Day 16 :
- Organ Defined Cancers | Cancer Genetics | Cancer Biomarkers | Cancer Therapy & Treaments | Cancer Nursing
Chair
Nyla A Heerema
The Ohio State University Wexner Medical Center, USA
Co-Chair
Audrey Claing
Montreal University, Canada
Session Introduction
Nyla A Heerema
The Ohio State University Wexner Medical Center, USA
Title: CpG simulated karyotypic analysis of chronic lymphocytic leukemia (CLL) is a significant prognostic factor and should be performed on all patients
Biography:
Nyla A Heerema is a professor in the Department of Pathology at The Ohio State University Wexner Medical Center. She is the Director of the Cancer Cytogenetics Laboratory there, as well as conducts an active research program. Her areas of research are the cytogenetics of chronic lymphocytic leukemia (CLL) and of pediatric acute lymphoblastic leukemia. She is a member of the CLL Research Consortium, and is the Chairperson of the Cytogenetics Discipline for the Children’s Oncology Group. She has published over 300 articles.
Abstract:
CLL has a variable clinical course and prognostic factors are vital. Metaphase cytogenetics have been minimally informative as CLL cells do not respond to traditional mitogens. CpG stimulates CLL cells to divide in <80% cases. Investigation of karyotypic abnormalities within one year of diagnosis in untreated CLL patients using CpG-stimulation identified complex karyotype (CK) (>3 unrelated abnormalities) that predicted a shorter time to first treatment (TFT) compared to non-CK (NCK, 12 months estimates 45% and 15%, respectively, p=0.0005). Despite a strong correlation of del(17p) with CK, CK predicted TFT independent of del(17p), a known poor prognosticator. Additionally, in patients with either balanced or unbalanced translocation, the good prognosis of mutated IGHV was negated (mutated IGHV translocation present vs absent, HR 3.59, p<0.001; unmutated IGHV translocation present vs absent, HR 1.03, p=0.92, interaction p=0.002). Independent of IGHV and translocation, CK (HR 1.70, p=0.037) remained statistically significant. Patients with Richter’s transformation (RT), an aggressive lymphoma in some CLL patients, exhibited higher risk for death with CK (HR 2.72, p=0.025) than in patients with NCK after R-EPOCH treatment. CK was independently associated with ibrutinib discontinuation due to progression. Although a low percentage of patients treated with ibrutinib experience RT, 6/9 patients with near-tetraploidy detected prior to ibrutinib treatment developed RT. In a multivariable model, both near-tetraploidy (HR 8.66, p<0.0001) and CK (HR 4.78, p=0.01) were independent risk factors for discontinuing ibrutinib due to transformation. In conclusion, CpG-stimulated karyotypes should be performed in CLL patients to identify karyotypic abnormalities that are significant for prognostication.
Charles L Hitchcock
The Ohio State University, USA
Title: Evolution of a system for surgical treatment of adenocarcinomas
Biography:
Charles L Hitchcock is an Emeritus Faculty member of the Department of Pathology at The Ohio State University in Columbus, Ohio USA. For the last 35 years, he has been a member of a multidisciplinary team of physicians, engineers, chemists, and biomedical scientists whose goal is to provide physicians with the resources to optimize the treatment of patients with solid tumors. Their efforts have resulted in over 500 publications and abstracts, multiple research grants, patents, and several biotech companies.
Abstract:
Alice Dragomir
McGill University, Canada
Title: Creating the best clinical and economic evidence to assist decision-making in urological cancers
Biography:
Alice Dragomir is an Assistant Professor at the McGill University, Faculty of Medicine, and Scientist in Health Economics and Outcomes Research at the Research Institute of the McGill University Health Center. She is an Economist and Biostatistician with Master’s degree in Statistics and Doctoral degree in Pharmacoepidemiology and Pharmacoeconomics, from University of Montreal, Canada. She has 14 years of experience in academic research. She was involved in research projects focused on evaluation of health outcomes and health economics related to different treatment strategies, adherence to treatments, health services utilization and disease modeling. Her current research is focused on clinical and economic evaluation of different treatments strategies offered to patients with prostate cancer or other urologic cancers. She has an extended experience in analyzing administrative healthcare databases and disease modeling. Her research represents a valuable tool for decision-makers and clinician leaders while evaluating the clinical and economic impacts of innovative treatments.
