Cocktail and Poster viewing Poster Display session

14P - Butein inhibits solid tumors cell viability, colony, and tumor growth via STAT3 signaling pathway and enhance the anti-cancer effects of Frondoside-A and camptothecin (ID 190)

Presentation Number
14P
Lecture Time
18:25 - 18:25
Speakers
  • S. Attoub
Location
Hall Bordeaux, Palais des Congrès, Paris, France
Date
26.02.2019
Time
18:00 - 18:45
Authors
  • S. Attoub
  • S. Sulaiman
  • K. Arafat

Abstract

Background

Despite the major recent advances in cancer management, cure of cancer remains a serious challenge.

Methods

In the current study, we investigated the impact of butein, a biologically active flavonoid, on the human cancer cell survival and colony growth in vitro, and on tumor growth in vivo, alone and in combination with Frondoside-A, a triterpenoid glycoside isolated from an Atlantic sea cucumber, and camptothecin.

Results

We demonstrate that butein causes a concentration- and time-dependent decrease in the viability of the lung cancer cells (A549 and LNM35), the breast cancer cells (MDA-MB-231 and T47D), and a decrease in their related colonies growth in vitro. Similarly, treatment with butein significantly decreased the growth of A549 and MDA-MB-231 xenografts in the chick embryo model in vivo (P < 0.01) without significant toxicity. To determine whether the inhibition of cell viability and tumor growth by butein is due to growth arrest or to cell death, we assessed the induction of apoptosis by measuring caspase-3 activity and PARP cleavage. The treatment of lung and breast cancer cells with butein induce caspase-3 activation leading to PARP inactivation in a concentration and time-dependent manner. More than 50% of lung cancers and 40% of breast cancers show constitutive activation of STAT3. The role of this transcription factor in cancer progression is now well established and its targeting in cancer therapy is a very promising and challenging option. We observed that butein treatment induce a concentration and time-dependent inhibition of STAT3 phosphorylation without any impact on total STAT3. We finally demonstrate that butein at the IC25 and IC50 concentration enhances the anti-cancer effect of Frondoside-A as well as the effect of camptothecin on lung and breast cancer cells in vitro.

Conclusions

These findings increase our confidence of the potential benefit of using butein as an anticancer agent for the treatment of solid tumors either alone, and/or in combination with Frondoside-A and camptothecin.

Legal entity responsible for the study

Samir Attoub.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Liquid biopsies as biomarkers for early drug development Educational session

Session DOI (ID 215)

Lecture Time
09:35 - 09:35
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
25.02.2019
Time
09:35 - 11:00
Immune checkpoint inhibitors with targeted agents: Challenging marriages Educational session

PARP and PD-1/PDL1 inhibition (ID 30)

Lecture Time
13:40 - 14:00
Speakers
  • G. Curigliano
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
26.02.2019
Time
13:35 - 15:05
Authors
  • G. Curigliano
Targeting oncogenes generated by gene fusions Educational session

ROS1 and ALK (ID 57)

Lecture Time
14:35 - 14:55
Speakers
  • R. Doebele
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
27.02.2019
Time
13:30 - 15:00
Authors
  • R. Doebele
Selected Poster Presentation Poster Display session

9P - Safety profile and therapeutic efficacy of one cycle of [177Lu]prostate-specific membrane antigen (PSMA) in end stage metastatic castration-resistant prostate cancer patients with low performance status (ID 79)

Presentation Number
9P
Lecture Time
17:40 - 17:45
Speakers
  • M. Gupta
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
26.02.2019
Time
17:30 - 18:00
Authors
  • M. Gupta
  • P. Choudhury
  • S. Rawal
  • H. Goel
  • V. Talwar
  • K. Dutta
  • A. Singh

Abstract

Background

Prostate cancer patients with distant metastasis have poor prognosis and develop resistance to all standard drugs at various time intervals. Therapeutic options which can alleviate symptoms and prolong survival are required for these patients. [177Lu]prostate-specific membrane antigen ([177Lu]PSMA) is a novel drug based on a theranostic concept. Here, we have presented the safety and efficacy profile of one cycle of [177Lu]PSMA in metastatic castration-resistant prostate cancer (mCRPC) patients who have exhausted all standard therapeutic options.

Methods

Twenty two patients treated with at least first line anti-androgens and docetaxel were treated with one cycle of [177Lu]PSMA therapy on a compassionate basis. Haemoglobin, total leukocyte counts, platelets and serum creatinine for toxicity profile while prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, visual analogue scale (VAS) and analgesic quantification scale (AQS) for therapeutic efficacy were recorded pre and 8 weeks post therapy. Wilcoxon signed-rank and ANOVA tests were used for statistical analysis.

Results

Partial response (PR), stable disease (SD) and progressive disease (PD) for PSA were seen in 5 (22.7%), 13 (59.1%) and 4 (18.2%) patients, respectively, treated with mean 6.88GBq dose of [177Lu]PSMA. 8/22 (36.4%) patients showed ≥ 30% drop in PSA. Grade 3 haemoglobin toxicity was seen in 5/22 (22.7%) patients. No patient developed grade 4 haemoglobin toxicity. No patients had grade 3 or 4 leukocytopenia or thrombocytopenia. Wilcoxon signed-rank test showed statistically significant (p < 0.05) difference in pre- and post-treatment ECOG, VAS, AQS scores while it was not significant for PSA (P > 0.05). ANOVA test showed a statistically significant difference in mean doses of [177Lu]PSMA used in the three PSA response groups while the difference was non-significant for other variables.

