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https://www.readbyqxmd.com/read/28096940/the-next-10-years-challenges-for-the-future-and-overcoming-resistance-to-targeted-therapies-for-renal-cell-carcinoma
#1
REVIEW
Daniel Y C Heng
The introduction of targeted therapies over the past 10 years revolutionized the treatment of metastatic renal cell carcinoma (mRCC). The next 10 years hold promise for even greater expansion of the therapeutic armamentarium for mRCC. A number of recently completed and ongoing trials have explored the use of antivascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors in the adjuvant setting, the use of predictive biomarkers to guide personalized medicine, as well as new systemic treatments and combination therapies for mRCC...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28093990/insight-to-pharmacokinetics-of-tkis-optimizing-practical-guidelines-for-individualized-therapy
#2
Ruiqing Wang, Chaoqin Zhong, Chen Zhang, Mingqiang Hua, Daoxin Ma
Tyrosine kinase inhibitors (TKIs) are widely used drugs which have high availability in reducing the activity of BCR-ABL1 tyrosine kinase, therefore they play an indispensable role in the treatment of Chronic myeloid leukemia (CML). Imatinib, dasatinib and nilotinib have been proved to have absolute bioavailability and stable blood concentration in humans. TKIs pharmacokinetics has close relationships with the clinical response and clinical treatment of CML. We conducted a systematic PubMed search to look for studies relating to TKIs pharmacokinetics with proper inclusion/exclusion criteria...
January 16, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28093061/polyphyllin-ii-restores-sensitization-of-the-resistance-of-pc-9-zd-cells-to-gefitinib-by-a-negative-regulation-of-the-pi3k-akt-mtor-signaling-pathway
#3
Ruzhen Zheng, Hao Jiang, Jinhui Li, Xinge Liu, Hongwei Xu
: EGFR tyrosine kinase inhibitors (TKIs) are widely used for advanced non-small cell lung cancer (NSCLC) patients with a sensitizing EGFR mutation and provide a promising treatment strategy. However, acquired resistance to EGFR-TKIs restrict their application. The mechanisms underlying acquired resistance to TKIs have been explored and Phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway plays a very important role in NSCLC development as well as EGFR-TKI resistance. Polyphyllin II(PP II) is the main steroidal saponin constituent which derives from the root of Paris polychylia...
December 13, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28090366/bosutinib-therapy-in-patients-with-chronic-myeloid-leukemia-practical-considerations-for-management-of-side-effects
#4
REVIEW
Patricia S Ault, John Rose PharmD, Lisa A Nodzon PhD, Elizabeth S Kaled
The past decade has witnessed great advances in the treatment of chronic myeloid leukemia (CML), brought about in large part by the development of BCR-ABL tyrosine kinase inhibitors (TKIs). Bosutinib joins the armamentarium of approved TKIs for the treatment of chronic phase (CP), accelerated phase (AP), and blast phase (BP) Philadelphia chromosome (Ph)-positive CML resistant to or intolerant of prior therapy. Bosutinib has an adverse-event (AE) profile distinct from that of other TKIs. Diarrhea is the predominant toxicity associated with bosutinib treatment; other commonly reported nonhematologic AEs include rash and liver enzyme elevations...
March 2016: Journal of the Advanced Practitioner in Oncology
https://www.readbyqxmd.com/read/28089942/targeting-egfr-t790m-mutation-in-nsclc-from-biology-to-evaluation-and-treatment
#5
Antonio Passaro, Elena Guerini-Rocco, Alessia Pochesci, Davide Vacirca, Gianluca Spitaleri, Chiara Matilde Catania, Alessandra Rappa, Massimo Barberis, Filippo de Marinis
The identification of EGFR mutations and their respectively tyrosine kinase inhibitors (TKIs), changed dramatically treatment and survival of patients with EGFR-positive lung cancer. Nowadays, different EGFR TKIs as afatinib, erlotinib and gefitinib are approved worldwide for the treatment of NSCLC harbouring EGFR mutations, in particular exon 19 deletions or exon 21 (Leu858Arg) substitution EGFR mutations. In first-line setting, when comparing with platinum-based chemotherapy, these target drugs improves progression-free survival, response rate and quality of life...
January 12, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28089721/angiotensin-inhibitors-as-treatment-of-sunitinib-pazopanib-induced-hypertension-in%C3%A2-metastatic-renal-cell-carcinoma
#6
Patrick Penttilä, Juhana Rautiola, Tuija Poussa, Katriina Peltola, Petri Bono
BACKGROUND: Research suggests that baseline use of angiotensin system inhibitors (ASIs) improves outcome in patients with metastatic renal cell carcinoma (mRCC), but it remains unknown whether the type of antihypertensive medication used to initiate management at onset of treatment-induced hypertension (HTN) is associated with outcome. We evaluated the association of ASIs and outcome among patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs). PATIENTS AND METHODS: We identified 303 consecutive patients with mRCC who were treated with sunitinib or pazopanib in a single university hospital cancer center...