Abstract:
M Helena Vasconcelos
University of Porto, Portugal
Title: Unraveling the full role of P-glycoprotein in multidrug resistant cancers
Time : 15:25-15:50
Biography:
M Helena Vasconcelos is an Assistant Professor at FFUP (Faculty of Pharmacy, University of Porto) and Group Leader of the Cancer Drug Resistance Group at i3S/ IPATIMUP. She has done her First degree in Pharmaceutical Sciences (1991) from FFUP in Portugal, MSc (1992) and PhD (1996) from the University of Aberdeen in Scotland. Her current research focuses on the identification and validation of biomarkers and therapeutic targets to overcome drug resistance in cancer and on the activity of small molecules to counteract drug resistance. She has published more than 85 papers published in international journals and with an h-index of 23.
Abstract:
Multidrug resistance (MDR) is often responsible for treatment failure in cancer patients. One of the main reasons for the MDR phenotype of cancer cells is an overexpression of drug-efflux pumps such as P-glycoprotein (P-gp). Recently, my research group, together with international collaborators, compared MDR cells with their drug-sensitive counterparts and verified that MDR cells present metabolic alterations which may be further explored as molecular targets to counteract the MDR phenotype. In addition, my group observed that P-gp may be horizontally transferred by extracellular vesicles (EVs), between MDR and drug-sensitive cells, confirming results from other researchers and indicating that this protein has a stronger influence in the MDR phenotype of tumor cells than had been initially realized. Interestingly, we and collaborators had recently found that the EVs released by MDR cells are enriched in microvesicle-like EVs. However, the work indicates that drug-resistant cells without overexpression of P-gp do not present this enrichment. Thus, we are currently verifying if P-gp could be involved in the release of microvesicles by MDR cells.
Audrey Claing
Montreal University, Canada
Title: ARF proteins as new molecular targets for the treatment of invasive breast cancer
Biography:
Audrey Claing has completed her PhD from the University of Sherbrooke (Canada) in 1997. She has worked at the Laboratory of Dr. Robert J Lefkowitz, 2012 Nobel Laureate, for her Post-doctoral studies at Duke University (USA). She is now the Professor of Pharmacology and Physiology at the Montreal University (Canada). She has published more than 60 papers in reputed journals and has greatly advanced research in the field of G Protein Signaling.
Abstract:
Triple-negative breast cancers (TNBC) are a highly invasive type of breast cancer and associated with poor prognostics. Although, these tumors do not express the typical hormone receptors (ER-, PR-), nor the HER2 receptor, their proliferation and invasive capacities can be enhanced by growth factors such as the epidermal growth factor (EGF). Drugs inhibiting EGF receptor activity have however shown limited effects mainly due to the development of resistance. There is therefore an urgent need to identify new therapeutic targets for the design of therapies that would complement current approaches (surgery, chemo and radiotherapy). We and others have shown that the Ras-related ADP-ribosylation factors (ARF) are another class of small GTPases regulating key features of cancer cells. ARF1 and ARF6, two isoforms best characterized, are highly expressed in cells and tumor tissue of the most aggressive and advanced subtypes of breast cancers. Knock down of ARF1 expression, for example, impairs the ability of breast cancer cells to proliferate, migrate and degrade the extracellular matrix. Furthermore, growth of primary tumors as well as lung metastasis is reduced in a murine xenograft model when expression of the GTPase is inhibited. Our findings have demonstrated that increased levels of ARF1, in non-invasive cells lead to the epithelial-mesenchymal transition (EMT). Overall, our work has identified ARF1 as a molecular switch of cancer progression and thus suggests that limiting the expression/activation of this GTPase could help improve outcome for breast cancer patients.
Hirendra Banerjee
University of North Carolina, USA
Title: An investigation in the role of noncoding RNA’s in epithelial mesenchymal transition (EMT) in prostate cancer
Biography:
Hirendra Nath Banerjee completed his undergraduate degree in Biology & Chemistry and Bachelor of Medicine and Surgery degree from Calcutta University, India. His M.S. in Molecular Biology is from LIU at NY, USA and Ph.D. from Howard University Cancer Center in Washington, D.C. Dr. Banerjee did his post-doctoral training at Yale University and Medical University of South Carolina, USA. As a tenured Professor at Elizabeth City State University under the University of North Carolina system, Dr. Banerjee is involved in cancer research for more than two decades training many talented under graduate and graduate students in the process.
