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Insulin Resistance Ir And Prognosis Of Metastatic Breast Cancer Mbc Patients

Metastatic Breast Cancer: Endocrine Therapy Landscape Reshaped Salkeni Ma, Hall Sj - Avicenna J Med

Metastatic Breast Cancer: Endocrine Therapy Landscape Reshaped Salkeni Ma, Hall Sj - Avicenna J Med

Breast cancer is considered, in many cases, a chronically relapsing form of cancer. This is even more evident in the hormone receptor (HR)-positive operable disease as some patients remain at the risk of relapse even beyond 20 years from diagnosis. Although the annual risk of relapse is highest in the first 5 years from the diagnosis, it can persist well beyond 5 years. A post hoc analysis of the annual hazard rate of recurrence for 4104 patients who participated in the International Breast Cancer Study Group trials between 1978 and 1985 found that patients with a node-negative disease have a recurrence risk of 2.0%, 2.1%, and 1.1% annually for years 1015, 1520, and 2025 from diagnosis, respectively. For patients with node-positive disease (N1, 13 involved nodes), the recurrence risk was found to be at 3.0%, 3.5%, and 1.5%, for the same time intervals, respectively. [1] Approximately 5%10% of patients with Stage I breast cancer, 15%20% of patients with Stage II, and ~50% of patients with stage III will recur distally and are likely to die from their disease. [2] , [3] On top of that, about 5%10% of newly diagnosed patients with metastatic breast cancer (MBC) have de novo disease. [4] , [5] Historically, median survival of patients with MBC that is hormone-receptor positive, human epidermal growth factor receptor 2 (HER2)-negative who were diagnosed and treated decades ago has been reported to range between 16 and 26 months. [6] , [7] In comparison, the introduction of cyclin-dependent kinase (CDK) inhibitors and mechanistic target of rapamycin (mTOR) inhibitors, combinations with available endocrine therapies recently led to significantly improved progression-free survival (PFS) and overall survival (OS) that surpassed previously reported outcomes. [6] , [8] , [9] , [1 Continue reading >>

Her2 Therapy: Molecular Mechanisms Of Trastuzumab Resistance

Her2 Therapy: Molecular Mechanisms Of Trastuzumab Resistance

HER2 therapy: Molecular mechanisms of trastuzumab resistance 1Department of Breast Medical Oncology, Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Holcombe Blvd, Houston, Texas 77030-4009, USA 1Department of Breast Medical Oncology, Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Holcombe Blvd, Houston, Texas 77030-4009, USA 2Department of Molecular and Cellular Oncology, Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Holcombe Blvd, Houston, Texas 77030-4009, USA 3The University of Texas Graduate School of Biomedical Sciences at Houston, 6767 Bertner Ave, Houston, Texas 77030, USA 1Department of Breast Medical Oncology, Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Holcombe Blvd, Houston, Texas 77030-4009, USA 2Department of Molecular and Cellular Oncology, Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Holcombe Blvd, Houston, Texas 77030-4009, USA 3The University of Texas Graduate School of Biomedical Sciences at Houston, 6767 Bertner Ave, Houston, Texas 77030, USA This article has been cited by other articles in PMC. Trastuzumab is a monoclonal antibody targeted against the HER2 tyrosine kinase receptor. The majority of patients with metastatic breast cancer who initially respond to trastuzumab develop resistance within one year of treatment initiation, and in the adjuvant setting 15% of patients still relapse despite trastuzumab-based therapy. In this review, we discuss potential mechanisms of antitumor activity by trastuzumab, and how these mechanisms become altered to promote therapeutic resistance. We Continue reading >>

