Phases of tumor progression

Fig. 5.1 Phases of cancer progression. When normal cells or tissues are subjected to genotoxic, cytotoxic, or carcinogenic insult, they may undergo transformation in a nitric-oxide-dependent manner. This process is characterized by activation of signaling cascades that result in increased proliferation and inhibition of apoptosis, causing neoplastic evolution in the process, which is accompanied by various biophysical and biochemical changes. Once the tumor is established, the release of angiogenic mediators is stimulated, leading to increased blood vessel formation, accompanied with increased vascularization of the tumor. Finally, in the metastatic phase, the tumors develop migratory and invasive properties that facihtate dissemination of the tumor and metastasis to secondary sites...

In tumor progression, the acquisition of a motile/migratory phenotype is a process that generally coincides with the switch to a malignant phase. This is achieved either by local invasion/infiltration... 

Takeda et al. (64) performed a phase I/II study consisting of low-dose CDDP (6-10 mg/m2/d) and UFT (600 mg/d) combined with radiotherapy (50 Gy/25 fractions) as postoperative adjuvant therapy following curative resection for patients with nonsmallcell lung cancer (NSCLC). The combined therapy was well tolerated and resulted in a disease-free survival rate of 78% at 2 yr. Another study in a small number of patients with unresectable stage III nonsmall-cell lung cancer, UFT (400 mg/m2 on d 1-52) and CDDP (80 mg/m2 on d 8,29, and 50) were administered with radiation therapy (total dose of 60.8 Gy in 38 fractions on d 1-52). Among 17 evaluable patients, 94% (16 patients) achieved partial responses with median time to tumor progression of 30 wk, and the... 

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