Abstract:
Katarina Jeremić
Clinical Center of Serbia, Serbia
Title: Challenges of therapeutic options in treatment of early stages of endometrial cancer
Biography:
Katarina Jeremić attended Medical School, University of Belgrade in 1996, MD in 2000, PhD in 2006 and Academic Special Studies in Gynecology and Obstetrics.She has 19 years of Clinical Experience, working as Gynecologist at Clinic for Gynecology & Obstetrics Clinical Centre of Serbia, which is the biggest one in whole region. She is currently the Head of Gynecologic Oncology Department and also member of many scientific projects on Cancer and Pregnancy. She worked at the Medical Faculty, University Belgrade as Lecturer and Associate Professor of Gynecology and Obstetrics. She has 50 publications in CC/SCI expanded and JCRindexed, and participated in more than 50 international congresses, with a total number of 150 publications. She is a member of FIGO, ESGO, and other societies.
Abstract:
Conservative approaches of early-stage endometrial carcinoma includes hormonal therapy, in selected group of young patients with endometrial carcinoma with age less than 45 years and wishes to preserve fertility, that shows low grade 1 endometrioid adenocarcinomas limited to the endometrium with MRI excluded myomaterial invasion, without evidence of limphovascular space involvement or extrauterine disease (cervical, ovarian, lymphnodal or any other extra-uterine disease). The diagnosis is proven by two experienced gynoncology pathologists review of analyzed endometrial samples. It could be collected by biopsy, hysteroscopy or dilatation & curatage and if it possible PgR analysis should be done. Invasive procedures for collecting endometrial samples are hysteroscopy that permits evaluation of endometrial cavity and biopsy of suspicious lesion. The accuracy of hysteroscopy is high with sensitivity rate of 86.4% and specific rate of 99.2%, even higher in the diagnosis, than in excluding it. The possible dissemination of malignant cells through fallopian tubes during hysteroscopy, has not been proven in meta analysis in early stage of the disease. Obligate pretreatment assessments include biopsy, hysteroscopy or dilatation & curatage, radiologic imaging, contrast MRI (to exclude myometrial invasion, exclude extrauterine spread of disease, ovarian, lymphonodal, cervical involvement) even laparoscopy and assessment of ovaries, peritoneum and PW + SLN, as also CA 125, X ray for chests examination. The results according to many studies are that almost a two third of patients (50-75% of patients) that are treated with gestagen therapy have complete response, but 20-45% patients will have recurrence even after initial response and 25% would not answer on the therapy. Follow up is repeating of endometrial biopsies by hysteroscopy every 3 months which is recommended, until there is a complete response or achieving pregnancy. Surgery is recommended if there is no response after 6 months of medication treatment. Hormonal therapy that could be applied is progestins that inhibits the estrogenic effect and suppresses cell proliferation (medroxy progesterone acetate, megestrl acetate), GnRh analogues, but also local gestagens ( IUD), oral natural progesterons, aromatase inhibitors - antiestrogens as also three step endoscopic (hysteroscopic) resection - remove tumour, surrounding endometrium, myometrium.
Vasco Fonseca
Centro Hospitalar Lisboa Ocidental, Portugal
Title: Do breast cancer units treat patients based on their own neoadjuvant protocols?
Biography:
Vasco Fonseca has a degree in Medicine from the University of Lisbon in 2000. He is trained as a Medical Oncologist at the IPO of Lisbon and is currently working at the CHLO, in “Maria José Nogueira Pinto” Centre, as well as for the Portuguese National Military Forces. He is currently developing clinical trials in the area of breast cancer. He is the author of clinical protocol for Breast Cancer of the CHLO and has publications in reputed journals.
Abstract:
In the CHLO Breast Unit, which incorporates 4 hospitals, we treat almost 300 new breast cancer patients per year. In most cases, the international guidelines are very clear regarding locally advanced breast cancer, allowing a vast number of options in the grey area that concerns the Unit’s experience. We consider that the Unit’s experience and tumor staging, but also tumor biology, patient’s preference, individual risk factors and relative contraindications should be the principal considerations for the neoadjuvant treatment decision (according to international data). For this reason, we have formulated an internal protocol which allows us, not only to include all the indicated patients, but also to compile a database for their follow-up. In our protocol, triple negative, Her2 positive tumors and luminal B-like with high proliferative index, equal or above 2 cm (cT2N0), are proposed for neoadjuvant treatment. Patients with hormone dependent tumors that refuse surgical treatment, older patients, or patients with severe comorbidities, as well as selected luminal-A-like patients, are included in neoadjuvant hormonal treatment, which in some cases is extended over 8 months.
