Growth inhibitors pre-clinical and clinical evaluation in cancer

conference documentation : Wadham College, Oxford, 1989.

Publisher: IBCTechnical Services in London

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  The widespread adoption of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for the first‐line treatment of patients with advanced EGFR‐mutated non‐small cell lung cancer has resulted in acquired tyrosine kinase inhibitor resistance becoming a ubiquitous clinical . Background: Secreted and transmembrane proteins play key roles in malignant transformation and growth, including in autocrine growth factor expression, receptor oncogene signaling, and immune .   The role of RTKs inhibitors (TKIs) and the intracellular signaling pathways involved, small molecules under clinical trials, and the updates were discussed. We have also compiled information on the outcomes from the various endothelial growth factor receptor (EGFR)–TKIs-based nanoformulations from the preclinical and clinical .   e Background: We have previously shown that protein phosphatase 2A (PP2A) may mediate acquired lapatinib resistance and inhibition of PP2A with okadaic acid enhances lapatinib response in vitro. The aim of this study was to examine the pre-clinical efficacy of LB, a PP2A inhibitor, which has recently completed phase I clinical .

Despite that the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer. Figure 1. In vivo antitumor efficacy of MEK inhibitor RO in multiple human xenograft tumor models including melanoma, colorectal, lung, and pancreatic cancers. Human cancer cells were . The epidermal growth factor receptor (EGFR) is associated with aggressive phenotypes and is an independent predictor of stage progression and mortality in bladder cancer. Gefitinib (‘Iressa,’ ZD) is an orally active EGFR-tyrosine kinase inhibitor. The objective of this study was to evaluate the in vitro and in vivo effects of gefitinib in the EGFR-expressing human bladder cancer .   In preclinical studies, exposure to ZD inhibited the growth of a wide range of cancer cell lines that overexpress EGFR (, , ). Mechanistically, ZD treatment was .

  Stenoparib is currently being evaluated for the treatment of advanced ovarian cancer in a DRP®-guided Phase 2 clinical trial at the Dana-Farber Cancer Institute (Boston, MA U.S.A.) using a .   Revolution Medicines is a clinical-stage oncology company focused on developing novel targeted therapies to inhibit elusive high-value frontier cancer targets within notorious growth and . Other promising pre-clinical observations included a synergistic effect with the antimitotic drug docetaxel in breast cancer [98], colorectal cancer [99], and metastatic pancreatic cancer [ The research efforts have led to the discovery of AMG , the first KRAS G12C inhibitor in clinical development. On 30 October , the investigators published in the Nature an article about itspreclinical evidence and furthermore, reported that in clinical .

Growth inhibitors pre-clinical and clinical evaluation in cancer Download PDF EPUB FB2

EGFR Inhibitors - an overview | ScienceDirect Topics. Preclinical Evaluation of MET Inhibitor INC With or Without the Epidermal Growth Factor Receptor Inhibitor Erlotinib in Non-Small-Cell Lung Cancer Clin Lung Cancer.

May;18(3) Cited by: Here, we describe the preclinical development of G1T28, a novel potent and selective CDK4/6 inhibitor that transiently and reversibly regulates the proliferation of murine and canine bone marrow Cited by: Background: The purpose of this study was to evaluate the activity of Selective Inhibitors of Nuclear Export (SINE) compounds that inhibit the function of the nuclear export protein Exportin 1 (XPO1/CRM1) against canine tumor cell lines and perform a Phase I clinical trial of KPT in dogs with spontaneous cancer Cited by:   In vivo pre-clinical testing of PARP inhibitors as enhancers of anti-cancer agents has been hampered by a lack of potency and specificity of first and second generation compounds and most initial studies assessed the efficacy of chemotherapy in combination with PARP inhibitors.

62 The published data relating to PARP inhibitors Cited by: Pre-clinical data suggest that PARP inhibitors may potentiate the effects of radiotherapy in several tumour types, namely lung, colorectal, head and neck, glioma, cervix and prostate cancers.

In vitro, PARP inhibitors. Purpose: Fibroblast growth factor receptor 1 (FGFR1) and FGFR2 amplifications are observed in approximately 10% of breast cancers and are related to poor outcomes.

We evaluated whether dovitinib (TKI), an inhibitor of FGFR1, FGFR2, and FGFR3, presented antitumor activity in FGFR -amplified breast cancers. Experimental Design: Preclinical.

Preclinical Evaluation of Ureidosulfamate Carbonic Anhydrase IX/XII Inhibitors in the Treatment of Cancers Ureidobenzenesulfonamide CAIX/XII Inhibitors in Preclinical and Clinical Studies. for several reasons. Both cell lines are highly metastatic, which allows study of the effectiveness of CAIX/XII inhibitors on localised cancer growth.

The results of the study published today confirm that T had superior efficacy to a non-targeted pan-PI3K inhibitor alone in a pre-clinical xenograft model, and that the tumor targeting. DNA double-strand breaks (DSB) are the most cytotoxic lesions induced by ionizing radiation and topoisomerase II poisons, such as etoposide and doxorubicin.

A major pathway for the repair of DSB is nonhomologous end joining, which requires DNA-dependent protein kinase (DNA-PK) activity. We investigated the therapeutic use of a potent, specific DNA-PK inhibitor (NU) in models of human cancer. BET inhibitors disrupt this interaction and, through several preclinical studies, were shown to halt transcription of oncogenes, decrease cancer cell survival and induce apoptosis.