Conclusions

We conclude that [177Lu]PSMA therapy delivers adequate pain palliation in all end-stage mCRPC patients and it has a potential to become an effective therapeutic option in properly selected patients.

Legal entity responsible for the study

Manoj Gupta.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Opening and welcome + Honorary award Keynote lecture Educational session

Presentation of the TAT 2019 Honorary Award (ID 3)

Lecture Time
08:55 - 09:00
Speakers
  • A. Adjei
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
25.02.2019
Time
08:45 - 09:30
Authors
  • A. Adjei
Immune checkpoint combinations: How to marry rationally Educational session

Preclinical models to assess timing of combination regimens (ID 26)

Lecture Time
09:45 - 10:05
Speakers
  • S. Khleif
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
26.02.2019
Time
09:00 - 10:30
Authors
  • S. Khleif
KRAS Educational session

Inhibiting K-ras in the clinic: The saga continues (ID 50)

Lecture Time
12:05 - 12:25
Speakers
  • A. Adjei
Session Name
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
27.02.2019
Time
11:00 - 12:30
Authors
  • A. Adjei
Selected Poster Presentation Poster Display session

Q&A (ID 212)

Lecture Time
17:45 - 17:50
Speakers
  • J. De Bono
  • E. Calvo
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
26.02.2019
Time
17:30 - 18:00
Authors
  • J. De Bono
  • E. Calvo
Cocktail and Poster viewing Poster Display session

31P - Comprehensive genomic profiling of Chinese esophageal squamous cell carcinoma patients (ID 141)

Presentation Number
31P
Lecture Time
18:30 - 18:30
Speakers
  • Y. Ji
Location
Hall Bordeaux, Palais des Congrès, Paris, France
Date
26.02.2019
Time
18:00 - 18:45
Authors
  • Y. Ji
  • Y. Wu
  • W. Fu
  • L. Liu
  • Z. Tian
  • S. Wen
  • K. Zhang
  • M. Yao
  • A. Liu
  • Y. Zhou

Abstract

Background

Esophageal squamous cell carcinoma (ESCC) is the most important pathological type of esophageal cancer with high incidence and limited efficient therapies in China and worldwide. Understanding of ESCC genomic features is advantageous for exploring clinical therapeutic strategies.

Methods

Deep sequencing targeting 450 cancer genes was performed on FFPE and matched blood samples collected from 90 Chinese ESCC patients(pts) with a median age of 60 years old. Genomic alterations (GAs) including single nucleotide variations, short and long indel, gene rearrangements and copy number variations were analyzed. Tumor mutation burden (TMB) was assessed in all samples by standard NGS algorithms. The expression of PD-L1 in 44 samples was evaluated by IHC (28-8 Ab).

Results

The most commonly found GAs were mutations in TP53 (94.4%), FGF3 (43.3%), CCND1 (43.3%), FGF4 (42.2%), FGF19 (42.2 %), CDKN2A (36.7%), NOTCH1 (25.6%), PIK3CA (22.2%), and ERBB2 amp(2.2%).Compared with TCGA data, the frequency of TP53 and ERBB2 amp mutations was similar, while the frequency of NOTCH1 mutations was significantly higher (25.6% vs 11%) and the frequency of EGFR amp was lower (5.6% vs 19%) in Chinese cohort. In addition, 4 of 90 samples harbored germline mutations (SDHA, RAD51C, PALB2 and BCL2L11). Among these GAs, 73.3% mutations were in cell cycle (62.2%) and PI3K/AKT (42.2%) pathway. In Chinese ESCC pts, the median TMB was 7.0 muts/Mb, and some pts showed high TMB (33.3%pts≥10 muts/Mb,11.1%pts≥20 muts/Mb). 15.6% pts (TMB≥10 muts/Mb) harbored chromosome 11q13 (FGF3/4/19 and CCND1) amp, which may be related to immunotherapy hyper-progression. Based on the IHC analysis, 10 of 44 Chinese pts showed positive (TPS≥1%) PD-L1 expression, and 7 of them also showed high TMB (≥10 muts /Mb). However, no correlation was found between high TMB and PD-L1 expression.

Conclusions

In this study, we found that the frequencies of GAs, such as EGFR and NOTCH1 alterations, were different between Chinese and western ESCC pts. Compared to Western ESCC pts, the positivity of PD-L1 expression was similar, while TMB was higher in Chinese ESCC pts. These findings suggested potential therapeutic targets for targeted and immunotherapies of Chinese ESCC pts.

Legal entity responsible for the study

OrigiMed.

Funding

Has not received any funding.

Disclosure

M. Yao, A. Liu, Y. Zhou: Employee: OrigiMed. All other authors have declared no conflicts of interest.

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Learning from haemato-oncology trials Educational session

Epigenetic dysregulation in hematological malignancies (ID 18)

Lecture Time
15:50 - 16:10
Speakers
  • O. Bernard
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
25.02.2019
Time
15:45 - 17:15
Authors
  • O. Bernard
Monotherapy vulnerability- Cell cycle checkpoint and DNA damage/repair inhibitors Educational session

Introduction (ID 41)

Lecture Time
09:00 - 09:05
Speakers
  • G. Shapiro
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
27.02.2019
Time
09:00 - 10:30
Authors
  • G. Shapiro