Programme - European School Of Oncology

Programme - European School Of Oncology

Worldwide survey and call to action (Chairs: F. Cardoso, PT and D. CJ M. Corneliussen-James, US) Welcome and introduction (D. CJ M. Corneliussen-James, US) The mBCVision 2025 Project: why, how and what? (S. Chaudhuri, US) Main findings of the mBCVision 2025 Project (F. Cardoso, PT) Main findings of the mBCVision 2025 Project: implications for patients (D. CJ M. Corneliussen-James, US) Discussion on call to action points (F. Cardoso, PT and D. CJ M. Corneliussen-James, US) I am Anna Video presentation and viewing (S. Ginsberg, CA and A. Craig, CA) Specific issues of young women with advanced breast cancer (Chairs: E. Papadopoulos, CY and D. Spence, AU) Presentation of key issues (L. Travado, PT) - Relationships/sexuality/personality/social image - how women relate to themselves, their partners and their social networks - Practical issues- work, finances, home support, including childcare - Emotional concerns of those close to you, including children, partners, parents What are the requirements to assist women to address these issues? (D. Spence, AU) Empowering women (E. Papadopoulos, CY) Opening session (Chairs: F. Cardoso, PT and L. Norton, US) Welcome to Lisbon (Maria Cavaco Silva, First Lady of the Portuguese Republic) Opening and introduction (F. Cardoso, PT) Keynote lecture: METAvivor: fighting prejudice! (D. CJ M. Corneliussen-James, US) Optimal management of HER-2+ ABC (Chairs: Shinji Ohno, JP and E.P. Winer, US) Is there an optimal treatment sequence? (S.M. Swain, US) Resistance to anti-HER-2 agents: what's new (I.E. Krop, US) Long term survivors specific issues (K. Gelmon, CA) Long term survivors: living on borrowed time (S.A. Mertz, US) Best abstract presentations (Chairs: A. Costa, IT/CH and K.A. Sabelko, US) Unmet psychosocial and quality of life needs of pa Continue reading >>

Most Cited Clinical Breast Cancer Articles

Most Cited Clinical Breast Cancer Articles

Most Cited Clinical Breast Cancer Articles The most cited articles published since 2013, extracted from Scopus . Volume 13, Issue 4, January 2013, Pages 299-306 Shelli Kesler | S. M. Hadi Hosseini | Charles Heckler | Michelle Janelsins | Oxana Palesh | Karen Mustian | Gary Morrow Difficulties with thinking and problem solving are very common among breast cancer survivors. We tested a computerized cognitive training program for 41 breast cancer survivors. The training program was associated with significant improvements in thinking and problem-solving skills. Our findings demonstrate potential for our online, home-based cognitive training program to improve cognitive difficulties among breast cancer survivors. Background: A majority of breast cancer (BC) survivors, particularly those treated with chemotherapy, experience long-term cognitive deficits that significantly reduce quality of life. Among the cognitive domains most commonly affected include executive functions (EF), such as working memory, cognitive flexibility, multitasking, planning, and attention. Previous studies in other populations have shown that cognitive training, a behavioral method for treating cognitive deficits, can result in significant improvements in a number of cognitive skills, including EF. Materials and Methods: In this study, we conducted a randomized controlled trial to investigate the feasibility and preliminary effectiveness of a novel, online EF training program in long-term BC survivors. A total of 41 BC survivors (21 active, 20 wait list) completed the 48 session training program over 12 weeks. The participants were, on average, 6 years after therapy. Results: Cognitive training led to significant improvements in cognitive flexibility, verbal fluency and processing speed, with margina Continue reading >>

Deciphering The Role Of Insulin-like Growth Factor-i Receptor In Trastuzumab Resistance

Deciphering The Role Of Insulin-like Growth Factor-i Receptor In Trastuzumab Resistance

