257Dendrimers are a novel class of 3D nanoscale, core-shell structures that can be
precisely synthesized for a wide range of applications including oncology.
Specialized chemistry techniques enable precise control over the physical and
chemical properties of the dendrimers. They are most useful in drug delivery but can
also be used for the development of new pharmaceuticals with novel activities.
Polyvalent dendrimers interact simultaneously with multiple drug targets. They can
be developed into novel targeted cancer therapeutics. Dendrimers can be conjugated
to different biofunctional moieties such as folic acid using complementary DNA
oligonucleotides to produce clustered molecules, which target cancer cells that
over-express the high affi nity folate receptor.
Design of Future Personalized Cancer Therapies
A better understanding of cancer biology would enhance the design of future thera-
pies for cancer. For example, PCR can already be used to assess the effi cacy of new
therapies for leukemias. Future targets for cancer therapies may include defective
proto-oncogenes or the tumor suppressor genes themselves. A gene therapy strategy
might be employed to correct or replace the defective gene. In cancers with multi-
factorial etiology, it may be possible to interrupt one or two steps in the complex
pathways, thereby hindering the overall evolution of the tumor. Studies using serial
analysis of gene expression have shown that tumor and normal endothelium are
distinct at the molecular level, a fi nding that may have signifi cant implications for
the development of antiangiogenic therapies.
Mutant mice lacking cyclin D1 are entirely resistant to breast tumors induced by
neu and ras, genes implicated in most human breast cancers, but are susceptible to
those tumors caused by the other oncogenes c-myc and Wnt-1. Although it remains
to be seen whether these fi ndings translate to humans, the results suggest that human
breast cancers caused by neu and ras could be treated with anti-cyclin D1 therapy.
This would be personalized cancer therapy. Molecular profi les of breast-cancer
patients could be drawn up using DNA chips or assays.
Use of emerging technologies in early clinical trials is allowing quick assessment
of the effi cacy of anticancer agents. Cyclacel Ltd has introduced the concept of
assembling a toolkit that will allow rational drug development rather than a “trial
and error” method. Identifi cation of specifi c biomarker molecules in tumor tissue
will permit prediction of clinical outcomes in response to drug treatment. Such bio-
markers can be detected by a variety of techniques including immunohistochemis-
try, microarrays and qPCR. The cancer clinical trial toolkit, including biomarkers
that can detect antitumor activity of anticancer agents, can guide selection of patients
for specifi c drug treatments.
Design of Future Personalized Cancer Therapies