Many trials are ongoing to further characterize the relevance of BET inhibitor use in a clinical. Pre-clinical evaluation of AZD, a novel mTORC1/2 dual inhibitor, against renal cell carcinoma and its activity could be further enhanced by the autophagy inhibitor 3-MA. The growth. The purpose of this review is to discuss the current understanding of the Tie2-angiopoietin system and its role in tumor growth and metastasis.

This review also focuses on preclinical and clinical data published to date that have evaluated Tie2-angiopoietin inhibition. Tie2 inhibition has shown significant promise in preclinical. ABP is a novel and potent multi-TRK Inhibitor for several PC-related prime tyrosine kinases (TRKs), such as EGFR, HER2, ALK, and BTK.

Pre-clinical studies with ABP, especially study to evaluate its tumor growth. Pre-clinical studies and clinical evidence from the analysis of a patient with advanced endometrial cancer suggests that tumours with loss of PTEN expression, a recurrent aberration in OCCC [6, 7], may be sensitive to PARP inhibitors.

An evaluation of the effects of bortezomib in murine xenograft models of both lung and breast cancer was also conducted [].Treatment with oral bortezomib mg/kg daily for 18 days caused tumor growth delays, as well as a decrease in the number of metastases in the Lewis lung cancer.

Preclinical and clinical data support cetuximab combinations with a wide variety of chemotherapeutic agents 26 and radiation However, because of the disappointing final data from 2 studies (Iressa Survival Evaluation in Lung Cancer Ruth He, John L.

Marshall, Epidermal Growth Factor Inhibitors, Encyclopedia of Cancer. Looking back at the short but eventful history of this drug class, this book chapter intends to do an evaluation on clinical efficacy and effectiveness of TKIs, basing on the currently available clinical trial data.

Significant limitations of TKIs on cancer treatment. A rationale emerged to support the combination of mTOR antagonists with either tamoxifen or an aromatase inhibitor in pre-clinical models of ER-positive hormone-sensitive and resistant breast cancer.

The estrogen-dependent growth of both wild-type MCF-7 and aromatase-expressing (MCF-7/Aro) breast cancer. The preclinical findings of PARP1 in mediating transcriptional regulation by AR and the ETS fusion protein [20–23] and the potential preclinical synergy of targeting of the PARP and AR pathways provide a strong rationale for the clinical evaluation.

Conclusions: Taken together, these data indicate that RXC is a potent inhibitor of tumour growth in RNF43 loss of function preclinical cancer models. RXC will be evaluated in a first in human Phase 1 study in Phase 1a aims are to characterise the safety profile and PK/PD relationship in cancer.

A series of substituted 4-(4-fluoro-1H-indolyloxy)pyrrolo[2,1-f][1,2,4]triazine-based inhibitors of vascular endothelial growth factor receptor-2 kinase is reported. Structure−activity relationship. Keywords: HDAC inhibitors, BRD4, Jumonji demethylases, Jumonji inhibitors, EZH2 inhibitors, pre-clinical studies, lung cancer, epigenetic therapeutics Introduction The discovery and characterization.

Geldanamycin-based Hsp90 inhibitors. The first Hsp90 inhibitor to enter clinic was the geldanamycin (GM) derivative allylaminodesmethoxygeldanamycin (AAG) (Figure 1).Initial clinical evaluation.

Mol Cancer Ther. Nov;17(11) doi: /MCT Epub Aug Preclinical Evaluation of Nintedanib, a Triple Angiokinase Inhibitor, in Soft-tissue Sarcoma:. In preclinical studies of cell lines and human tumor xenografts, gefitinib produced growth inhibition in a variety of solid tumor types, including lung, prostate, breast, colon, and ovarian cancers.

Background: Signaling through mTOR and somatostatin pathway is implicated in thyroid cancer development. Method: We evaluated everolimus, an mTOR inhibitor and pasireotide, a multi receptor somatostatin analogue as potential therapy of thyroid cancer.

Our aim was to evaluate the abovementioned inhibitors in a pre-clinical model of embryonal tumors (RT and MB) in regard to their anti-cancer properties and potential for brain exposure. The predicted binding modes of these inhibitors. Request PDF | Pre-clinical evaluation of the AR inhibitor enzalutamide in triple negative breast cancer cells | The androgen receptor (AR) is present in approximately 80% of invasive breast cancer.

Abstract. The importance of the purine de novo pathway in providing DNA precursors for cancer cell growth led to the hypothesis that novel antifolate inhibitors of glycinamide ribonucleotide formyltransferase (GARFT), the first folate-dependent enzyme in this pathway, might have utility in the treatment of cancer.

Inclinical. Correction: Evaluation of the Proteasome Inhibitor MLN in Preclinical Models of Human Cancer - Ap Abstract Consequently, severalgroups are pursuing the development of additional small-molecule proteasome inhibitors .Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment Drugs Today (Barc).

Dec;41(12) doi: /dot  Background: Basal-like breast cancers (BLBC) compose up to 15% of breast cancer (BC) and are usually triple negative characterized by lack of ER, PR, and HER-2 amplification.

In addition, most BRCA1-associated BCs are BLBC and TNBC, expressing basal cytokeratins and EGFR. BLBC is characterized by an aggressive phenotype, high histological grade, and poor clinical .