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Sammichele di Bari, Italy

Rizzo S.,University of Palermo | Bronte G.,University of Palermo | Fanale D.,University of Palermo | Corsini L.,University of Palermo | And 7 more authors.
Cancer Treatment Reviews | Year: 2010

An important molecular target for metastatic CRC treatment is the epidermal growth factor receptor (EGFR). Many potential biomarkers predictive of response to anti-EGFR monoclonal antibodies (cetuximab and panitumumab) have been retrospectively evaluated, including EGFR activation markers and EGFR ligands activation markers. With regard to the 'negative predictive factors'responsible for primary or intrinsic resistance to anti-EGFR antibodies a lot of data are now available. Among these, KRAS mutations have emerged as a major predictor of resistance to panitumumab or cetuximab in the clinical setting and several studies of patients receiving first and subsequent lines of treatment have shown that those with tumors carrying KRAS mutations do not respond to EGFR-targeted monoclonal antibodies or show any survival benefit from such treatments. The role of B-RAF mutations, mutually exclusive with KRAS mutations, in predicting resistance to anti-EGFR mAbs is not yet consolidated. It therefore appears that BRAF mutations may play a strong negative prognostic role and only a slight role in resistance to anti-EGFR Abs. © 2010 Elsevier Ltd. Source

Giuliani F.,Oncology Institute Bari | Colucci G.,Oncology Institute Bari | Colucci G.,Cancer Institute Giovanni Paolo II
Oncology | Year: 2010

As a result of progresses in surveillance programs and improvements in diagnosis, an increased number of hepatocellular carcinomas are diagnosed in early stage, when effective treatment options are available. Surgical resection, liver transplantation and radiofrequency ablation are considered potentially curative treatments and may be successfully applied when the disease is limited. In intermediate and advanced stages only palliative therapies can be employed and chemoembolization and the oral dual inhibitor sorafenib are considered the treatments of choice. Future directions will explore the role of sorafenib in the adjuvant setting, the addition of sorafenib to chemoembolization procedures and the combination of sorafenib with chemotherapeutic agents or other biological drugs in advanced stages of disease. Copyright © 2010 S. Karger AG. Source

Gnoni A.,Medical Oncology Unit | Marech I.,University of Bari | Silvestris N.,Cancer Institute Giovanni Paolo II | Vacca A.,University of Bari | Lorusso V.,Medical Oncology Unit
Current Drug Targets | Year: 2011

Dasatinib (BMS-354825, Sprycel ®) is an oral, multitargeted inhibitor of receptor tyrosine kinases (RTKs), including BCR-ABL fusion protein, stem cell factor receptor (c-KIT), platelet-derived growth factor receptor (PDGFR), and Src family kinases (SFKs). Several early- and late-phase clinical trials for chronic myelogeneous leukaemia (CML) have demonstrated the direct inhibition of BCR-ABL fusion protein and SFKs, which led to dasatinib approval by the Food and Drug Administration (FDA) and the European Union for the treatment of imatinib-resistant or -intolerant CML, and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Phase III dose-optimization study was performed to compare different regimens, stating that dasatinib 100 mg once daily is now the recommended schedule for patients with chronic CML, and 140 mg once daily for patients with accelerated phase or myeloid or lymphoid blast phase CML, and for patients with Ph+ ALL until progression. Because of the myriad of critical roles of SFKs in biological processes, SFKs inhibition could induce numerous biological responses. Ongoing clinical trials evaluate dasatinib in the treatment of several solid tumours, including gastrointestinal stromal tumours (GIST), prostate cancer, malignant pleural mesothelioma, sarcomas, NSCLC, colorectal cancer, glioblastoma and other haematologic malignances as multiple myeloma. Ongoing pre-clinical studies assess the therapeutic potential of dasatinib in other solid tumours, including melanoma, head and neck cancer, breast cancer and ovarian cancer. Dasatinib is generally well tolerated. Myelosuppression is the common adverse event which is, however, reversible by dose reduction, discontinuation, or interruption. Thrombocytopenia is more significant than neutropenia and associated to gastrointestinal bleeding and CNS haemorrhage. The most common non-haematologic adverse events include gastrointestinal symptoms (diarrhoea, nausea, vomiting, abdominal pain and anorexia), headache, peripheral edema, and pleural effusion. In respect of these encouraging studies investigating dasatinib in the treatment of patients with GIST, prostate cancer, multiple myeloma and sarcomas, ongoing phase III clinical trials warrant the drug evaluation as recommended agent for the treatment of these diseases, also in association with chemotherapy or other targeted therapies. © 2011 Bentham Science Publishers Ltd. Source

De Ceglie A.,Cancer Institute Giovanni Paolo II
Clinics and research in hepatology and gastroenterology | Year: 2011

Familial clusters of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) have been reported. This study evaluates the history of cancer in BE patients families. In two years, patients with BE (272), esophagitis (456) and controls (517) were recruited in 12 Italian Endoscopy Units. Cancer family history in first-degree (FD) relatives was determined by a questionnaire. Approximately 53% of BE, 51% of esophagitis, and 48% of controls had at least one relative affected by any type of malignancy. Probands with at least one esophageal or gastric (E/G) cancer-affected relative showed a BE risk which was at least eighty-five percent higher than that of probands without affected relatives. The relative risk of BE was 4.18, 95% CL=0.76-23.04 if a FD relative had early (mean age ≤ 50 years) onset E/G cancer compared to late onset E/G cancer. In this sample there was no evidence that a family history of cancer was associated with the diagnosis of BE. An intriguing result was the association between the occurrence of E/G cancers at earlier ages (< 50 years) among BE relatives with respect the control group. This could suggest a genetic contribution in onset of these tumors, but the sample was too small to demonstrate a significant association. Further exploration of family history of E/G cancer and a diagnosis of BE in larger samples is warranted. Copyright © 2011 Elsevier Masson SAS. All rights reserved. Source

Bronte G.,University of Palermo | Rizzo S.,University of Palermo | La Paglia L.,University of Palermo | Adamo V.,Messina University | And 7 more authors.
Cancer Treatment Reviews | Year: 2010

The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as ' driver mutations' These are responsible for both the initiation and maintenance of the malignancy. The epidermal growth factor receptor (EGFR) pathway is the main regulator of cell function and cancer development. It has a widely defined role in the occurrence of driver mutations. Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma. In this review we report the molecular bases that have led to the clinical application of the detection for such genetic impairments. Subsequently we discuss the clinical studies regarding the prognostic role and the predictive value for response to anti-EGFR tyrosine kinase inhibitors (TKI) of the same mutations. We also provide a potential algorithm as a guide in the choice of the best treatment for patients with adenocarcinoma. © 2010 Elsevier Ltd. Source

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