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Several molecular therapies are in development for gastric cancer.
Cyclooxygenase-2 (COX-2) is overexpressed in and correlated with gastric cancer,
and knockdown of COX-2 or administration of COX-2 inhibitors suppresses tumor
formation in models of gastric cancer. Induction of apoptosis, reduction of angio-
genesis, and blocking of potassium ion channels may present new mechanisms of
COX-2 inhibition. Osteopontin is a secreted protein involved in stress response,
infl ammation, wound healing, and immune response. Inhibition of osteopontin by
RNAi technique suppresses tumorigenesis as well as angiogenesis in gastric cancer.
Using HLA-A-matched allogeneic gastric cancer cells to induce tumor-specifi c
cytotoxic T lymphocytes is another option for personalized immunotherapy of gas-
tric cancer (Wu et al. 2009 ).
In ~22 % of cases, gastric cancer is HER2-positive. A phase III study has shown
that Herceptin (Genentech/Roche) is effective in advanced HER2-positive stomach
cancer and an application to FDA for approval is planned.
Personalized Management of Colorectal Cancer
Colorectal cancer (CRC) is one of the most common cancers in the world and is a
leading cause of cancer mortality and morbidity. CRC is the second most common
cause of cancer death in the US with ~150,000 Americans diagnosed yearly with the
disease. The cause of CRC is multifactorial, involving hereditary susceptibility,
environmental factors, and somatic genetic changes during tumor progression. Due
to a high degree of genetic and pathological heterogeneity, sporadic CRC is consid-
ered a collection of diseases that should be approached with different therapeutic
strategies. Integration of a new generation of molecularly targeted drugs into the
treatment of CRC, coupled with the development of sophisticated technologies for
individual tumors as well as patient molecular profi ling, form the bases of personal-
ized management of CRC.
Hereditary nonpolyposis CRC (HNPCC) is a familial cancer syndrome charac-
terized by mutations in at least one of six DNA mismatch repair genes: hPMS1,
hPMS2, hMSH2, MSH6, hTGFBR2 and hMLH1. From 5 % to 10 % of the 150,000
cases of CRC diagnosed each year in the US are of hereditary type. Identifi cation of
DNA microsatellite instability refi nes the diagnosis of HNPCC, allowing frequent
early-onset colonoscopic screening to be restricted to individuals with an especially
high risk of this type of cancer. It is possible that a combination of tests for micro-
satellite instability, allelic loss, p53 mutations, and other genetic alterations in
patients with early stage CRC will defi ne groups of patients who require different
adjuvant therapies or no systemic treatment at all. Despite the recent results of sys-
temic chemotherapy, more than 40 % of patients with advanced cancer still do not
achieve substantial benefi ts with cytotoxic agents. Therefore, personalized strate-
gies are warranted to improve the probability of disease control. It is important to
have a strategy for screening and early detection for preventive measures.
The NCI has developed absolute risk prediction models for CRC from population-
based data, and a simple questionnaire suitable for self-administration (Freedman
10 Personalized Therapy of Cancer