Deciphering the Role of Insulin-Like Growth Factor-I Receptor in Trastuzumab Resistance Departments of Pharmacology, Hematology and Medical Oncology, School of Medicine; Winship Cancer Institute; Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Suite 5001, 1510 Clifton Road, Atlanta, GA 30322, USA Received 25 April 2012; Accepted 19 June 2012 Copyright 2012 Rita Nahta. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Resistance to the HER2-targeted antibody trastuzumab is a major clinical concern in the treatment of HER2-overexpressing metastatic breast cancer. Increased expression or signaling of the insulin-like growth factor-I receptor (IGF-IR) has been reported in a subset of cell lines and clinical samples derived from trastuzumab-resistant breast cancers. Genetic and pharmacologic inhibition of IGF-IR signaling has been shown to improve response to trastuzumab in trastuzumab-nave and trastuzumab-resistant models. In this paper, we will discuss the role of IGF-IR signaling in trastuzumab resistance. Further, we will discuss cotargeting IGF-IR and HER2 as a potential therapeutic strategy for HER2-over-expressing breast cancers that have progressed on trastuzumab treatment. Trastuzumab (Herceptin; Genentech, San Francisco, CA) is a humanized monoclonal antibody against an epitope in the extracellular domain of the HER2 receptor tyrosine kinase protein [ 1 ]. HER2 is overexpressed, generally due to amplification of the her2 gene, in approximately 2030% of human metastatic breast cancers (MBC), and is associated with reduced disease-fr Continue reading >>

Disease Markers - Volume 26, Issue 4

Disease Markers - Volume 26, Issue 4

Authors: Govindan, Sujatha | Shaik, Noor Ahmad | Vedicherla, Bhavani | Kodati, Vijayalakshmi | Rao, Kaipa Prabhakar | Hasan, Qurratulain Abstract: Endometriosis and fibroids are estrogen-dependent benign pathologies of the uterus, which account for infertility and pelvic pain along with dysmenorrhea in women. Suppression of the disease and recurrence after discontinuing hormone therapy strongly suggests that these are responsive to hormones, especially estrogen, which acts via its receptor. A T/C SNP in intron 1 and exon 2 boundary of estrogen receptor (ER) gene recognized by PvuII enzyme has been associated with several female pathologies like breast cancer, osteoporosis, endometriosis and fibroids in various ethnic groups. The aim of the present study was to assess this ER T/C polymorphism in endometriosis and fibroid patients from Asian Indian population. Genomic DNA was isolated from 367 women, who included 110 cases of endometriosis, 142 cases of uterine fibroids and 115 healthy age matched women volunteers. PCR was carried out to amplify ER gene followed by restriction digestion with Pvu II. Results indicate a significant association of C allele with both endometriosis [OR=2.6667, 95% CI=1.4166 to 5.0199; p < 0.05] and fibroids [2.0833, 95% CI=1.1327 to 3.8319; p < 0.05]. Further studies are needed in larger population to establish ER C allele as a risk marker for endometriosis and fibroids in Asian Indian women. Ethnicity, race, diet etc may play a role in susceptibility to endometriosis and fibroids and further studies are warranted in this area. Show more Keywords: Estrogen receptor, Pvu II polymorphism, Intron 1, endometriosis, fibroids Authors: Fintelman-Rodrigues, N. | Corra, J.C. | Santos, J.M. | Pimentel, M.M.G. | Santos-Rebouas, C.B. Abstract: Recent evi Continue reading >>

