Gustave Roussy Cancer Center

Villejuif, France

Gustave Roussy Cancer Center

Villejuif, France
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News Article | May 23, 2017
Site: globenewswire.com

INNATE PHARMA TO HOLD ITS ANNUAL GENERAL MEETING OF SHAREHOLDERS ON JUNE 23, 2017 Innate Pharma (the "Company" - Euronext Paris: FR0010331421 - IPH) will hold its Annual General Meeting of Shareholders ("AGM") on June 23, 2017, at 10:00 am in its headquarters, 117 avenue de Luminy, F-13009 Marseille. The Notice of Meeting of this Shareholders' Meeting was published on May 19, 2017, in the French official legal bulletin ("BALO"). It includes the agenda, the proposed resolutions as well as instructions to participate and vote in this Meeting. It is also available . All documentation regarding this AGM will be made available to shareholders in accordance with existing regulations and will be available on the Company's website as of today . Among the resolutions, the following will be proposed during the AGM: Professor Jean-Charles Soria will replace Professor Michael Caligiuri, who has been named American Association for Cancer Research (AACR) President and resigned from the Supervisory board. Hervé Brailly, Chairman of the Supervisory board, commented: "On behalf of all Supervisory board members, I would like to express our deepest gratitude to Professor Caligiuri, who has just been named President of AACR, one of the most prestigious worldwide cancer associations, for his commitment to the Board during the four years of his mandate. His medical expertise and experience have been valuable assets to the Board. We propose the appointment of Professor Jean-Charles Soria to succeed him. Professor Jean-Charles Soria is an oncologist, Head of Drug Development department at Gustave Roussy cancer center, and a renowned world leader in the field of immuno-oncology. We are also pleased to propose the appointment of Bpifrance Participations, represented by Maïlys Ferrère. Bpifrance Participations holds Innate Pharma's shares since 2009 and has supported the Company ever since. This appointment of Bpifrance Participations as member of the Supervisory board shows once again their commitment to Innate Pharma. These proposals guarantee the wealth, diversity and complementarity of profiles which composed the Board and we will pursue our work thanks to the expertise of each of its members." Maïlys Ferrère is Director of the Large Venture Investment Pole within the Innovation Division of Bpifrance. Large Venture's mission is to provide long term capital to innovative French companies in areas with very strong growth with the goal of creating world leaders. The portfolio currently includes thirty companies in life sciences, digital and environmental technologies. Prior to this position, Maïlys Ferrère was an Investment Director at the Strategic Investment Fund between 2009 and 2012. She previously had a career in banking, specialized in equity capital markets in various financial institutions. Maïlys Ferrère is a member of the Boards of Directors or Supervisory boards of the following companies: DBV, Valneva SE, Pixium, Gensight and Euronext Paris. Professor Jean-Charles Soria is a medical oncologist and a Professor of Medicine and Medical Oncology at South-Paris University. He is a full-time cancer specialist at Institut Gustave Roussy. Professor Soria trained as a medical oncologist and obtained the Silver medal from Paris Medical School in 1997. He gained a postgraduate degree and a PhD degree in molecular biology (fundamental basis of oncogenesis) in 