveratrol receptor induces programmed 
cancer cell death via p53, even when the latter has undergone specific 
mutations. There is also evidence for the presence of several receptors on 
integrin αvβ3 for authentic steroids, including a dihydrotestosterone site that 
supports proliferation of breast cancer cells that lack nuclear androgen and 
estrogen receptors. The existence of these small molecule hormone receptors on 
an integrin with a remarkably complex functional profile defines novel 
pharmacologic options via individual small molecule receptor manipulation for 
control of cancer cell behavior. This refinement of up-down control at the level 
of discrete receptors is not a function of the use of αvβ3 antibody or RGD 
peptides that occlude regions of the integrin.