December 22, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28089594/epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-sensitive-exon-19-insertion-and-exon-20-insertion-in-patients-with-advanced-non-small-cell-lung-cancer
#7
Yen-Ting Lin, Yi-Nan Liu, Shang-Gin Wu, James Chih-Hsin Yang, Jin-Yuan Shih
BACKGROUND: The clinical responsiveness to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with exon 19 insertion and the specific exon 20 insertion (A763_Y764 insFQEA) are still not well known. MATERIALS AND METHODS: We analyzed cancer specimens taken from NSCLC patients for EGFR mutations using RNA reverse transcription polymerase chain reaction or direct DNA sequencing. The clinical course and responsiveness to an EGFR TKI in patients with EGFR exon 19 insertion or exon 20 insertion (A763_Y764 insFQEA) were recorded...
December 28, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28089159/immunohistochemistry-for-egfr-mutation-detection-in-non-small-cell-lung-cancer
#8
Nina Turnšek Hitij, Izidor Kern, Aleksander Sadikov, Lea Knez, Karmen Stanič, Matjaž Zwitter, Tanja Cufer
INTRODUCTION: The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation-positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing. METHODS: The trial included 79 consecutive EGFR mutation-positive and 29 EGFR mutation-negative NSCLC cases diagnosed with reflex PCR-based testing...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#9
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088233/successful-recovery-from-a-subclavicular-ulcer-caused-by-lenvatinib-for-thyroid-cancer-a-case-report
#10
Morimasa Kitamura, Tomomasa Hayashi, Chiaki Suzuki, Shigeru Hirano, Ichiro Tateya, Yo Kishimoto, Koichi Omori
BACKGROUND: There are currently no effective therapeutic methods for locally recurrent, metastatic, or progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer. However, multitargeted tyrosine kinase inhibitors (TKIs) such as lenvatinib or sorafenib have been approved for patients with RAI-refractory differentiated thyroid cancer as a second targeted therapy, and these agents can prolong patient survival. However, several cases have been reported that TKIs have caused fatal complications such as fistula formation or bleeding...
January 14, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28079142/the-prognostic-role-of-egfr-tkis-for-patients-with-advanced-non-small-cell-lung-cancer
#11
Dan Zhao, Xuejing Chen, Na Qin, Dan Su, Lijuan Zhou, Quan Zhang, Xi Li, Xinyong Zhang, Mulan Jin, Jinghui Wang
Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078078/radiotherapy-in-the-management-of-gist-state-of-the-art-and-new-potential-scenarios
#12
L Gatto, M Nannini, M Saponara, V Di Scioscio, G Beltramo, G P Frezza, G Ercolani, A D Pinna, A Astolfi, M Urbini, G Brandi, G Biasco, M A Pantaleo
BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. The main treatment for localized gastrointestinal stromal tumors is surgical resection. Unresectable or advanced GIST are poorly responsive to conventional cytotoxic chemotherapy but the introduction of tyrosine kinase inhibitors (TKIs) marked a revolutionary step in the treatment of these patients, radically improving prognosis and clinical benefit. Historically GIST has been considered radiation-resistant, and the role of radiotherapy in the management of patients with GIST is currently restricted to symptomatic palliation in current treatment guidelines...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28075527/recent-development-of-the-second-and-third-generation-irreversible-egfr-inhibitors
#13
REVIEW
Weiwei Han, Yongli Du
Recent reports suggested that essential directions for new lung cancer, breast carcinoma therapies, as well as the roomier realm of targeted cancer therapies were provided through targeting the epidermal growth factor receptor (EGFR). Patients who carrying non-small cell lung carcinoma (NSCLC) with activating mutations in EGFR initially respond well to the EGFR inhibitors erlotinib and gefitinib, which were located the active site of the EGFR kinase and designed to act as competitive inhibitors of combining with the ATP...
January 11, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28074321/predictive-factors-of-early-distant-brain-failure-after-gamma-knife-radiosurgery-alone-in-patients-with-brain-metastases-of-non-small-cell-lung-cancer
#14
Young Cheol Na, Hyun Ho Jung, Hye Ryun Kim, Byoung Chul Cho, Jin Woo Chang, Yong Gou Park, Won Seok Chang
The objective of this study was to elucidate the predictive factors for early distant brain failure in patients with brain metastases of non-small-cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKRS) without previous whole-brain radiotherapy (WBRT) or surgery. We retrospectively reviewed clinical and imaging data of 459 patients with brain metastases of NSCLC who underwent GKRS from June 2008 to December 2013. The primary end-point was early distant brain failure, defined as the detection of newly developed metastatic lesions on magnetic resonance imaging (MRI) 3 months after GKRS...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28073786/phase-1-study-of-twice-weekly-pulse-dose-and-daily-low-dose-erlotinib-as-initial-treatment-for-patients-with-egfr-mutant-lung-cancers
#15
H A Yu, C Sima, D Feldman, L L Liu, B Vaitheesvaran, J Cross, C M Rudin, M G Kris, W Pao, F Michor, G J Riely
BACKGROUND: Patients with EGFR-mutant lung cancers treated with EGFR tyrosine kinase inhibitors (TKIs) develop clinical resistance, most commonly with acquisition of EGFR T790M. Evolutionary modeling suggests that a schedule of twice weekly pulse and daily low-dose erlotinib may delay emergence of EGFR T790M. Pulse dose erlotinib has superior central nervous system (CNS) penetration and may result in superior CNS disease control. METHODS: We evaluated toxicity, pharmacokinetics, and efficacy of twice weekly pulse and daily low-dose erlotinib...