Resistance Of Her2-targeted Therapy In Breast Cancer

Resistance Of Her2-targeted Therapy In Breast Cancer

Trastuzumab is a monoclonal antibody targeted against the human epidermal growth factor receptor (HER) 2 tyrosine kinase receptor, which is overexpressed in approximately 25% of invasive breast cancers. The majority of patients with metastatic breast cancer who initially respond to trastuzumab, however, demonstrate disease progression within 1 year of treatment initiation. Preclinical studies have indicated several molecular mechanisms that could contribute to the development of trastuzumab resistance. Increased signaling via the phosphatidylinositol 3-kinase/Akt pathway could contribute to trastuzumab resistance because of activation of multiple receptor pathways that include HER2-related receptors or non-HER receptors such as the insulin-like growth factor 1 receptor, which appears to be involved in a cross-talk with HER2 in resistant cells. Additionally, loss of function of the tumor suppressor PTEN gene, the negative regulator of Akt, results in heightened Akt signaling that leads to decreased sensitivity to trastuzumab. Decreased interaction between trastuzumab and its target receptor HER2, which is due to steric hindrance of HER2 by cell surface proteins such as mucin-4 (MUC4), may block the inhibitory actions of trastuzumab. Novel therapies targeted against these aberrant molecular pathways offer hope that the effectiveness and duration of response to trastuzumab can be greatly improved. Trastuzumab (Herceptin, Genentech Inc., San Francisco, CA) is a recombinant humanized monoclonal antibody directed against the extracellular domain of the human epidermal growth factor receptor 2 (HER2 or ErbB-2) protein.[ 1 ] Currently, trastuzumab is the only HER2-targeted therapy approved by the FDA for the treatment of metastatic breast cancer (MBC). The HER2 protein is an i Continue reading >>

Breast Cancer Conferences 2016 Usa | Conferenceseries Llc

Breast Cancer Conferences 2016 Usa | Conferenceseries Llc

University of Florida College of Medicine, USA Shahla Masood, M.D. is an professor in the department of Pathology and Laboratory Medicine at the University of Florida College of MedicineJacksonville. She is Chair, Department of Pathology and Laboratory Medicine; Program Director, Breast Pathology Fellowship; Medical Director, Breast Health Center; Program Director, Cytopathology Fellowship; Director of Research. Clinical Special Interests: Breast pathology , cytopathology. Research Special Interests: Early breast cancer detection; use of minimally invasive procedures to provide optimal samples for analysis; prognostic/predictive index. During the last several years, increased public awareness, advances in breast imaging and enhanced screening programs have led to early breast cancer detection and attention to cancer prevention . The numbers of image-detected biopsies have increased and pathologists are expected to provide more information with smaller tissue samples. These biopsies have resulted in detection of increasing numbers of high-risk proliferative breast disease and in situ cancers. The general hypothesis is that some forms of breast cancers may arise from established forms of ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH) and possibly from more common forms of ductal hyperplasia. However, this is an oversimplification of a very complex process, given the fact that the majority of breast cancers appears to arise de-novo or from a yet unknown precursor lesion. Currently, ADH and DCIS are considered as morphologic risk factors and precursor lesions for breast cancer. However, morphologic distinction between these two entities has remained a real issue that continues to lead to over-diagnosis and overtreatment. Aside from morphologic simila Continue reading >>

Abc3 Final Book By Cancer World Magazine - Issuu

Abc3 Final Book By Cancer World Magazine - Issuu

Advanced Breast Cancer Third International Consensus Conference Poster sessionBP: Best poster presentation; PO: Poster presentationBP38 Metastatic breast cancer in Canada: waiting for treatment. Niya Chari, CA Is there a different treatment response between visceral and non-visceral metastaticbreast cancer: a systematic literature review of registration trials. Rachel Wrstlein, DE BP103 Electrochemotherapy in the treatment of cutaneous metastases from breast cancer:a multicenter cohort analysis. Roberto Agresti, ITBP129 Insulin resistance (IR) and prognosis of metastatic breast cancer (MBC) patients.Nicoletta Provinciali, IT Effective advocacy for women with metastatic breast cancer: a European perspective.Susan Knox, IT Unmet needs of Australian women with metastatic breast cancer with financiallydependent children: the consumer perspective. Danielle Spence, AU Middle Eastern ABC/MBC patients: overcoming the triple-burden of stigmatization, lackof information and recurrent illness. Rania Azmi, KW Make your dialogue count survey: addressing communication gaps between patientswith advanced breast cancer, their caregivers and oncologists and understandinginformation and emotional needs to improve treatment and side effect management.Helen L. Coons, US Fight, live, keep smiling: the first Italian blog about metastatic breast cancer (MBC)addressed to the general public. A quali-quantitative analysis of all the comments postedonline on the blog of the Europa Donna Italia MBC Working Group. Francesca Balena, IT In Our Shoes: raising the voices of MBC patients. Lori Marx-Rubiner, US Information needs of young women with metastatic breast cancer to manage theirtreatment, side effects and clinical trials. Medha Sutliff, US I AM ANNA: Exploring metastatic breast cancer through t Continue reading >>