2001, and completed his training with a two-year post-doctoral fellowship at MD Anderson Cancer Center, Houston, USA, where he has held an Adjunct Professorship since 2012. Professor Soria is also a member of the thoracic pathology committee at Gustave Roussy Cancer Center. He is a recognized expert on targeted therapies, immunotherapy and lung cancer. His main research interests are: early clinical development, pharmacodynamic biomarkers, lung cancer, immunotherapy and personalized medicine. He is also involved in translational research aspects related to precision medicine and tumor progression notably in lung cancer models (INSERM unit 981). Only shareholders having registered their shares at least two business days prior to the date of the AGM, by midnight Paris time, will be able to attend. Shareholders holding "au porteur" (bearer) shares will need to obtain an "attestation de participation" (certificate of shareholding) from their brokers. This "attestation de participation" must be attached to the proxy form or to the appropriate voting form if shareholders wish to designate a proxy or vote by post. The "attestation de participation" may replace the admission card for shareholders wishing to attend the AGM in person. Written questions from shareholders must be received from the day of the publication of the official convocation to the AGM up until four business days prior to the AGM (by registered letter, addressed to the registered office, or by e-mail to investors@innate-pharma.com). Shareholders may obtain the legal documentation in preparation of the AGM (as described in article R. 225-83 of the French "Code de Commerce") by sending a request: Innate Pharma S.A. is a clinical-stage biotechnology company with a focus on discovering and developing first-in-class therapeutic antibodies that harness the innate immune system to improve cancer treatment and clinical outcomes for patients. Innate Pharma specializes in immuno-oncology, a new therapeutic field that is changing cancer treatment by mobilizing the power of the body's immune system to recognize and kill cancer cells. The Company's aim is to become a fully-integrated biopharmaceutical company in the area of immunotherapy and focused on serious unmet medical needs in cancer. Innate Pharma has pioneered the discovery and development of checkpoint inhibitors to activate the innate immune system. Innate Pharma's innovative approach has resulted in three first-in-class, clinical-stage antibodies targeting natural killer cell receptors that may address a broad range of solid and hematological cancer indications as well as additional preclinical product candidates and technologies. Targeting receptors involved in innate immunity also creates opportunities for the Company to develop therapies for inflammatory diseases. The Company's expertise and understanding of natural killer cell biology have enabled it to enter into major alliances with leaders in the biopharmaceutical industry including AstraZeneca, Bristol-Myers Squibb and Sanofi. Based in Marseille, France, Innate Pharma has more than 170 employees and is listed on Euronext Paris. Learn more about Innate Pharma at www.innate-pharma.com. This press release contains certain forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. For a discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Document de Reference prospectus filed with the AMF, which is available on the AMF website (http://www.amf-france.org) or on Innate Pharma's website. This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country.


