Nanotechnologies light up the antitumor potency by combining chemotherapy with siRNA

2021 ◽  
Author(s):  
Jian Sun ◽  
Edikan Archibong Ogunnaike ◽  
Xing Jiang ◽  
Zhaowei Chen
Keyword(s):  
Single Agent ◽  
Anticancer Therapy ◽  
Considerable Promise ◽  
Novel Approaches

Nanotechnology-based combination anticancer therapy offers novel approaches to overcome the limitations of single-agent administration. The emerging siRNA technology combined with chemotherapy has shown considerable promise in anticancer therapy. There are...

Randomized, Double-Blind, Placebo-Controlled Phase II Study of Single-Agent Oral Talactoferrin in Patients With Locally Advanced or Metastatic Non–Small-Cell Lung Cancer That Progressed After Chemotherapy

2011 ◽  
Vol 29 (31) ◽  
pp. 4129-4136 ◽  
Author(s):  
Purvish M. Parikh ◽  
Ashok Vaid ◽  
Suresh H. Advani ◽  
Raghunadharao Digumarti ◽  
Jayaprakash Madhavan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Patient Population ◽  
Single Agent ◽  
Locally Advanced ◽  
Anticancer Therapy ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung

Purpose To investigate the activity and safety of oral talactoferrin (TLF) in patients with stages IIIB to IV non–small-cell lung cancer (NSCLC) for whom one or two prior lines of systemic anticancer therapy had failed. Patients and Methods Patients (n = 100) were randomly assigned to receive either oral TLF (1.5 g in 15 mL phosphate-based buffer) or placebo (15 mL phosphate-based buffer) twice per day in addition to supportive care. Oral TLF or placebo was administered for a maximum of three 14-week cycles with dosing for 12 consecutive weeks followed by 2 weeks off. The primary objective was overall survival (OS) in the intent-to-treat (ITT) patient population. Secondary objectives included progression-free survival (PFS), disease control rate (DCR), and safety. Results TLF was associated with improvement in OS in the ITT patient population, meeting the protocol-specified level of significance of a one-tailed P = .05. Compared with the placebo group, median OS increased by 65% in the TLF group (3.7 to 6.1 months; hazard ratio, 0.68; 90% CI, 0.47 to 0.98; P = .04 with one-tailed log-rank test). Supportive trends were also observed for PFS and DCR. TLF was well tolerated and, generally, there were fewer adverse events (AEs) and grade ≥ 3 AEs reported in the TLF arm. AEs were consistent with those expected in late-stage NSCLC. Conclusion TLF demonstrated an apparent improvement in OS in patients with stages IIIB to IV NSCLC for whom one or two prior lines of systemic anticancer therapy had failed and was well tolerated. These results should be confirmed in a global phase III trial.

scholarly journals Targeting BCL2-Proteins for the Treatment of Solid Tumours

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Meike Vogler
Keyword(s):  
Clinical Trials ◽  
Small Molecules ◽  
Single Agent ◽  
Clinical Applications ◽  
Comprehensive Analysis ◽  
Solid Tumours ◽  
Haematological Malignancies ◽  
Novel Approaches

Due to their central role in the regulation of apoptosis, the antiapoptotic BCL2-proteins are highly promising targets for the development of novel anticancer treatments. To this end, several strategies have been developed to inhibit BCL2,BCL-XL, BCL-w, and MCL1. While early clinical trials in haematological malignancies demonstrated exciting single-agent activity of BCL2-inhibitors, the response in solid tumours was limited, indicating that, in solid tumours, different strategies have to be developed in order to successfully treat patients with BCL2-inhibitors. In this review, the function of the different antiapoptotic BCL2-proteins and their role in solid tumours will be discussed. In addition, a comprehensive analysis of current small molecules targeting these antiapoptotic BCL2-proteins (e.g., ABT-737, ABT-263, ABT-199, TW-37, sabutoclax, obatoclax, and MIM1) will be provided including a discussion of the results of any clinical trials. This analysis will summarise the potential of BCL2-inhibitors for the treatment of solid tumours and will unravel novel approaches to utilise these inhibitors in clinical applications.