Breast Cancer And Metastasis: On The Way Toward Individualized Therapy

Breast Cancer And Metastasis: On The Way Toward Individualized Therapy

Breast Cancer and Metastasis: On the Way Toward Individualized Therapy 1 Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A. 2 Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A. Correspondence to: Ana Maria Gonzalez-Angulo, Associate Professor. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 1354, 1515 Holcombe Boulevard, Houston, TX 77030-4009, U.S.A. E-mail: agonzalez{at}mdanderson.org Breast cancer (BC) remains the most common cancer type diagnosed in women. Although targeted therapies have improved patient survival for advanced BC, these tumors frequently relapse due to drug resistance mechanisms. A systems biology approach integrates DNA, RNA and protein alterations generated from multidimensional platforms to better understand the mechanisms that regulate the metastatic process. Downstream functional analyses in pre-clinical studies might integrate the role of these aberrations into the cell, leading to discovery of new therapeutic targets. In the present report, we review relevant findings associated with genomic, transcriptomic and proteomic analyses and the contribution of the systems biology concept to the interpretation of these data in the metastatic context. Also, we highlight the importance of re-designing clinical trials towards metastasis prevention for improvement of personalized care. In 2012, invasive BC is expected to account for 29% (226,870) of all newly-diagnosed cancer cases and for 14% (39,510) of all cancer deaths in women in USA ( 1 ). Although targeted therapies have improved patient survival for advanced BC, these tumors frequently relapse due to drug resistance mechanisms. Some evidence have sh Continue reading >>

Pretreatment Insulin Levels As A Prognostic Factor For Breast Cancer Progression

Pretreatment Insulin Levels As A Prognostic Factor For Breast Cancer Progression

Pretreatment Insulin Levels as a Prognostic Factor for Breast Cancer Progression aSan Raffaele Roma Open University, Rome, Italy bInterinstitutional Multidisciplinary Biobank, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy cDepartment of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, Tor Vergata University of Rome, Rome, Italy dAnatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy eDepartment of Pathology, San Giovanni Hospital-Addolorata, Rome, Italy fDepartment of Surgery, San Giovanni Hospital-Addolorata, Rome, Italy Correspondence: Patrizia Ferroni, M.D., Ph.D., San Raffaele Roma Open University, IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00166, Rome, Italy. Telephone: 39 06 52253733; E-Mail: patrizia.ferroni{at}sanraffaele.it Published online before print July 7, 2016. Disclosures of potential conflicts of interest may be found at the end of this article. Based on the hypothesis that impaired glucose metabolism might be associated with survival outcomes independently of overt diabetes, we sought to investigate the prognostic value of routinely used glycemic parameters in a prospective study of breast cancer (BC) patients. Fasting blood glucose, insulin and HbA1c levels, and insulin resistance (assessed by the Homeostasis Model Assessment [HOMA] index) at diagnosis were evaluated in 286 nondiabetic BC patients (249 with primary cancer, 37 with metastatic) with respect to those parameters possible associations with clinicopathological features and survival outcomes. As a control group, 143 healthy women matched in a 2:1 ratio for age, blood lipid levels, and body mass index were also investigated. Fasting blood glucose level (mean SD: 99 26 vs. 85 15 m Continue reading >>

Po71 Monitoring Therapy Response In Metastatic Breast Cancer Using Tumour Markers Ca15-3 And Tps (english)

Po71 Monitoring Therapy Response In Metastatic Breast Cancer Using Tumour Markers Ca15-3 And Tps (english)

