Abstract：
:Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches. The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes. Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy. This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors.
journal_name
Cancer Treat Revjournal_title
Cancer treatment reviewsauthors
Corti F,Nichetti F,Raimondi A,Niger M,Prinzi N,Torchio M,Tamborini E,Perrone F,Pruneri G,Di Bartolomeo M,de Braud F,Pusceddu Sdoi
10.1016/j.ctrv.2018.11.001subject
Has Abstractpub_date
2019-01-01 00:00:00pages
45-55eissn
0305-7372issn
1532-1967pii
S0305-7372(18)30185-3journal_volume
72pub_type
杂志文章,评审abstract：:From a theoretical viewpoint, intraperitoneal therapy (IP) in patients with ovarian cancer, a malignancy which remains mainly confined to the peritoneal cavity, is logical. Over the past decades this approach has evolved into a therapeutic strategy for a selected group of patients. Data available at present suggest a ...
journal_title：Cancer treatment reviews
pub_type： 杂志文章
doi：10.1053/ctrv.1999.0152
更新日期：2000-04-01 00:00:00
abstract：:Metastatic melanoma is an incurable condition with a median survival of about 6 months. Chemotherapy can result in objective tumour responses but only in a minority of cases and remissions are short-lived, 3-6 months. DTJC is the most active single agent with response rates of 15-20% and although combination chemother...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1053/ctrv.1999.0138
更新日期：1999-10-01 00:00:00
abstract：:The prognosis for patients with relapsed/progressive non-small cell lung cancer (NSCLC) remains poor. For first-line therapy, a number of platinum-based regimens are standard; second-line therapies include single-agent docetaxel, pemetrexed, and erlotinib. Treatment options for patients whose tumors have failed to res...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2012.05.003
更新日期：2013-05-01 00:00:00
abstract：:Solid tumours contain regions of hypoxia, which may be a prognostic indicator and determinant of malignant progression, metastatic development and chemoradio-resistance. The degree of intra-tumoural hypoxia has been shown to be positively correlated with the expression of the transcription factor hypoxia-inducible fac...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2006.05.003
更新日期：2006-10-01 00:00:00
abstract：:RAS family proteins (including KRAS and NRAS) play important roles in the epidermal growth factor receptor (EGFR) signaling pathway. Mutations in RAS genes (occurring at loci in exons 2, 3, and 4) often result in constitutive activation of RAS proteins and persistent downstream signaling. Mutations in KRAS exon 2 (cod...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2015.05.008
更新日期：2015-09-01 00:00:00
abstract：:Oxaliplatin is widely regarded as being active in cisplatin-resistant cancer. We undertook a systematic review of the literature to identify, describe and critique the clinical and pre-clinical evidence for the use of oxaliplatin in patients with "cisplatin-resistant" cancer. We identified 25 pre-clinical cell models ...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2007.01.009
更新日期：2007-06-01 00:00:00
abstract：:Non-small cell lung cancer (NSCLC) is the biggest cancer killer in the United States and worldwide. In 2011, there are estimated to be 221,130 new cases of lung cancer in the United States. Over a million people will die of lung cancer worldwide this year alone. When possible, surgery to remove the tumor is the best t...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2011.11.008
更新日期：2012-10-01 00:00:00
abstract：:Metastatic breast cancer is ultimately an incurable disease, although recent data have shown that its incidence is decreasing and that patients with metastatic breast cancer live longer. This improvement in survival seems to be linked with the introduction of new therapeutic agents, novel combinations of existing ther...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2009.10.001
更新日期：2010-02-01 00:00:00
abstract：:The use of endocrine therapy is well established as a primary treatment for locally advanced breast cancer. However, despite the current popularity of neoadjuvant chemotherapy for operable tumours, there is relatively little published evidence for pre-operative endocrine therapy in operable disease, particularly outsi...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2006.10.003
更新日期：2007-02-01 00:00:00
abstract：:In the last ten years, the development of several novel targeted drugs and the refinement of state of the art technologies such as the genomics and proteomics and their introduction to clinical practice have revolutionized the management of patients affected by cancer. However, everyday practice points out several cli...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2007.10.001
更新日期：2008-04-01 00:00:00
abstract：:We have established that drug resistance can be expressed following in vitro exposure of tumour cells not only to antitumor drugs but also to fractionated X-irradiation. These data therefore suggest a biological basis for the clinical problem of drug resistance that can occur in patients with previously irradiated tum...
journal_title：Cancer treatment reviews
pub_type： 杂志文章
doi：10.1016/0305-7372(90)90012-5
更新日期：1990-12-01 00:00:00
abstract：:Metastatic colorectal cancer (CRC) is most frequently seen in the liver. Resection of metastases remains the treatment of choice; however, the majority of patients are ineligible for surgery due to unfavorable location, size, or number of metastases; insufficient liver reserve; or extrahepatic disease. The activity of...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2008.01.004
更新日期：2008-06-01 00:00:00
abstract：:Two regimens were tested, CHAP I and CHAP II, the latter, a hexamethylmelamine dosage-intensive regimen, first as second line (salvage) therapy and then as primary therapy. Both produced the most successful results achieved in the Mount Sinai series up to the time of their introduction, when compared to their predeces...
