Abstract:
INTRODUCTION:PI3K inhibitors are an important new therapeutic option for the treatment of relapsed and refractory B-cell lymphoid malignancies. Idelalisib is a PI3Kδ inhibitor that has been approved for the treatment of lymphoma and chronic lymphocytic leukemia in the relapsed/refractory setting, and several other PI3K inhibitors are being developed targeting other isoforms of the PI3K enzyme, which results in distinct toxicities and variable efficacy in the clinical setting. Areas covered: We provide a general overview of PI3K inhibitors, recommended applications, and the mechanism and management of toxicities. We further review trials, ongoing and completed, leading to the approval of idelalisib as well other PI3K inhibitors currently in development. Articles were obtained from PubMed, and abstracts were searched for the past 5 years from the websites for ASCO, ASH, EHA, and ICML/Lugano. Expert commentary: PI3K inhibitors provide an important and powerful pharmacologic tool in the armamentarium against hematologic malignancies, especially for relapsed/refractory B-cell lymphoid malignancies. Unique toxicities are associated with inhibition of different isoforms of the PI3K enzyme, as demonstrated with the infectious and autoimmune toxicities associated with the PI3Kδ inhibitor, idelalisib. Due to these unique toxicities, PI3K inhibitors should only be used in formally approved combinations and settings.
journal_name
Expert Rev Anticancer Therjournal_title
Expert review of anticancer therapyauthors
Greenwell IB,Flowers CR,Blum KA,Cohen JBdoi
10.1080/14737140.2017.1285702subject
Has Abstractpub_date
2017-03-01 00:00:00pages
271-279issue
3eissn
1473-7140issn
1744-8328journal_volume
17pub_type
杂志文章,评审abstract::Introduction: Prodrugs have been used to improve the selectivity and efficacy of cancer therapy by targeting unique abnormal markers that are overexpressed by cancer cells and are absent in normal tissues. In this context, different strategies have been exploited and new ones are being developed each year. Areas cover...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1080/14737140.2019.1615890
更新日期:2019-06-01 00:00:00
abstract::Rapid malignant proliferation, prior to effective tumor neoangiogenesis, creates a microenvironment around solid cancers, which is predominantly hypoxic and characterized by a high interstitial fluid pressure. Presumably as an adaptive response, tumor cells favor metabolic activity with apparently inefficient energy o...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.2013.843455
更新日期:2013-10-01 00:00:00
abstract::The management of renal tumors has evolved rapidly over the last two decades, with the ascendance of nephron-sparing surgery (NSS), largely spurred by the increased incidental detection of small renal masses (SRMs) and evidence that preservation of renal parenchyma reduces the risk of chronic kidney disease. The field...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.8.12.1899
更新日期:2008-12-01 00:00:00
abstract::Immunotherapies such as sipuleucel-T present new and unique challenges for the optimal timing and sequencing of therapies for metastatic castration-resistant prostate cancer (mCRPC). Key considerations for the sequencing of sipuleucel-T are its unique proposed mechanism of action, the time required to generate a clini...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.2014.848065
更新日期:2014-01-01 00:00:00
abstract::It has been evident for some time that individuals from some families exhibit a genetic predisposition to breast cancer. Since the discovery of the first breast cancer susceptibility gene, BRCA1 in the 1990s, much work has been carried out to identify further breast cancer susceptibility genes. This has led to the ide...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/era.09.38
更新日期:2009-08-01 00:00:00
abstract::Anemia is a frequent problem in cancer patients, especially in those treated with chemotherapy, and has an important negative impact on quality of life. Red blood cell transfusions provide clear but rather temporary comfort. The development of erythropoietic stimulating agents (ESAs) led to a more durable anemia treat...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.7.10.1347
更新日期:2007-10-01 00:00:00
abstract::Although testicular cancer is currently a rare disease, the incidence is rising. The most important risk factor remains cryptorchism and there is a variable association with testicular microlithiasis. Serum tumor markers remain important for diagnosis, and they have prognostic value and can be used to monitor therapy ...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.4.4.669
更新日期:2004-08-01 00:00:00