Socio-demographic, clinical, and health-related factors associated with breast reconstruction A nationwide cohort study Bodilsen, Anne / Christensen, Sren / Christiansen, Peer / Damsgaard, Tine E. / Zachariae, Robert / Jensen, Anders B. | 2015 Breast cancer metastasis burden in sentinel nodes analysed using one-step nucleic acid amplification predicts axillary nodal status Milner, Thomas D. / de Lusignan, Simon / Jones, Simon / Jackson, Peter A. / Layer, Graham T. / Kissin, Mark W. / Irvine, Tracey E. | 2015 Mammographic breast density: Predictive value for pathological response to neoadjuvant chemotherapy in breast cancer patients Elsamany, S. / Alzahrani, A. / Abozeed, W.N. / Rasmy, A. / Farooq, M.U. / Elbiomy, M.A. / Rawah, E. / Alsaleh, K. / Abdel-Aziz, N.M. | 2015 Neurological complications of breast cancer: A prospective cohort study Pereira, Susana / Fontes, Filipa / Sonin, Teresa / Dias, Teresa / Fragoso, Maria / Castro-Lopes, Jos Manuel / Lunet, Nuno | 2015 Survival time according to the year of recurrence and subtype in recurrent breast cancer Nakano, Masahiro / Fujisue, Mamiko / Tashima, Rumiko / Okumura, Yasuhiro / Nishiyama, Yasuyuki / Ohsako, Tomofumi / Toyozumi, Yasuo / Arima, Nobuyuki / Nishimura, Reiki | 2015 Preeclampsia and breast cancer: The influence of birth characteristics Pacheco, Nadja Livia Pekkola / Andersen, Anne-Marie Nybo / Kamper-Jrgensen, Mads | 2015 Surgical margin reporting in breast conserving surgery: Does compliance with guidelines affect re-excision and mastectomy rates? Persing, Sarah / Jerome, Mairin A. / James, Ted A. / Callas, Peter / Mace, John / Sowden, Michelle / Goodwin, Andrew / Weaver, Donald L. / Sprague, Brian L. | 2015 Challenges in optimizing care in advanced breast cancer patients: Results of an international survey Continue reading >>

"irs1 - Insulin Receptor Substrate 1 - Homo Sapiens (human) - Irs1 Gene & Protein"

Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that in humans is encoded by the IRS-1 gene.[5] It is a 131 kDa protein with amino acid sequence of 1242 residues.[6] It contains a single pleckstrin homology (PH) domain at the N-terminus and a PTB domain ca. 40 residues downstream of this, followed by a poorly conserved C-terminus tail.[7] Together with IRS2, IRS3 (pseudogene) and IRS4, it is homologous to the Drosophila protein chico, whose disruption extends the median lifespan of flies up to 48%.[8] Similarly, Irs1 mutant mice experience moderate life extension and delayed age-related pathologies.[9] Function[edit] Insulin receptor substrate 1 plays a key role in transmitting signals from the insulin and insulin-like growth factor-1 (IGF-1) receptors to intracellular pathways PI3K / Akt and Erk MAP kinase pathways. Tyrosine phosphorylation of IRS-1 by insulin receptor (IR) introduces multiple binding sites for proteins bearing SH2 homology domain, such as PI3K, Grb-2/Sos complex and SHP2. PI3K, involved in interaction with IRS-1, produces PIP3, which, in turn, recruits Akt kinase. Further, Akt kinase is activated via phosphorylation of its T308 residue and analogous sites in PKC by PDK1. This phosphorylation is absent in tissues lacking IRS-1. The cascade is followed by glucose uptake. Grb-2/Sos complex, also known as RAS, signaling results in ERK1/2 activation. IRS-1 signal transduction may be inhibited by SHP2 in some tissues.[7] Tyrosine phosphorylation of the insulin receptors or IGF-1 receptors, upon extracellular ligand binding, induces the cytoplasmic binding of IRS-1 to these receptors, through its PTB domains. Multiple tyrosine residues of IRS-1 itself are then phosphorylated by these receptors. This enables IRS-1 to activate several signa Continue reading >>

