Cancer treatment reviews
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Cancer treatment reviews · Dec 2015
ReviewUnderstanding and overcoming the mechanisms of primary and acquired resistance to abiraterone and enzalutamide in castration resistant prostate cancer.
In recent years, in castration resistant prostate cancer (CRPC), several new drugs have been approved that prolong overall survival, including enzalutamide and abiraterone, two new-generation hormonal therapies. Despite the demonstrated benefit of these agents, not all patients with CRPC are responsive to treatment, the gain in median progression-free survival with these therapies compared to standard of care is, rather disappointingly, still less than six months and the appearance of acquired resistance is almost universal. ⋯ Even if the mechanisms of resistance to these agents are not fully defined, many hypotheses are emerging, including systemic and intratumoral androgen biosynthesis up-regulation, androgen receptor (AR) gene mutations and amplifications, alteration of pathways involved in cross-talk with AR signaling, glucocorticoid receptor overexpression, neuroendocrine differentiation, immune system deregulation and others. The aim of this paper is to review currently available data about mechanisms of resistance to abiraterone and enzalutamide, and to discuss how these mechanisms could be potentially overcome through novel therapeutic agents.
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Cancer treatment reviews · Dec 2015
ReviewPD-1 and PD-L1 blockade in gastrointestinal malignancies.
Immunotherapy represents a major breakthrough in cancer therapy in recent years. Immune-checkpoint blockade using PD-1 and PD-L1 antibodies appears to be one of the most promising immunotherapy approaches. ⋯ In this review article, we explore the available evidence and summarise current clinical trials for PD-1 and PD-L1 blockade in gastrointestinal malignancies. The challenge now is to develop strategies to increase the efficacy of PD-1 and PD-L1 blockade in gastrointestinal cancer patients, such as combination therapy with chemotherapy, radiotherapy or other immunotherapy, along with validating biomarkers to select patients and personalise treatment.
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Cancer treatment reviews · Nov 2015
ReviewManaging synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus.
An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. ⋯ When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team.
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Cancer treatment reviews · Jul 2015
ReviewExtent of lymphadenectomy to associate with pancreaticoduodenectomy in patients with pancreatic head cancer for better tumor staging.
To define the extent of lymphadenectomy to associate with surgery for pancreatic head cancer. ⋯ A standard lymphadenectomy demands an adequate TNLE and removal of the LN stations metastasizing more frequently, without increasing the surgical risk.
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Cancer treatment reviews · Jun 2015
ReviewCombined BRAF and MEK inhibition for the treatment of BRAF-mutated metastatic melanoma.
Combined BRAF and MEK inhibition out-performed BRAF inhibitor monotherapy in 3 randomized Phase 3 studies for BRAF-mutated metastatic melanoma patients and the combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib is now an FDA-approved treatment in this setting. Nevertheless, the majority of patients face progressive disease even when treated with the combination. Mechanisms of resistance to BRAF inhibition have been extensively investigated, whilst less is known about the specific mechanisms of resistance to combined therapy. The aim of this paper is to review the efficacy and safety of the combination of BRAF plus MEK inhibitors compared with BRAF inhibitor monotherapy and immunotherapy, as well as to discuss the existing evidence for the mechanisms of resistance to combined therapy and assess future treatment strategies to improve outcome based on data provided by clinical and translational research studies.