Molecular predictive factors of outcome of radiotherapy in cervical cancer

Abstract

Radical radiotherapy with concurrent cisplatin-based chemotherapy is an established treatment for cervical cancer patients with stage FIGO IIB and higher. The tumor control can be achieved in 40-80% of patients, the treatment is associated with the risk of late postiradiation complications in 10 -15% of cases. Detection of the factors predictive for tumor control and late morbidity is a possible direction how to individualize radiotherapy dose and technique. The aim of our review is to summarize results of studies inquiring various molecular markers predicting tumor response to radiotherapy and a risk of late complications.A lot of candidate molecules were evaluated in histochemical studies: membrane receptors (EGFR, HER-2), cell cycle regulators (p53, p21), proliferative markers (Ki-67), hypoxia and angiogenetic factors (HIF, VEGF), HPV status, and others (COX-2), with promising results in some of them (HPV, HIF-1α, Ku80, ATM polymorphism).Microarray studies identified decades of genes with different expression in radiosensitive/radioresistant cervical tumors and sets of genes are able to comletely separate responding and nonresponding tumors, but these sets differ across studies. Further well designed studies will be necessary to achieve results matured for use in clinical practice.

SULF2 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells through the ERK/AKT signaling pathway

“…According to global estimates, approximately 500,000 new cases of cervical cancer are diagnosed, 80% of which originate from developing countries, and 233,000 people die of this type of cancer worldwide every year (2). Although current treatments have resulted in great advancements in controlling tumor growth, most patients in the mid-term or advanced stage are still suffering from poor efficacy and prognosis (3,4). As reported previously, cervical cancer is a multistage and multigene network process involving epigenetic variation, immunological changes, and inactivation of tumor suppressor genes or activation of oncogenes (5,6).…”

7B7: a novel antibody directed against the Ku70/Ku80 heterodimer blocks invasion in pancreatic and lung cancer cells

“…It is normally found in the nucleus where it plays a key role in non-homologous end joining (NHEJ), a major pathway in DSB repairs in humans [26]. Ku70/Ku80 is a key mediator in NHEJ and has been implicated in the radiosensitivity of a number of cancer types including the bladder, lung, breast, glioma, prostate, head and neck and cervix [27][28][29][30][31][32][33][34]. Ku has also been reported to be involved in cisplatin chemoresistance of some aggressive cancers such as lung adenocarcinoma, ovarian and leukaemic cells [30,34].…”

Effect of Ku80 on the radiosensitization of cisplatin in the cervical carcinoma cell line HeLa

“…Cervical cancer is a common malignant tumor that has a detrimental impact on the life and health of women, particularly in developing countries. Surgery and radiotherapy are used to treat cervical cancer at stage IIA and earlier, whereas radiotherapy together with platinum chemotherapy sensitization constitutes the preferred treatment strategy for locally advanced (stage IIB and later) cervical cancer ( 1 ).…”