Boehringer Ingelheim, Eli Lilly Collaborate In Clinical Trial For Metastatic Breast Cancer Combo Therapy

Boehringer Ingelheim, Eli Lilly Collaborate In Clinical Trial For Metastatic Breast Cancer Combo Therapy

Boehringer Ingelheim and Eli Lilly will collaborateon a Phase 1b clinical trial toassess the safety and tolerability of Boehringer Ingelheims BI 836845 in combination with Lillys abemaciclib (LY2835219) to treat patients with HR+/HER2- metastatic breast cancer (mBC). The companies believe these two agents used in combination could offer more complete pathway interference and potentially extend cell cycle arrest. For patients with HR+/HER2- mBC, this could reverse resistance to hormone therapy . The new collaboration, which is based on Phase 1b data, has the potential to expand to Phase 2 clinical trials in patients with HR+/HER2- mBC as well as other solid tumors. Patient enrollment is planned to commence later this year. Boehringer Ingelheim will act as sponsor of the trial program. Richard Gaynor, MD, senior vice president of product development and medical affairs for Lilly Oncology, said in a press release the company was pleased to partner withBoehringer Ingelheim for the combination project, and that Lilly has an active Phase 3 trialunderway for abemaciclib. For patients living with metastatic breast cancer, the limited treatment options available make this an important area of focus for our efforts to advance the most innovative treatments, he said. Dr. Mehdi Shahidi, medical head of Solid Tumor Oncology at Boehringer Ingelheim, said Boehringer is excited about the collaboration to investigate a novel combination of two compounds that have individually shown promising results in metastatic breast cancer and have a complementary mode of action. We hope that this study will lay foundations for making much-needed new therapies available to patients with metastatic breast cancer, he said. BI 836845 is a humanized IgG1 insulin-like growth factor (IGF) monoclonal anti Continue reading >>

Clinmed International Library | Overcoming Endocrine Resistance In Hormone-receptor Positive Advanced Breast Cancer-the Emerging Role Of Cdk4/6 Inhibitors | International Journal Of Cancer And Clinical Research |

Clinmed International Library | Overcoming Endocrine Resistance In Hormone-receptor Positive Advanced Breast Cancer-the Emerging Role Of Cdk4/6 Inhibitors | International Journal Of Cancer And Clinical Research |

International Journal of Cancer and Clinical Research Overcoming Endocrine Resistance in Hormone-Receptor Positive Advanced Breast Cancer-The Emerging Role of CDK4/6 Inhibitors Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, USA *Corresponding author: Ciara C O'Sullivan, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, 20892, Bethesda MD, USA, E-mail: ciara.o'[email protected] Int J Cancer Clin Res, IJCCR-2-029, (Volume 2, Issue 4), Review Article; ISSN: 2378-3419 Received: July 28, 2015 | Accepted: October 10, 2015 | Published: October 14, 2015 Citation: O'Sullivan CC (2015) Overcoming Endocrine Resistance in Hormone-Receptor Positive Advanced Breast Cancer-The Emerging Role of CDK4/6 Inhibitors. Int J Cancer Clin Res 2:029. 10.23937/2378-3419/2/4/1029 Copyright: 2015 O'Sullivan CC. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Dysregulation of the cyclin D and cyclin-dependent kinase (CDK) pathway in cancer cells may inhibit senescence and promote cellular proliferation. By using various different mechanisms, malignant cells may increase cyclin D-dependent activity. The cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway controls the cell cycle restriction point, and is commonly dysregulated in breast cancer; making it a rational target for anticancer therapy. To date, three oral highly selective cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are in various stages of clinical development: PD0332991 (palbociclib), LEE011 (ribociclib) and LY2835219 (abemaciclib). Results from phase I, II and I Continue reading >>

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