abstract:INTRODUCTION:Mesothelioma is a rare type of cancer that is strongly tied to asbestos exposure. Despite application of different modalities such as chemotherapy, radiotherapy and surgery, patient prognosis remains very poor and therapies are ineffective. Much research currently focuses on the application of novel approa...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1080/14737140.2017.1358091
更新日期:2017-09-01 00:00:00
abstract::Soft tissue sarcomas are a diverse group of rare tumors that comprise 1% of all cancers. Few randomized trials of chemotherapy have been performed but there is a clear role for agents such as doxorubicin and ifosfamide in the palliation of advanced disease. There is uncertainty as to whether sequential single-agent tr...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/era.09.176
更新日期:2010-02-01 00:00:00
abstract::Medical therapy represents an alternative treatment approach that can be considered for some forms of non-melanoma skin cancer (NMSC). In selected cases, topical treatments are preferable to invasive procedures, especially in the case of multifocal lesions, unclear lesion edges, risk of keloids, surgical risk factors ...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.2013.856759
更新日期:2013-12-01 00:00:00
abstract::Small cell carcinoma of the urinary bladder (SCCUB) is a rare and aggressive disease. To date, no standard treatment has been proposed due to the lack of prospective studies resulting from the rarity of this disease. Recently published studies of relatively large patient cohorts, however, have shed some light on the m...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.2013.851605
更新日期:2013-11-01 00:00:00
abstract::Since its first description nearly two centuries ago, melanoma has been a difficult disease to diagnose and treat. With the incidence and mortality rates slowly increasing, understanding this disease is more important than ever. Herein, the current diagnostic and treatment recommendations for melanoma of the head and ...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.3.5.673
更新日期:2003-10-01 00:00:00
abstract::For many decades, the use of chemotherapy as second-line therapy in non-small-cell lung cancer relied upon disease progression. Several studies have shown that four to six cycles of chemotherapy administered as front-line therapy treatment offers a survival advantage to patients; however, further chemotherapy beyond t...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/era.10.30
更新日期:2010-04-01 00:00:00
abstract::In this report, we first describe the history of transsphenoidal surgery. We further elaborate on three fundamental surgical anatomy principles of transsphenoidal surgery for pituitary adenomas. First, the pituitary gland and, therefore, pituitary adenomas are extra-arachnoid structures, therefore the operation should...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.6.9s.S75
更新日期:2006-09-01 00:00:00
abstract::The prospects for the treatment of metastatic melanoma are improving. Whereas previous scientific meetings dedicated to the treatment of metastatic melanoma patients were overshadowed by our inability to improve overall survival or lengthen the time to progression, the results presented at the most recent meetings are...
journal_title:Expert review of anticancer therapy
pub_type:
doi:10.1586/era.11.62
更新日期:2011-06-01 00:00:00
abstract::The incidence of renal cell cancer is increasing and surgery is the only curative treatment for patients presenting with localized disease at diagnosis. The treatment of metastatic renal cell cancer is palliative and, until recently, immunotherapy has been the standard treatment approach with response rates between 10...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.7.1.57
更新日期:2007-01-01 00:00:00
abstract::In the new era of 'precision' cancer medicine, new drug development has shifted from cytotoxic chemotherapy to molecularly targeted agents. Eribulin mesylate, a microtubule-destabilizing agent, is the only 'classical' cytotoxic agent approved for the treatment of breast cancer in the last 7 years. This synthetic analo...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.2014.920693
更新日期:2014-06-01 00:00:00
abstract::There is increasing interest in the use of prognostic markers that may predict survival and guide management in patients diagnosed with the early stages of chronic lymphocytic leukemia (CLL). Currently, the most important traditional prognostic factors include clinical staging, lymphocyte doubling time and β2-microglo...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/era.12.2
更新日期:2012-03-01 00:00:00
abstract::Since its approval by the US FDA in 1986, prostate-specific antigen (PSA) has been employed to monitor men with a diagnosis of prostate cancer. In 1994, PSA was approved for use in prostate cancer screening and has been employed worldwide. However, due to the limited specificity of PSA for the disease, novel biomarker...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/era.09.168