scholarly journals DREAMM-8: A Phase III Study of the Efficacy and Safety of Belantamab Mafodotin with Pomalidomide and Dexamethasone (B-Pd) Vs Pomalidomide Plus Bortezomib and Dexamethasone (PVd) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-4
Author(s):  
Suzanne Trudel ◽  
Randy Davis ◽  
Nicole M. Lewis ◽  
Kalpana K. Bakshi ◽  
Bikramjit Chopra ◽  
...  
Keyword(s):  
Disease Progression ◽  
Safety Profile ◽  
Research Funding ◽  
Group Performance ◽  
Single Agent ◽  
Anticancer Therapy ◽  
Prior Exposure ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Publicly Traded

Introduction: Belantamab mafodotin (belamaf; GSK2857916) is a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate. In the pivotal Phase II DREAMM-2 study, single-agent belamaf demonstrated deep and durable responses with a manageable safety profile in heavily pretreated patients with RRMM (Lonial et al. Lancet Oncol 2020). Responses were sustained at 13 months of follow-up; with belamaf (2.5 mg/kg administered intravenously [IV] every 3 weeks [Q3W]), overall response rate (ORR) was 32% and median duration of response (DoR) was 11.0 months (Lonial et al. ASCO 2020 Poster 436). Preclinical data suggest synergistic antimyeloma activity of belamaf in combination with pomalidomide/dexamethasone (Pd). Preliminary data from an ongoing Phase I/II study (NCT03715478) evaluating belamaf in combination with Pd (B-Pd) suggest an acceptable safety profile and early signs of clinical activity in patients with RRMM. The DREAMM-8 study (NCT04484623) will evaluate the efficacy and safety of B-Pd compared with pomalidomide, bortezomib, and dexamethasone (PVd). Methods: This Phase III, two-arm, randomized, open-label, multicenter study will include patients with measurable RRMM who have received ≥1 prior line of therapy (including lenalidomide), with documented disease progression during or after their most recent line of treatment. Patients aged ≥18 years with Eastern Cooperative Oncology Group Performance Status 0-2, adequate organ system function, and who provide informed consent will be eligible. Patients with prior exposure to BCMA-targeted therapies or pomalidomide and those intolerant/refractory to bortezomib will be excluded. Approximately 450 patients will be randomized (1:1) to Arm A (B-Pd) or Arm B (PVd), stratified by number of prior lines of treatment, prior exposure to bortezomib, and International Staging System status. No more than 50% of participants with two or more prior lines of treatment will be enrolled. In Arm A, patients will receive belamaf 2.5 mg/kg (IV) Q4W on Day 1 in Cycle 1 (28-day cycle) followed by belamaf 1.9 mg/kg (IV) Q4W on Day 1 in Cycle 2 onwards (28-day cycles); pomalidomide 4 mg (orally [PO]) will be administered on Days 1-21 and dexamethasone 40 mg (PO) on Days 1, 8, 15, and 22 in all cycles (28-day cycles). In Arm B, pomalidomide 4 mg (PO) will be administered Q3W on Days 1-14 in all cycles (21-day cycles); bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8, and 11 in Cycles 1-8, and Days 1 and 8 in Cycle 9+ (21-day cycles). Dexamethasone 20 mg (PO) will be administered on the day of and the day after bortezomib. The dose level of dexamethasone in each arm will be reduced by half in patients >75 years of age. Treatment in both arms will continue until progressive disease, unacceptable toxicity, withdrawal of consent, initiation of another anticancer therapy, or end of study or death. The primary endpoint is progression-free survival (PFS; time from randomization to the earliest date of documented disease progression or death [any cause]). Minimal residual disease negativity rate is a key secondary endpoint. Additional secondary endpoints include ORR, time to response, DoR, time to progression, overall survival, PFS2 (PFS after initiation of new anticancer therapy), safety, health-related quality of life, and pharmacokinetic and pharmacodynamic parameters. The study is planned to start in August 2020. Funding: GSK (Study 207499); drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. Disclosures Trudel: GSK, Celgene, Janssen, Amgen, Genentech: Research Funding; Celgene, Janssen, Takeda, Sanofi, Karyopharm, Amgen Canada: Honoraria; Celgene, Amgen, GSK: Consultancy, Research Funding. Davis:GSK: Current Employment, Current equity holder in publicly-traded company. Lewis:GSK: Current Employment, Current equity holder in publicly-traded company. Bakshi:GSK: Current Employment, Current equity holder in publicly-traded company. Chopra:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Montes de Oca:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ferron-Brady:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Eliason:GSK: Current Employment, Current equity holder in publicly-traded company. Kremer:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Wu:GSK: Current Employment, Current equity holder in publicly-traded company.