- Cancer Therapeutics | Cancer Nursing | Cancer Biology | Cancer Management & Prevention
Chair
Robert Thomas
Bedford and Addenbrookes Cambridge University Hospitals, UK
Co-Chair
Shanmugasundaram Ganapathy Kanniappan
Johns Hopkins University, USA
Session Introduction
Shanmugasundaram Ganapathy Kanniappan
Johns Hopkins University, USA
Title: Tumor glycolysis-The stygian link between two hallmarks of cancer and novel therapeutic opportunities
Biography:
Shanmugasundaram Ganapathy Kanniappan obtained his PhD degree from the University of Madras, India and underwent Post-doctoral training at the National Institute of Immunology (NII, New Delhi), University of California at Los Angeles (UCLA) and Johns Hopkins University (USA). Currently, he is an Assistant Professor at the Johns Hopkins University School of Medicine. He has been a recipient of Research Fellowship/Lectureship, (CSIR-UGC, India), a Concept Award (Department of Defense (DoD), USA), and a Pilot Research Grant (SIR, USA). He has several publications, and serving as an active Editorial Board Member and reviewer for prestigious journals.
Abstract:
Our understanding of aerobic glycolysis or tumor glycolysis popularly known as the Warburg effect has significantly advanced in the past two decades. Besides facilitating tumor growth and survival under unfavorable conditions, aerobic glycolysis also plays a pivotal role in therapeutic resistance. For example, the extracellular accumulation of lactate, a product of glycolysis impacts the tumor microenvironment (TME) and contributes to its low-pH and acidity. Noteworthy, TME acts as a barrier that blocks the efficacy of anticancer agents including chemotherapeutics and immune therapeutics. Furthermore, aerobic glycolysis has also been ascribed to support the immune-evasion of cancer. Thus, tumor glycolysis which is an integral component of the metabolic reprogramming (hallmark of cancer) is linked with immune-evasion (another hallmark of cancer). Using preclinical models, we demonstrated that deregulation of tumor glycolysis and/or the induction of metabolic stress sensitizes cancer cells to natural killer (NK) cell-cytotoxicity. Mechanistically, metabolic perturbation up-regulated the stress-inducible ligands that are recognized by specific NK cell receptors for further elimination. Notably, our recent data also show that sub-lethal, metronomic treatment with current, clinically relevant chemotherapeutics may also up-regulate such stress-inducible ligands indicating their sensitivity to NK cell mediated cytotoxicity. Taken together, these findings reiterate that cancer metabolism remains a viable therapeutic target which could be exploited for both chemo- and immunotherapies.
Qi-Fei Wang
The First Affiliated Hospital of Dalian Medical University
Title: Using 'zero-ischemia' and 'sutureless' techniques to implement laparoscopic partial nephrectomy with holmium laser
Biography:
Qi-Fei Wang has completed his Master’s degree from Dalian Medical University and is a PhD candidate at Tianjin Medical University. He is the Supervisor of Postgraduate students at the Dalian Medical University. He is a member of Rehabilitation Medical Association of Liaoning province China. He has published more than 12 papers in reputed journals.
Abstract:
Biography:
Adnan Yousif Rojeab has done his Doctorate in Electrical Engineering; he is a University Lecturer and Researcher. He has also worked at the Queen Mary University of London, University of West London. He is currently working at the London College. His research interests include action of electromagnetic fields on human system.
Abstract:
Cancer is a phenomenon of special reaction mechanism, which is functioning against the threat of severely acted tissues in the body. It is only created to eliminate severe damages and dangers that occur in the cells of the body, when the immune system fails to cure the damages. The effect of the cancer could only be ended when a direct, right and simple treatment method should be applied to cure the previous diseases that have caused the cancer, but not to attempt to treat the cancer itself. For the telomere matter, cancer cells have similar lengthening characteristics to those of germ cells. While in somatic cells, the telomere is shortening in every DNA replication. By applying a suitable amount and direction of a magnetic action on opposing the cancer cells, the lengthening of the telomere of the cancer could be inhibited, towards the somatic cells characteristics, and this application could be accepted as a method to treat cancer.