更新日期:2010-01-01 00:00:00
abstract::With the introduction of orally-active, potent and selective third-generation aromatase inhibitors and inactivators--anastrozole, letrozole and exemestane--approaches to the treatment of advanced breast cancer are undergoing re-evaluation. In advanced breast cancer, aromatase inhibitors and inactivators are likely to ...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.2.3.267
更新日期:2002-06-01 00:00:00
abstract:INTRODUCTION:Despite a variety of therapies for advanced metastatic colorectal cancer being available, the outcomes in this malignancy remain suboptimal. Immunotherapy has been slow to impact the management of this patient group. Checkpoint inhibitors, such as nivolumab, have had disappointing results when used broadly...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1080/14737140.2018.1480942
更新日期:2018-07-01 00:00:00
abstract::Crizotinib (XALKORI™, Pfizer) is a tyrosine kinase inhibitor targeting ALK, MET and ROS1, currently approved for the treatment of adults with ALK-rearranged non-small-cell lung cancer. Optimizing the management of frequent crizotinib-related adverse events is crucial to ensure its continuous administration and reprodu...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.2014.986103
更新日期:2015-02-01 00:00:00
abstract::Cardiac toxicity is one of the most important long-term toxicities experienced by cancer survivors so that survival rate due to anticancer therapy may be negatively affected due to cardiac complications. Thus, the search for novel methods to lower the incidence of treatment-related cardiotoxicity is a priority for all...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.2015.1047766
更新日期:2015-01-01 00:00:00
abstract::Nonmelanoma skin cancer is the most prevalent malignant disease among light-skinned individuals in the USA, accounting for approximately 1 million new cases annually. Solar ultraviolet radiation is known to be the major cause of skin cancer. The idea that diet, particularly dietary fat, may play a role in modulating c...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.5.5.801
更新日期:2005-10-01 00:00:00
abstract::Genomics has generated a wealth of data that is now being used to identify additional molecular alterations associated with cancer development. Mapping these alterations in the cancer genome is a critical first step in dissecting oncological pathways. There are two ways in which cancer research has changed in recent y...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.3.6.891
更新日期:2003-12-01 00:00:00
abstract::Increased cancer risk after renal transplantation is believed to be a consequence of continuous immunosuppression. However, the risk of colorectal cancer (CRC) after renal transplantation is controversial and has received limited study. Accumulating evidence suggests that colon and rectal cancers have different charac...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.8.8.1339
更新日期:2008-08-01 00:00:00
abstract::One of the most prominent pathways explored in the area of targeted therapy is the PI3K/Akt/mTOR pathway, which plays a central role in cell survival and proliferation. Deregulation of this pathway has been implicated in the promotion of cancer cell growth and survival. Inhibition of several steps of this pathway has ...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1586/14737140.6.1.131
更新日期:2006-01-01 00:00:00
abstract::Until now, no effective systemic treatment options have been available for patients with unresectable advanced hepatocellular carcinoma (HCC). In the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP), patients with unresectable advanced HCC with Child-Pugh liver function class A and who had not...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章
doi:10.1586/era.09.41
更新日期:2009-06-01 00:00:00
abstract:INTRODUCTION:Tamoxifen, as an essential therapeutic tool in the treatment of estrogen receptor-positive breast cancer, has been available for the past three decades and is currently being utilized as a chemo-preventive agent for patients at high risk for breast carcinoma. However, the induction of chemo-resistance duri...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1080/14737140.2017.1340837
更新日期:2017-07-01 00:00:00
abstract:INTRODUCTION:About 50% of all patients with advanced testicular cancer demonstrate residual retroperitoneal or extraretroperitoneal masses. About two thirds of the masses harbour necrosis/fibrosis only whereas as about 10% and 40% harbour vital cancer or teratoma. Appropriate therapy will result in a high cure rate if ...
journal_title:Expert review of anticancer therapy
pub_type: 杂志文章,评审
doi:10.1080/14737140.2019.1580146
更新日期:2019-04-01 00:00:00