Combined Therapy for Gastrointestinal Carcinomas: Exploiting Synergies Between Gene Therapy and Classical Chemo-Radiotherapy
Jorge B. Aquino,
Surgical resection is the only curative option for patients with gastrointestinal carcinomas.
Unfortunately, the majority of patients are diagnosed in advanced stages when surgery is not possible.
Moreover, the incidence and mortality for certain type of tumors such as hepatocellular carcinoma or
pancreatic cancer are steadily increasing worldwide. In spite of the advances in the development of
molecular targeted therapies for cancer, the impact on patient survival has been rather limited. It is unlikely
that individual agents would be ultimately successful as monotherapy. There is a growing area of research focused
on the combination of classical chemotherapy (e.g. cyclophosphamide, gemcitabine, paclitaxel and doxorubicin) with radiotherapy
and/or gene therapy strategies. Combined approaches seem to be required due to multiple resistance mechanisms
that tumors utilize to limit the activity of chemotherapeutic agents (e.g. the occurrence of multidrug resistance or
epigenetic alterations), evade immune responses (e.g. induction of regulatory T cells or myeloid-derived suppressor cells)
and to generate resistance against anti-angiogenesis or to radiotherapy by, for example, the induction of hypoxia-inducible
factor 1. In addition, new studies suggest that combination of low dose of conventional chemotherapy and gene therapy
could allow the development of synergic mechanisms able to achieve significant therapeutic effects against diverse tumors.
Although cancer gene therapy is not yet available in clinical practice, advances being recently made look promising,
especially when it was applied in combination with standard chemo- or radiotherapy protocols.
Keywords: Gastrointestinal, cancer, gene therapy, combined strategies, chemotherapy, radiotherapy, immunotherapy.
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