Robert Thomas
Bedford and Addenbrooke’s Cambridge University Hospitals, UK
Title: Lifestyle after cancer to reduce toxicity and improve outcomes – What evidence based strategies should we advise patients?
Biography:
Abstract:
As the chance of surviving, or achieving long term control, after cancer is improving, the number of people living with the consequence of cancer treatments at any one time is dramatically increasing. In the UK alone, this number has increased from two-three million in just five years. As consequences, the case for developing effective, self-help initiatives has never been stronger. This talk summarizes the international evidence, which proves that physical activity, nutrition and other lifestyle strategies can substantially reduce the risk of developing cancer, improve outcomes and ameliorate many of the long toxicities of consequences of biological therapies, chemotherapy and hormones and radiotherapy. These include fatigue, hot flushes, weight gain, arthritis, osteoporosis and mood disorders. This talk also highlights the underlying biological processes that take place in the body after a healthy lifestyle, which can have direct and indirect anti-cancer effects. By looking only at the scientific evidence, it breaks down the myths behind which foods to avoid and which to eat more of including nutritional interventions. It highlights the results of the world’s largest double blind randomized study of the National Cancer Research Network (NCRN) evaluation of a polyphenol rich nutritional intervention (The Pomi-T study). It emphasizes the potential risks and benefits of mineral and vitamin supplements to boost a healthy diet.
Sonia A Melo
University of Porto, Portugal
Title: Communication network mediated by exosomes as a new therapeutic target for pancreatic cancer
Biography:
Sonia A Melo has completed her PhD from the Faculty of Medicine of University of Porto and Post-doctoral studies from Harvard Medical School and MD Anderson Cancer Center. She is a Principal Investigator at I3S - Institute of Research and Innovation of the University of Porto and Institute of Molecular Pathology and Immunology of Porto University. Her career is fully committed to cancer research and has published more than 20 papers in reputed journals.
Abstract:
Cancer treatment experienced significant advance over the last years. This has been mainly due to therapy targeting of key biological mechanisms such as cell survival, proliferation, apoptosis, angiogenesis and, more recently, tumor immune response. Cell communication, however, despite playing a fundamental role in all steps of tumor progression, up to metastasis and therapy resistance, is still off the cancer therapy landscape. Hence, the major challenge of our work is to bring cell communication into the realm of cancer therapy. Exosomes, extracellular vesicles secreted by all cells, are key mediators of cell to-cell communication in cancer. We have identified a network of communication mediated by cancer exosomes in vivo, through the identification of their recipient cells. Additionally we show that targeting the most frequent pancreatic cancer exosomes communication route can be an effective target for pancreatic cancer therapy. Our strategy includes unique genetically engineered mouse models (GEMMs), which allow for the first time to trace exosomes in vivo and model therapeutic targeting of exosomes biogenesis. Our work demonstrates the in vivo significance of pancreatic cancer exosomes and opens a new avenue for groundbreaking discoveries in the treatment of pancreatic cancer and, eventually, other cancers.
Zofia Felicja Bielecka
Warsaw Medical University, Poland
Title: Protein expression profiling of sorafenib-resistant human renal cancer stem-like cells in three-dimensional in vitro model
Biography:
Zofia F Bielecka is a Medical Biotechnologist, currently working on tyrosine kinase inhibitors resistance in renal cell carcinoma. She is a PhD student at Warsaw Medical University, Poland (International School of Molecular Medicine). She is also a Research Assistant at Military Institute of Medicine in Warsaw, Poland and works in Laboratory of Molecular Oncology. She has gained considerable experience at the University of York, England and at the Lund University, Sweden. She has published 7 papers in reputed journals and has been serving a Reviewer in Elsevier journals. She is also a co-author of one patent application.
