scholarly journals Fighting tubulin-targeting anticancer drug toxicity and resistance

2017 ◽  
Vol 24 (9) ◽  
pp. T107-T117 ◽  
Author(s):  
Roberta Visconti ◽  
Domenico Grieco
Keyword(s):  
Drug Toxicity ◽  
Kinase Activity ◽  
Triple Negative ◽  
Molecular Targets ◽  
Vinca Alkaloids ◽  
Drug Resistant ◽  
Castration Resistant Prostate Cancer ◽  
Mitotic Progression ◽  
Castration Resistant

Tubulin-targeting drugs, like taxanes and vinca alkaloids, are among the most effective anticancer therapeutics used in the clinic today. Specifically, anti-microtubule cancer drugs (AMCDs) have proven to be effective in the treatment of castration-resistant prostate cancer and triple-negative breast cancer. AMCDs, however, have limiting toxicities that include neutropenia and neurotoxicity, and, in addition, tumor cells can become resistant to the drugs after long-term use. Co-targeting mitotic progression/slippage with inhibition of the protein kinases WEE1 and MYT1 that regulate CDK1 kinase activity may improve AMCD efficacy, reducing the acquisition of resistance by the tumor and side effects from the drug and/or its vehicle. Other possible treatments that improve outcomes in the clinic for these two drug-resistant cancers, including new formulations of the AMCDs and pursuing different molecular targets, will be discussed.

Long-Term Androgen Ablation and Docetaxel Up-Regulate Phosphorylated Akt in Castration Resistant Prostate Cancer

2011 ◽  
Vol 185 (6) ◽  
pp. 2376-2381 ◽  
Author(s):  
Takeo Kosaka ◽  
Akira Miyajima ◽  
Suguru Shirotake ◽  
Eriko Suzuki ◽  
Eiji Kikuchi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Ablation ◽  
Castration Resistant ◽  
Phosphorylated Akt

Patient (pt) characteristics and treatment patterns in the radium (Ra)-223 REASSURE observational study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5042-5042 ◽  
Author(s):  
Celestia S. Higano ◽  
Shawn H. Zimberg ◽  
Sabina Dizdarevic ◽  
Lauren Christine Harshman ◽  
John Logue ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Interim Analysis ◽  
Routine Clinical Practice ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Observation Methods ◽  
Short And Long Term ◽  
Grade 3

5042 Background: Ra-223, a targeted alpha therapy, prolonged survival with good safety in metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 ALSYMPCA trial. REASSURE will evaluate Ra-223 short- and long-term safety in routine clinical practice settings. This is the first planned interim analysis (median 7 mo observation). Methods: This global, prospective, single-arm, observational study enrolled pts with mCRPC with bone metastases (mets) for whom Ra-223 therapy was planned. Follow-up will continue up to 7 years after last Ra-223 dose. Results: 1106 pts (437 N. America, 665 Europe, 4 not recorded) enrolled from 2 Sep 2014 to 22 Sep 2016. Baseline data are available from 583 pts receiving 1st- (1L), 2nd- (2L), or ≥3rd-line (≥3L) Ra-223 for mCRPC(Table). The majority of pts (n=369, 63%) completed 5–6 doses (1L, 70%; 2L, 64%; ≥3L, 49%); median 6 doses (1L,6; 2L, 6; ≥3L, 4). Treatment-emergent drug-related AEs occurred in 215 pts (37%). Post-treatment grade 3/4 thrombocytopenia occurred in 14 pts (2.4%) and anemia in 45 (7.7%). Conclusions: In routine clinical practice, Ra-223 was associated with no short-term safety concerns and appeared to be used in pts with less advanced mCRPC than in ALSYMPCA. The majority of pts on 1L/2L Ra-223 therapy received 5–6 doses. Ra-223 was often used with abiraterone or enzalutamide, but not chemotherapy. The next interim analysis in 2019 will report long-term safety and outcomes on all pts. Clinical trial information: NCT02141438. [Table: see text]

Long-term outcomes of definitive external-beam radiotherapy for non-metastatic castration-resistant prostate cancer

2018 ◽  
Vol 23 (4) ◽  
pp. 749-756 ◽  
Author(s):  
Rihito Aizawa ◽  
Kenji Takayama ◽  
Kiyonao Nakamura ◽  
Takahiro Inoue ◽  
Takashi Kobayashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
External Beam Radiotherapy ◽  
External Beam ◽  
Castration Resistant Prostate Cancer ◽  
Long Term Outcomes ◽  
Castration Resistant
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