journal_title：Cancer treatment reviews
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/0305-7372(91)90025-u
更新日期：1991-03-01 00:00:00
abstract：:Cyclophosphamide is considered one of the most successful chemotherapy drugs and is listed on the World Health Organisations List of Essential Medicines. Since its initial synthesis in 1958, it has been widely used to treat a range of cancers but its use has been declining due to the advent of platinum based and other...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2015.11.005
更新日期：2016-01-01 00:00:00
abstract：INTRODUCTION:Identification of membrane proteins expressed exclusively on tumor cells is a goal for cancer drug development. The receptor tyrosine kinase-like orphan receptor type 1 and 2 (ROR1/2), are type-I transmembrane proteins expressed in cancer but not in adult normal tissue. Here, we explore the prognostic role...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,meta分析
doi：10.1016/j.ctrv.2019.05.006
更新日期：2019-07-01 00:00:00
abstract：:Surgery is, and always has been, the main treatment modality of solid tumours. For a long period, it consisted of a number of surgical procedures dictated by basic oncologic principles, most of which are still adhered to. Over the last few decades, increased understanding of the disease, new or improved diagnostic fac...
journal_title：Cancer treatment reviews
pub_type： 历史文章,杂志文章,评审
doi：10.1053/ctrv.1999.0147
更新日期：1999-12-01 00:00:00
abstract：:Resistance to tyrosine-kinase inhibitors remains an open issue in the treatment of patients with gastrointestinal stromal tumors. The complex biology of disease in the multi-resistant setting has led a progressively growing urgency and interest in development combined or integrated therapies. This mini-review outlines...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2009.10.004
更新日期：2010-02-01 00:00:00
abstract：PURPOSE:To summarize and define the methodological quality of primary research findings obtained in exercise interventions, aimed at improving physical function or psychological well-being in patients treated for haematological malignancies. METHODS:Relevant trials were identified through a computerized Mesh-search in...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2008.09.008
更新日期：2009-04-01 00:00:00
abstract：:Chemokines are proteins which induce chemotaxis, promote differentiation of immune cells, and cause tissue extravasation. Given these properties, their role in anti-tumor immune response in the cancer environment is of great interest. Although immunotherapy has shown clinical benefit for some cancer patients, other pa...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2017.11.007
更新日期：2018-02-01 00:00:00
abstract：:Peptide receptor radionuclide therapy (PRRT) is an important therapeutic option for somatostatin receptor (SSTR) positive metastatic and/or inoperable neuroendocrine tumours (NETs). However, in patients with poorly controlled carcinoid syndrome, it may lead to an acute flare of carcinoid symptoms or even carcinoid cri...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2018.03.002
更新日期：2018-05-01 00:00:00
abstract：:Borderline ovarian tumours (BOT) may occur in young women and have an excellent survival rate. Therefore, there is the obligation to put emphasis on fertility preservation in affected women. On the other hand, it has also been underlined that the disease should be managed with caution because these tumours can relapse...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2016.06.010
更新日期：2016-09-01 00:00:00
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journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2017.04.003
更新日期：2017-05-01 00:00:00
abstract：:Glioblastomas are the most common malignant primary intrinsic brain tumors. Their incidence increases with age, and males are more often affected. First-line management includes maximum safe surgical resection followed by involved-field radiotherapy plus concomitant and six cycles of maintenance temozolomide chemother...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2020.102029
更新日期：2020-07-01 00:00:00
abstract：:Approximately 5-10% of breast cancer cases might be inheritable, up to 30% of which are due to BRCA1/2 mutations. During the past few years and thanks to technology evolution, we have been witnesses of an intensive search of additional genes with similar characteristics, under the premise that successful gene discover...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2014.10.008
更新日期：2015-01-01 00:00:00
abstract：:Glioblastoma is the most malignant and frequent primary brain tumour in adults. Current treatment remains insufficient as these tumours display a diffuse infiltrative growth pattern and tend to recur despite extensive debulking surgery followed by radio- and chemotherapy. The alkylating agents carmustine (1,3-bis-(2-c...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2008.03.125
更新日期：2008-10-01 00:00:00
abstract：:Recent advances in RNA delivery and target selection provide unprecedented opportunities for cancer treatment, especially for cancers that are particularly hard to treat with existing drugs. Small interfering RNAs, microRNAs, and antisense oligonucleotides are the most widely used strategies for silencing gene express...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2016.08.004
更新日期：2016-11-01 00:00:00
abstract：BACKGROUND:Patients who are diagnosed with cancer want advice on how they may alter their diet or which diet supplements they should take to augment chemotherapy. METHODS:We conducted a review of the literature mostly from the last 15 years on the interaction between dietary constituents and antineoplastic therapy in ...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2006.12.004
更新日期：2007-05-01 00:00:00
abstract：:Up to one in four patients with nasopharyngeal carcinoma present with non-metastatic stage IV disease (i.e. T4 or N3). Distinct failure patterns exist, despite the routine adoption of contemporary treatment modalities such as intensity modulated radiotherapy and systemic chemotherapy. Concurrent chemoradiotherapy (CCR...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2020.101995
更新日期：2020-04-01 00:00:00
abstract：:Despite the initially high response rate to standard front-line debulking surgery followed by platinum-based chemotherapy, the relapse rate in ovarian cancer is high and many patients will recur within 6 months of completing platinum based treatment. These patients may still require further chemotherapy despite being ...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/j.ctrv.2012.04.004
更新日期：2013-04-01 00:00:00
abstract：:Despite recent progress in the diagnostic and therapeutic approaches to the management of women with breast cancer, at least one third of these women will ultimately die from their disease. This resulted in a new focus on breast cancer prevention, especially for the woman designed as "high-risk". The continuing challe...
journal_title：Cancer treatment reviews
pub_type： 杂志文章,评审
doi：10.1016/s0305-7372(02)00107-x
更新日期：2003-04-01 00:00:00
