337Personalized Management of Gastrointestinal Cancer
Personalized Management of Esophageal Cancer
Esophageal cancer is highly aggressive malignancy. Almost half of new cases are
diagnosed at an advanced stage, when the 5-year survival rate is just 14 %. Surgery
is offered to most patients, as well as one or all of the following treatments: an anti-
metabolite chemotherapy agent (5FU), an alkylating agent (cisplatin) and radiation
treatment. Efforts are being made to evaluate esophageal cancer treatment with a
pharmacogenetic-based approach that takes into consideration genes in each drug
action pathway as a means of developing a more accurate and consistent risk predic-
tion model. Patients with resectable adenocarcinoma or squamous cell carcinoma of
the esophagus who have been treated with chemoradiation followed by esophagec-
tomy show that methylenetetrahydrofolate reductase polymorphisms can modify
5-fl uorouracil response. This supports the hypothesis that response or resistance to
therapy in esophageal cancer patients may be modulated by genetic variants involved
in the metabolism or mechanism of chemotherapy drug action. Further research on
esophageal cancer aims to determine individual pharmacogenetic profi les to iden-
tify patients most likely to have chemotherapeutic benefi t and patients with the
highest risk of suffering genotoxic side effects. These profi les will ideally lead to
individualized therapies, improved treatment outcomes, and a movement toward
clinically applied pharmacogenetics. This emergent area of biomedicine could lead
to substantially improved clinical outcomes for patients with adenocarcinoma or
squamous cell carcinoma of the esophagus. For example, a combination of several
gene variants in patients treated with one type of chemotherapy (5-FU) more than
doubled survival to in patients treated with the same drug who did not have these
variants. The fi ndings represent a signifi cant advance in the goal to provide person-
alized therapy because it offers a genetic blueprint for gauging the potential effec-
tiveness of all common esophageal cancer treatment, not just an analysis of how one
or two “candidate” genes respond to a single treatment. The patients with the best
outcomes are those who have gene variants that are less effective at neutralizing the
killing power of the cancer treatments. Conversely, patients whose genes effi ciently
counteract chemotherapy and radiation treatment have shorter survival times over-
all. If successful, such pathway-based analyses can be conducted for the wide vari-
ety of cancers that are treated with 5FU, cisplatin and radiation, as well as other
drug treatments.
Personalized Management of Gastric Cancer
Gastric cancer is the second most common cause of cancer death worldwide with
approximately one million cases diagnosed annually. Despite considerable improve-
ments in surgical techniques, innovations in clinical diagnostics and the develop-
ment of new chemotherapy regimens, the clinical outcome for patients with
advanced gastric cancer is generally poor with 5-year survival rates ranging between
5 % and 15 %.
Personalized Management of Cancers of Various Organs