Abstract:
Primary-like resistance phenomenon to sorafenib (TKI) was previously observed in hypoxic conditions in two 3D models as well as in one 2D model in HKCSCs (human kidney cancer stem-like cells) cell line (Celprogen, cat no. 36117-44). Herein, we investigated the molecular background behind this phenomenon in 12 hypoxic total protein samples (each in triplicate) of renal cancer cells: primary HKCSCs resistant to sorafenib in hypoxia and other cell lines sensitive to sorafenib treatment in the same conditions: parental HKCSCs cell line, primary and metastatic renal cell carcinoma (RCC) cells from Memorial Sloan Kettering Cancer Centre (SK-RC-44 and SK-RC-45), metastatic RCC cell line (pleural effusion) ACHN cell line and HEK-293 cell line as a control. Additional control condition was untreated adequate cell lines in hypoxia. The acquired MS/MS data were pre-processed with Mascot Distiller software (v. 2.5, Matrix Science), and a database search was performed using the Mascot Search Engine (Matrix Science, Mascot Server 2.4.1) against the Swiss-Prot database restricted to human proteins. The results revealed potential candidates as elements of molecular mechanisms of primary resistance to sorafenib in renal cell carcinoma; those results will be further confirmed using Western blot analysis, possible confirming that apart from impact of hypoxia, the addition of targeted therapies alter signaling pathways in renal cancer cells, which means that mechanisms other than those involving hypoxia-inducible factors (HIFs) may be responsible for TKI-resistance.
Mahmood Faraz
Umea University, Sweden
Title: Identification and functional evaluation of LRIG1-interacting proteins
Biography:
Mahmood Faraz is a PhD student in Umea University, Sweden.
Abstract:
Carolina F Ruivo
University of Porto, Portugal
Title: ExoNet - Intratumor communication network mediated by exosomes in pancreatic cancer
Biography:
Carolina F Ruivo has completed her Master’s in Biomedical Engineering from IST, Lisbon in collaboration with University of Twente, Netherlands. Currently, she is working on a pre-doctoral project about the role of exosomes in tumor heterogeneity at Professor Sonia Melo’s Lab, Genetic Dynamics of Cancer Cells Group at University of Porto, Portugal.
Abstract:
Tumors are known to be heterogeneous, containing different cell types with distinct genetic and phenotypic features. Pancreatic cancer is a well-known example of tumor heterogeneity, showing a hierarchical organization of subpopulations with different tumorigenic potential. Intercommunication between tumor subpopulations is the key to development, progression and metastasis processes. Recent evidence shows that exosomes are important mediators of intercellular communication both at local and distant sites. If and how exosomes play a role in subpopulation communication is still unknown. In our work we have identified five subpopulations of pancreatic cancer cells based on cell surface markers which discriminate cells with different tumorigenic and self-renewal capacity. Using stable clones of cancer cells that express exosomes markers fused with fluorescent reporter proteins and secrete color-coded exosomes, we have studied the flow of exosomes between distinct subpopulations of cancer cells. Here we show that subpopulations of cancer cells communicate with each other via exosomes through an organized dynamic communication network (ExoNet). The presence of multicolor positive cells showed that exosomes are exchanged between different cancer cell subpopulations forming distinct routes of communication. The ExoNet reshapes in the presence of therapy to allow the tumor to respond and overcome the challenge. We have demonstrated that subpopulations of cancer cells communicate between them in a non-random manner using exosomes, and form a dynamic network of communication, which conveys the tumor with plastic properties that allows it to adapt in response to therapy.
Nuno Bastos
University of Porto, Portugal
Title: Intercellular communication mediated by exosomes as a new therapeutic target for pancreatic cancer
Biography:
Abstract:
Pancreatic cancer (PDAC) represents one of the most lethal cancers mainly due to a lack of reliable therapeutic options. Cell communication, in spite of playing a major role in tumor progression, is still off the cancer therapy landscape. Exosomes, extracellular vesicles derived from the endocytic pathway, are an important cell-to-cell communication system with neighbor/ distant cells. Our main aim is to study the role of exosomes biogenesis during PDAC progression and understand if cancer exosomes biogenesis could be a new therapeutic target in PDAC. Rab GTPases are crucial proteins in exosomes biogenesis and are involved in all stages of the endocytic pathway. We show that during PDAC progression Rab-5, -7, -27a and -27b are differently expressed. Increased expression of Rab-27a and -27b correlates with an increase in exosomes number, and these features are associated with a more aggressive phenotype. Additionally, when treated with, the standard care chemotherapeutic for PDAC, cancer cells change their exosomes biogenesis pattern, increasing exosomes release. Finally, we are using an inducible and conditional genetically engineered Rab27a knockout mouse model that spontaneously develops PDAC, to study the role of exosomes and its biogenesis in disease progression and therapy response, evaluating exosomes mediated communication as a new therapeutic option in PDAC.