News Article | May 23, 2017
Site: globenewswire.com

INNATE PHARMA TO HOLD ITS ANNUAL GENERAL MEETING OF SHAREHOLDERS ON JUNE 23, 2017 Innate Pharma (the "Company" - Euronext Paris: FR0010331421 - IPH) will hold its Annual General Meeting of Shareholders ("AGM") on June 23, 2017, at 10:00 am in its headquarters, 117 avenue de Luminy, F-13009 Marseille. The Notice of Meeting of this Shareholders' Meeting was published on May 19, 2017, in the French official legal bulletin ("BALO"). It includes the agenda, the proposed resolutions as well as instructions to participate and vote in this Meeting. It is also available . All documentation regarding this AGM will be made available to shareholders in accordance with existing regulations and will be available on the Company's website as of today . Among the resolutions, the following will be proposed during the AGM: Professor Jean-Charles Soria will replace Professor Michael Caligiuri, who has been named American Association for Cancer Research (AACR) President and resigned from the Supervisory board. Hervé Brailly, Chairman of the Supervisory board, commented: "On behalf of all Supervisory board members, I would like to express our deepest gratitude to Professor Caligiuri, who has just been named President of AACR, one of the most prestigious worldwide cancer associations, for his commitment to the Board during the four years of his mandate. His medical expertise and experience have been valuable assets to the Board. We propose the appointment of Professor Jean-Charles Soria to succeed him. Professor Jean-Charles Soria is an oncologist, Head of Drug Development department at Gustave Roussy cancer center, and a renowned world leader in the field of immuno-oncology. We are also pleased to propose the appointment of Bpifrance Participations, represented by Maïlys Ferrère. Bpifrance Participations holds Innate Pharma's shares since 2009 and has supported the Company ever since. This appointment of Bpifrance Participations as member of the Supervisory board shows once again their commitment to Innate Pharma. These proposals guarantee the wealth, diversity and complementarity of profiles which composed the Board and we will pursue our work thanks to the expertise of each of its members." Maïlys Ferrère is Director of the Large Venture Investment Pole within the Innovation Division of Bpifrance. Large Venture's mission is to provide long term capital to innovative French companies in areas with very strong growth with the goal of creating world leaders. The portfolio currently includes thirty companies in life sciences, digital and environmental technologies. Prior to this position, Maïlys Ferrère was an Investment Director at the Strategic Investment Fund between 2009 and 2012. She previously had a career in banking, specialized in equity capital markets in various financial institutions. Maïlys Ferrère is a member of the Boards of Directors or Supervisory boards of the following companies: DBV, Valneva SE, Pixium, Gensight and Euronext Paris. Professor Jean-Charles Soria is a medical oncologist and a Professor of Medicine and Medical Oncology at South-Paris University. He is a full-time cancer specialist at Institut Gustave Roussy. Professor Soria trained as a medical oncologist and obtained the Silver medal from Paris Medical School in 1997. He gained a postgraduate degree and a PhD degree in molecular biology (fundamental basis of oncogenesis) in 2001, and completed his training with a two-year post-doctoral fellowship at MD Anderson Cancer Center, Houston, USA, where he has held an Adjunct Professorship since 2012. Professor Soria is also a member of the thoracic pathology committee at Gustave Roussy Cancer Center. He is a recognized expert on targeted therapies, immunotherapy and lung cancer. His main research interests are: early clinical development, pharmacodynamic biomarkers, lung cancer, immunotherapy and personalized medicine. He is also involved in translational research aspects related to precision medicine and tumor progression notably in lung cancer models (INSERM unit 981). Only shareholders having registered their shares at least two business days prior to the date of the AGM, by midnight Paris time, will be able to attend. Shareholders holding "au porteur" (bearer) shares will need to obtain an "attestation de participation" (certificate of shareholding) from their brokers. This "attestation de participation" must be attached to the proxy form or to the appropriate voting form if shareholders wish to designate a proxy or vote by post. The "attestation de participation" may replace the admission card for shareholders wishing to attend the AGM in person. Written questions from shareholders must be received from the day of the publication of the official convocation to the AGM up until four business days prior to the AGM (by registered letter, addressed to the registered office, or by e-mail to investors@innate-pharma.com). Shareholders may obtain the legal documentation in preparation of the AGM (as described in article R. 225-83 of the French "Code de Commerce") by sending a request: Innate Pharma S.A. is a clinical-stage biotechnology company with a focus on discovering and developing first-in-class therapeutic antibodies that harness the innate immune system to improve cancer treatment and clinical outcomes for patients. Innate Pharma specializes in immuno-oncology, a new therapeutic field that is changing cancer treatment by mobilizing the power of the body's immune system to recognize and kill cancer cells. The Company's aim is to become a fully-integrated biopharmaceutical company in the area of immunotherapy and focused on serious unmet medical needs in cancer. Innate Pharma has pioneered the discovery and development of checkpoint inhibitors to activate the innate immune system. Innate Pharma's innovative approach has resulted in three first-in-class, clinical-stage antibodies targeting natural killer cell receptors that may address a broad range of solid and hematological cancer indications as well as additional preclinical product candidates and technologies. Targeting receptors involved in innate immunity also creates opportunities for the Company to develop therapies for inflammatory diseases. The Company's expertise and understanding of natural killer cell biology have enabled it to enter into major alliances with leaders in the biopharmaceutical industry including AstraZeneca, Bristol-Myers Squibb and Sanofi. Based in Marseille, France, Innate Pharma has more than 170 employees and is listed on Euronext Paris. Learn more about Innate Pharma at www.innate-pharma.com. This press release contains certain forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. For a discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Document de Reference prospectus filed with the AMF, which is available on the AMF website (http://www.amf-france.org) or on Innate Pharma's website. This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country.