October 25, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28068878/long-term-control-of-hypercortisolism-by-vandetanib-in-a-medullary-thyroid-carcinoma-with-a-somatic-ret-mutation
#16
Anne-Cécile Paepegaey, Beatrix Cochand-Priollet, Estelle Louiset, Pierre Olivier Sarfati, Marco Alifano, Nelly Burnichon, Marie Bienvenu-Perrard, Najiba Lahlou, Léopoldine Bricaire, Lionel Groussin
CONTEXT: Medullary thyroid carcinomas (MTCs) complicated by ectopic Cushing's syndrome have a poor prognosis, partially due to the difficulties to control hypercortisolism by adrenal blocking drugs. Recent reports (including the initial follow-up of this patient) have suggested that tyrosine kinase inhibitors (TKIs) may be a therapeutic option due to an antisecretory action on ACTH. However, there is a lack of long-term follow-up studies. CASE DESCRIPTION: We report the case of a 58 year-old man with a MTC-related Cushing's syndrome resistant to a combination of several anticortisolic drugs...
January 9, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28066597/the-impact-of-smoking-status-on-radiologic-tumor-progression-patterns-and-response-to-epidermal-growth-factor-receptor-egfr-tyrosine-kinase-inhibitors-in-lung-adenocarcinoma-with-activating-egfr-mutations
#17
Yoon Ki Cha, Ho Yun Lee, Myung-Ju Ahn, Keunchil Park, Jin Seok Ahn, Jong-Mu Sun, Yoon-La Choi, Kyung Soo Lee
BACKGROUND: The aim of this study was to evaluate the impact of smoking on the treatment outcome of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant lung adenocarcinoma, with consideration of other factors including radiologic tumor progression pattern according to patient smoking status. METHODS: A total of 224 patients with EGFR mutant lung adenocarcinomas that were treated with EGFR-TKIs were retrospectively reviewed...
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28061471/transformation-to-small-cell-carcinoma-as-an-acquired-resistance-mechanism-to-azd9291-a-case-report
#18
Lin Li, Hui Wang, Chao Li, Zheng Wang, Ping Zhang, Xu Yan
AZD9291, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), benefits patients with T790M mutant non-small-cell lung cancer who fail treatment with first-generation EGFR TKIs. Acquisition of resistance to AZD9291 occurs inevitable and mechanisms need to be explored. We reported an advanced lung adenocarcinoma female with EGFR exon19 deletion treated on AZD9291 after failure of erlotinib and chemotherapy. Disease progressed again after 6 months' treatment of AZD9291 with hepatic metastasis...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28061461/estimation-of-cell-free-circulating-egfr-mutation-concentration-predicts-outcomes-in-nsclc-patients-treated-with-egfr-tkis
#19
Yan-Juan Zhu, Hai-Bo Zhang, Yi-Hong Liu, Fu-Li Zhang, Ya-Zhen Zhu, Yong Li, Jian-Ping Bai, Li-Rong Liu, Yan-Chun Qu, Xin Qu, Xian Chen, Yan Li, Guang-Juan Zheng
Detection of circulating tumor DNA using droplet digital polymerase chain reaction (ddPCR) is a highly-sensitive, minimally invasive alternative to serial biopsies for assessment and management of cancer. We used ddPCR to assess the utility of measuring plasma concentrations of common epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, and T790M) in 57 non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). High baseline plasma EGFR mutation (pEGFRmut) concentrations were associated with shorter progression-free survival (8...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059038/toxicities-of-receptor-tyrosine-kinase-inhibitors-in-cancer-pharmacotherapy-management-with-clinical-pharmacology
#20
Ken-Ichi Fujita, Hiroo Ishida, Yutaro Kubota, Yasutsuna Sasaki
A number of molecularly targeted anticancer drugs that efficiently inhibit receptor tyrosine kinases, so-called receptor tyrosine kinase inhibitors (TKIs), have been developed. Although these receptor TKIs are generally well tolerated, unexpected toxicities sometimes occur in various organs. TKI-induced adverse events not only lower the quality of life of cancer patients but also reduce dose intensity, and sometimes result in treatment discontinuation. To reduce adverse drug events and increase treatment efficacy, oncologists and clinical pharmacologists have made efforts to establish strategies to treat patients via optimal selection and dosing of TKIs...
January 5, 2017: Current Drug Metabolism
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