Individualised cancer therapeutics: dream or reality?
Traditional measures for treating metastatic cancer involve identification of the originating organ from which the neoplasm arose and empirical treatment with cytotoxic chemotherapy. Arguably, with the exception of haematological malignancies, demonstration of efficacy in solid tumours has been limited. Over the past half-decade, theoretical and technological advances have resulted in greater application of molecular science to drug design, which has enabled development of new 'targeted' therapeutics. However, generic chemotherapy paradigms have not changed. Establishment of the optimal population for 'targeted' therapeutics based on molecular diagnostics (i.e. genomic and proteomic characterisation) to identify sensitive tumour-host ecosystems in individual patients at the 'bedside', is not being done as part of routine oncology management. This review focuses on the concept of designing individualised therapeutics based on genomic and proteomic profile of malignant tissue. Genetic and epigenetic perturbations in signal pathways drive cancer growth, survival, invasion and metastatic spread. The burgeoning evidence which supports the concept that each patient's cancer has a unique complement of pathogenic genetic and molecular derangements is reviewed. Such evidence supports the strategy of individualised selection of a therapeutic complex from a menu of targeting options that best complements the specific oncomolecular profile of the 'tumour-host' system.
Senzer
Neil
N
Mary Crowley Medical Research Center, Collins Building, Suite 302, Dallas, TX 75246, USA.
Shen
Yuqiao
Y
Hill
Colin
C
Nemunaitis
John
J
D000970:Antineoplastic Agents / Q000008:administration & dosage; D018390:Gene Targeting / Q000379:methods / Q000639:trends; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D010597:Pharmacogenetics / Q000379:methods* / Q000639:trends*; D040901:Proteomics / Q000379:methods / Q000639:trends
D000970:Antineoplastic Agents