News Article | May 23, 2017
Site: globenewswire.com

INNATE PHARMA TO HOLD ITS ANNUAL GENERAL MEETING OF SHAREHOLDERS ON JUNE 23, 2017 Innate Pharma (the "Company" - Euronext Paris: FR0010331421 - IPH) will hold its Annual General Meeting of Shareholders ("AGM") on June 23, 2017, at 10:00 am in its headquarters, 117 avenue de Luminy, F-13009 Marseille. The Notice of Meeting of this Shareholders' Meeting was published on May 19, 2017, in the French official legal bulletin ("BALO"). It includes the agenda, the proposed resolutions as well as instructions to participate and vote in this Meeting. It is also available . All documentation regarding this AGM will be made available to shareholders in accordance with existing regulations and will be available on the Company's website as of today . Among the resolutions, the following will be proposed during the AGM: Professor Jean-Charles Soria will replace Professor Michael Caligiuri, who has been named American Association for Cancer Research (AACR) President and resigned from the Supervisory board. Hervé Brailly, Chairman of the Supervisory board, commented: "On behalf of all Supervisory board members, I would like to express our deepest gratitude to Professor Caligiuri, who has just been named President of AACR, one of the most prestigious worldwide cancer associations, for his commitment to the Board during the four years of his mandate. His medical expertise and experience have been valuable assets to the Board. We propose the appointment of Professor Jean-Charles Soria to succeed him. Professor Jean-Charles Soria is an oncologist, Head of Drug Development department at Gustave Roussy cancer center, and a renowned world leader in the field of immuno-oncology. We are also pleased to propose the appointment of Bpifrance Participations, represented by Maïlys Ferrère. Bpifrance Participations holds Innate Pharma's shares since 2009 and has supported the Company ever since. This appointment of Bpifrance Participations as member of the Supervisory board shows once again their commitment to Innate Pharma. These proposals guarantee the wealth, diversity and complementarity of profiles which composed the Board and we will pursue our work thanks to the expertise of each of its members." Maïlys Ferrère is Director of the Large Venture Investment Pole within the Innovation Division of Bpifrance. Large Venture's mission is to provide long term capital to innovative French companies in areas with very strong growth with the goal of creating world leaders. The portfolio currently includes thirty companies in life sciences, digital and environmental technologies. Prior to this position, Maïlys Ferrère was an Investment Director at the Strategic Investment Fund between 2009 and 2012. She previously had a career in banking, specialized in equity capital markets in various financial institutions. Maïlys Ferrère is a member of the Boards of Directors or Supervisory boards of the following companies: DBV, Valneva SE, Pixium, Gensight and Euronext Paris. Professor Jean-Charles Soria is a medical oncologist and a Professor of Medicine and Medical Oncology at South-Paris University. He is a full-time cancer specialist at Institut Gustave Roussy. Professor Soria trained as a medical oncologist and obtained the Silver medal from Paris Medical School in 1997. He gained a postgraduate degree and a PhD degree in molecular biology (fundamental basis of oncogenesis) in 2001, and completed his training with a two-year post-doctoral fellowship at MD Anderson Cancer Center, Houston, USA, where he has held an Adjunct Professorship since 2012. Professor Soria is also a member of the thoracic pathology committee at Gustave Roussy Cancer Center. He is a recognized expert on targeted therapies, immunotherapy and lung cancer. His main research interests are: early clinical development, pharmacodynamic biomarkers, lung cancer, immunotherapy and personalized medicine. He is also involved in translational research aspects related to precision medicine and tumor progression notably in lung cancer models (INSERM unit 981). Only shareholders having registered their shares at least two business days prior to the date of the AGM, by midnight Paris time, will be able to attend. Shareholders holding "au porteur" (bearer) shares will need to obtain an "attestation de participation" (certificate of shareholding) from their brokers. This "attestation de participation" must be attached to the proxy form or to the appropriate voting form if shareholders wish to designate a proxy or vote by post. The "attestation de participation" may replace the admission card for shareholders wishing to attend the AGM in person. Written questions from shareholders must be received from the day of the publication of the official convocation to the AGM up until four business days prior to the AGM (by registered letter, addressed to the registered office, or by e-mail to investors@innate-pharma.com). Shareholders may obtain the legal documentation in preparation of the AGM (as described in article R. 225-83 of the French "Code de Commerce") by sending a request: Innate Pharma S.A. is a clinical-stage biotechnology company with a focus on discovering and developing first-in-class therapeutic antibodies that harness the innate immune system to improve cancer treatment and clinical outcomes for patients. Innate Pharma specializes in immuno-oncology, a new therapeutic field that is changing cancer treatment by mobilizing the power of the body's immune system to recognize and kill cancer cells. The Company's aim is to become a fully-integrated biopharmaceutical company in the area of immunotherapy and focused on serious unmet medical needs in cancer. Innate Pharma has pioneered the discovery and development of checkpoint inhibitors to activate the innate immune system. Innate Pharma's innovative approach has resulted in three first-in-class, clinical-stage antibodies targeting natural killer cell receptors that may address a broad range of solid and hematological cancer indications as well as additional preclinical product candidates and technologies. Targeting receptors involved in innate immunity also creates opportunities for the Company to develop therapies for inflammatory diseases. The Company's expertise and understanding of natural killer cell biology have enabled it to enter into major alliances with leaders in the biopharmaceutical industry including AstraZeneca, Bristol-Myers Squibb and Sanofi. Based in Marseille, France, Innate Pharma has more than 170 employees and is listed on Euronext Paris. Learn more about Innate Pharma at www.innate-pharma.com. This press release contains certain forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. For a discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Document de Reference prospectus filed with the AMF, which is available on the AMF website (http://www.amf-france.org) or on Innate Pharma's website. This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country.