scholarly journals Drugging the Undruggable: Advances on RAS Targeting in Cancer

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 899
Author(s):  
Miriam Molina-Arcas ◽  
Amit Samani ◽  
Julian Downward
Keyword(s):  
Clinical Evidence ◽  
Single Agent ◽  
Biochemical Properties ◽  
Combination Therapies ◽  
Primary Resistance ◽  
Activating Mutations ◽  
High Affinity ◽  
Fda Approval ◽  
Novel Approaches ◽  
Ras Isoforms

Around 20% of all malignancies harbour activating mutations in RAS isoforms. Despite this, there is a deficiency of RAS-targeting agents licensed for therapeutic use. The picomolar affinity of RAS for GTP, and the lack of suitable pockets for high-affinity small-molecule binding, precluded effective therapies despite decades of research. Recently, characterisation of the biochemical properties of KRAS-G12C along with discovery of its ‘switch-II pocket’ have allowed development of effective mutant-specific inhibitors. Currently seven KRAS-G12C inhibitors are in clinical trials and sotorasib has become the first one to be granted FDA approval. Here, we discuss historical efforts to target RAS directly and approaches to target RAS effector signalling, including combinations that overcome limitations of single-agent targeting. We also review pre-clinical and clinical evidence for the efficacy of KRAS-G12C inhibitor monotherapy followed by an illustration of combination therapies designed to overcome primary resistance and extend durability of response. Finally, we briefly discuss novel approaches to targeting non-G12C mutant isoforms.

scholarly journals Preclinical Evaluation of the WEE1 Inhibitor MK-1775 as Single-Agent Anticancer Therapy

2013 ◽  
Vol 12 (8) ◽  
pp. 1442-1452 ◽  
Author(s):  
Amy D. Guertin ◽  
Jing Li ◽  
Yaping Liu ◽  
Melissa S. Hurd ◽  
Alwin G. Schuller ◽  
...  
Keyword(s):  
Single Agent ◽  
Anticancer Therapy ◽  
Preclinical Evaluation

Novel Approaches to Low-Voltage Scanning Electron Microscopy

1990 ◽  
Vol 48 (1) ◽  
pp. 366-367
Author(s):  
Arthur V. Jones
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Low Voltage ◽  
Electron Optics ◽  
Current Interest ◽  
New Concepts ◽  
Opportune Time ◽  
Novel Approaches ◽  
Voltage Scanning ◽  
Scanning Electron

In comparison with the developers of other forms of instrumentation, scanning electron microscope manufacturers are among the most conservative of people. New concepts usually must wait many years before being exploited commercially. The field emission gun, developed by Albert Crewe and his coworkers in 1968 is only now becoming widely available in commercial instruments, while the innovative lens designs of Mulvey are still waiting to be commercially exploited. The associated electronics is still in general based on operating procedures which have changed little since the original microscopes of Oatley and his co-workers.The current interest in low-voltage scanning electron microscopy will, if sub-nanometer resolution is to be obtained in a useable instrument, lead to fundamental changes in the design of the electron optics. Perhaps this is an opportune time to consider other fundamental changes in scanning electron microscopy instrumentation.

Sign in / Sign up

Export Citation Format

Share Document