Does the mobilization of circulating tumour cells during cancer therapy cause metastasis?

Abstract

Despite progressive improvements in the management of patients with locoregionally confined, advanced-stage solid tumours, distant metastasis remains a very common - and usually fatal - mode of failure after attempted curative treatment. Surgery and radiotherapy are the primary curative modalities for these patients, often combined with each other and/or with chemotherapy. Distant metastasis occurring after treatment can arise from previously undetected micrometastases or, alternatively, from persistent locoregional disease. Another possibility is that treatment itself might sometimes cause or promote metastasis. Surgical interventions in patients with cancer, including biopsies, are commonly associated with increased concentrations of circulating tumour cells (CTCs). High CTC numbers are associated with an unfavourable prognosis in many cancers. Radiotherapy and systemic antitumour therapies might also mobilize CTCs. We review the preclinical and clinical data concerning cancer treatments, CTC mobilization and other factors that might promote metastasis. Contemporary treatment regimens represent the best available curative options for patients who might otherwise die from locally confined, advanced-stage cancers; however, if such treatments can promote metastasis, this process must be understood and addressed therapeutically to improve patient survival.

Circulating tumor cells and their clinical significance

“…[16] summarizes the current knowledge on the effects of anti-cancer treatment on mobilization of CTCs into the circulation. It was shown that different types of treatment applied to cure locoregional disease (i.e., radiotherapy, surgery, systemic therapies) may actually contribute to the increase in the number of CTCs in patients' blood, or an increase in proliferative capacity of CTCs.…”

The functions of circulating tumor cells in early diagnosis and surveillance during cancer advancement

“…[12] Despite progressive improvements in the management of patients with locoregionally confined, advanced-stage solid tumors, distant metastasis remains a very common -and usually fatal -mode of failure after attempted curative treatment. [13] Surgery and radiotherapy are the primary curative modalities for these patients, often combined with each other and/or with chemotherapy. [13] Surgical interventions in patients with cancer, including biopsies, are commonly associated with increased concentrations of CTCs.…”

“…[13] Surgery and radiotherapy are the primary curative modalities for these patients, often combined with each other and/or with chemotherapy. [13] Surgical interventions in patients with cancer, including biopsies, are commonly associated with increased concentrations of CTCs. [13] High CTC numbers are associated with an unfavorable prognosis in many cancers.…”

Rac1 is a potential target to circumvent radioresistance

“…Although IR showed positive therapeutic efficacy for many cancers, development of radioresistance, resulting in the tumor recurrence and metastasis involved multiple signaling pathways, remains a substantial clinical problem (5,6). The gene expressions affected by radiation therapy have been reported to be associated with anti-apoptosis, tumor aggressiveness, and enhanced metastatic potential such as resistance to hypoxia, invasiveness and motility, and epithelial-to-mesenchymal transition (EMT) (2). However, the critical regulator, which is involved in these processes and could be a potential target to circumvent radioresistance, has not been documented yet.…”

“…The most types of radiation commonly used for cancer treatment include X-rays, gamma rays and charged particles. Ionizing radiation (IR) induces DNA damage, resulting in either cell-cycle arrest or apoptosis (1,2), to show antitumor activity, and is used alone or in combination with surgery, chemotherapy or immunotherapy to benefit cancer patients at different stages (3). For example, radiation therapy is used for breast cancer of earlier stage following breastconserving surgery.…”