Paoletti X.,Gustave Roussy Cancer Center | Paoletti X.,French Institute of Health and Medical Research | Drubay D.,Gustave Roussy Cancer Center | Drubay D.,French Institute of Health and Medical Research | Collette L.,European Organization for Research and Treatment of Cancer Headquarters
Clinical Cancer Research | Year: 2017

The most commonly used method for dose finding, the 3 þ 3, has poor performance. New adaptive designs are more efficient. Nevertheless, they have reached a maximum performance level, and further improvement requires either larger sample sizes or outcomes measures richer than the simplistic severe toxicity measured at cycle 1. ©2017 AACR.


Dupuis J.,Henri Mondor University Hospital | Morschhauser F.,Claude Huriez University Hospital | Ghesquieres H.,Leon Berard Cancer Center | Tilly H.,Henri Becquerel Cancer Center | And 14 more authors.
The Lancet Haematology | Year: 2015

BACKGROUND: Romidepsin is a histone deacetylase inhibitor approved in the USA for patients with recurrent or refractory peripheral T-cell lymphoma and has shown activity in this setting with mainly haematological and gastrointestinal toxicity. Although it has limited efficacy, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used for treatment of de-novo peripheral T-cell lymphoma. We aimed to assess the safety, tolerability, and activity of romidepsin combined with CHOP in patients with previously untreated disease. METHODS: We enrolled patients aged 18-80 years with histologically proven, previously untreated, peripheral T-cell lymphoma (Eastern Cooperative Oncology Group performance status ≤2) into a dose-escalation (phase 1b) and expansion (phase 2) study at nine Lymphoma Study Association centres in France. In the dose-escalation phase, we allocated consecutive blocks of three participants to receive eight 3 week cycles of CHOP (intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2 mg] on day 1 and oral prednisone 40 mg/m2 on days 1-5) in association with varying doses of romidepsin. The starting dose was 10 mg/m2 intravenously on days 1 and 8 of each cycle, and we used a 3 + 3 design. We assessed dose-limiting toxicities only during the first two cycles. The primary endpoint was to determine the recommended dose for the combination. For the phase 2 study, we aimed to increase the cohort of patients receiving the recommended dose to a total of 25 patients. Patients were assessed for safety outcomes at least twice per cycle according to the Common Terminology Criteria for Adverse Events, version 4.0. Safety analyses included all patients who received at least one dose of romidepsin and CHOP. This trial is registered at the European Clinical Trials Database (EudraCT), number 2010-020962-91 and ClinicalTrials.gov, number NCT01280526. FINDINGS: Between Jan 13, 2011, and May 21, 2013, we enrolled 37 patients (18 treated in phase 1b and 19 patients in phase 2). Three of six patients initially treated at 10 mg/m2 had a dose-limiting toxicity. The dose-escalation committee decided to modify the study protocol to redefine dose-limiting toxicities with regard to haematological toxicity. Three patients were treated with 8 mg/m2 of romidepsin, an additional three at 10 mg/m2 (one dose-limiting toxicity), and six patients at 12 mg/m2 (three dose-limiting toxicities). We chose romidepsin 12 mg/m2 as the recommended dose for phase 2. Of the 37 patients treated, three had early cardiac events (two myocardial infarctions and one acute cardiac failure). No deaths were attributable to toxicity. 25 (68%) of 37 patients had at least one serious adverse event. Overall, the most frequent serious adverse events were febrile neutropenia (five [14%] of 37 patients), physical health deterioration (five [14%]), lung infection (four [11%]), and vomiting (three [8%]). 33 (89%) of patients had grade 3-4 neutropenia, and 29 (78%) had grade 3-4 thrombocytopenia. INTERPRETATION: Romidepsin can be combined with CHOP but this combination should now be tested in comparison to CHOP alone in a randomised trial. FUNDING: Celgene. © 2015 Elsevier Ltd. All rights reserved.


Poortmans P.M.,Radboud University Nijmegen | Poortmans P.M.,Institute Verbeeten | Collette S.,European Organization for Research and Treatment of Cancer EORTC | Kirkove C.,Catholic University of Leuven | And 23 more authors.
New England Journal of Medicine | Year: 2015

Background The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown. METHODS We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer. RESULTS Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P = 0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P = 0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P = 0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P = 0.02). Acute side effects of regional nodal irradiation were modest. CONCLUSIONS In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. © 2015 Massachusetts Medical Society.


Lavaud P.,Gustave Roussy Cancer Center | Andre F.,Gustave Roussy Cancer Center | Andre F.,University Paris - Sud
BMC Medicine | Year: 2014

Breast cancers over-express the human epidermal growth factor receptor 2 (HER2) in about 15% of patients. This transmembrane tyrosine kinase receptor activates downstream signaling pathways and leads to proliferation of cancer cells. Trastuzumab, an anti-HER2 monoclonal antibody, improves outcome in women with early and metastatic breast cancer. Resistance to trastuzumab involves the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway, truncation of the Her2 receptor or lack of immune response. The last decade has seen major advances in strategies to overcome resistance to trastuzumab. This includes the development of antibody-drug conjugates, dual HER2 inhibition strategies, inhibition of PI3K/mTOR pathway and development of modulators of immune checkpoints. © 2014 Lavaud and Andre; licensee BioMed Central.


Honore C.,The Surgical Center | Amroun K.,The Surgical Center | Vilcot L.,Gustave Roussy Cancer Center | Mir O.,Gustave Roussy Cancer Center | And 5 more authors.
Annals of Surgical Oncology | Year: 2015

Background: With nearly 450 cases reported since 1991, desmoplastic small round cell tumor (DSRCT) is a rare abdominal tumor typically arising in adolescent and young adult white men. With no large series described, the best therapeutic strategy remains unclear. Methods: All consecutive patients treated in our tertiary care center between January 1991 and December 2013 for a DSRCT were retrospectively studied. Results: Thirty-eight patients with a median age of 27 years (range 13–57 years) were identified; 71 % were men. At the time of diagnosis, 47.4 % patients had extraperitoneal metastases (EPM): 78 % were located in the liver and 11 % were located in the lungs. Fourteen patients (37 %) were treated exclusively with systemic chemotherapy, with a median survival of 21.1 months. Twenty-three patients underwent surgery, 12 (52 %) experienced complete removal of all macroscopic disease, 5 (21.7 %) received additional intraperitoneal chemotherapy, and 7 (30 %) received postoperative whole abdominopelvic radiotherapy (WAP RT). With a median follow-up of 59.9 months, the median survival was 37.7 months, and the median disease-free survival was 15.5 months. The factors predictive of 3-year overall survival were the absence of EPM, complete surgical resection, postoperative WAP RT, and postoperative chemotherapy. The intraperitoneal chemotherapy had no impact on overall survival. Conclusions: DSRCT is a rare and aggressive disease. In patients without EPM, a multimodal treatment combining systemic chemotherapy, complete macroscopic resection, and postoperative WAP RT could enable prolonged survival. No benefit of surgery was demonstrated for patients with EPM. The value of associated hyperthermic intraperitoneal chemotherapy remains unproven. © 2014, Society of Surgical Oncology.


Honore C.,Gustave Roussy Cancer Center | Meeus P.,Center Leon Berard | Stoeckle E.,Institute Bergonie | Bonvalot S.,Institute Curie
Journal de Chirurgie Viscerale | Year: 2015

Four thousand new cases of soft tissue sarcomas are diagnosed each year in France, 23% of which are localized in the abdomen and pelvis; the treatment of non-metastatic tumor is based on wide surgical resection, the quality of which determines the long-term outcome. To ensure appropriate care, the European Society for Medical Oncology (ESMO) recommends that any patient with an unexplained soft tissue mass (of any size for deep lesions or of>5cm for superficial lesions) be referred to a specialized center with capacities for multidisciplinary team decision; appropriate imaging should be performed prior to treatment and a percutaneous image-guided needle biopsy should be routinely performed. In France, clinical and pathology networks (NetSarc and RRePS) currently offer patients a structured means to make a systematic diagnosis of soft tissue sarcoma and help to provide access to appropriate treatment in a specialized center. © 2015 Elsevier Masson SAS.


News Article | December 8, 2016
Site: www.eurekalert.org

The prize, donated by Frédérique Brupbacher in memory of her husband, Charles Rodolphe Brupbacher, will be awarded for the thirteenth time in February 2017. Endowed with prize money of CHF 100,000 for each award, the prize is considered one of the most prestigious research distinctions in the international cancer community. The prize goes to three outstanding researchers, this time for groundbreaking research on the impact of epigenetics, cell death, and gut microbiota on the progression of cancer. This research lays important groundwork for improving the understanding of cancer and for developing new, targeted therapies. Adrian Bird, recipient of the first prize, is Professor of Genetics at the Wellcome Trust Centre for Cell Biology of the University of Edinburgh. His work focuses on the interaction of genetics and epigenetics, an aspect of cancer development that has received little research attention to date. Methyl groups, which are added to the DNA, regulate the activity of numerous genes. The majority of the human genome carries such methyl groups. Within the genom there are also small regions, known as CpG islands, without such epigenetic marks. In tumor cells, CpG islands are often methylated, and these DNA methylation changes generally trigger an abnormal inactivation of the affected gene. Adrian Bird and his team investigated proteins that bind to CpG islands and influence DNA methylation and other epigenetic characteristics. These proteins, which control the interaction of genome and epigenome, are often deregulated in cancer and may thus play a significant role in oncogenesis. The second prize is being conferred jointly on physician Giudo Kroemer from the Centre de Recherche des Cordeliers of the Université Paris Descartes and immunologist Laurence Zitvogel from the Laboratory for Tumor Immunology and Immunotherapy of the Gustave Roussy Cancer Center. Their research focuses on how the immune system influences the development and treatment of cancer. The work of Guido Kroemer focuses on apoptosis - programmed cell death - the process by which cells self-eliminate when they become impaired. A further process, autophagy, plays a significant role in how cells survive the effects of toxic substances, such as during chemotherapy. Kroemer and his team were able to demonstrate that the death of cancer cells can stimulate the immune system, if autophagy has been activated in advance. This reactivates immunogenicity of the tumor cells, thus making them "visible" to defense cells and allowing them to be efficiently eliminated. The type of immune reaction triggered by dying cancer cells is thus decisive for the success of cancer treatment. In various papers, Laurence Zitvogel and her research team demonstrated that gut microbiota not only influences its immediate surroundings, but also affects the immune response to cancer cells in other regions of the body. They further proved that the bacteria strains Escherichia hirae and Barnesiella intestinihominis substantially improve the success of chemotherapy with cyclophosphamide in patients with lung and ovarian cancer. Bacteria from the Bacteroidales, Burkholderiales, and Bifidobacteriales groups also affect tumor micro-environment and enhance the effectiveness of antibody therapies for skin cancer. Until now, it was unknown - and unexpected - that gut microbiota can enhance the body's immune reaction to cancer cells outside of the gut.

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