Cancer Stem Cells
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studying mechanisms of therapy resistance in cancer cells
Solid cancer tumors
Solid tumors is a result of abnormal cell proliferation in soft and hard (calcified) tissues, but not all tumors are cancer. Cancer cells are capable of leaving organs of their origin, circulating in the blood stream, and colonizing in the distant tissues such as lymph nodes, lung, or liver. Multiple studies on various types of solid tumors (e.g., breast, brain, prostate, colon, pancreatic, ovarian, lung), and hematologic cancers provided experimental evidence of existence of cancer stem cells that initiate tumor growth when transplanted and re-transplanted into experimental animals (xenotransplantation), while other tumor cells lack the de novo tumorigenic capacity. The tumorigenic cancer cells are long-lived due to self-renewal, a cell division typical for normal stem cells. They also exhibit stem cell-like properties making them resistant to apoptosis, chemotherapeutics, radiation, and immunotherapies. Cancer stem cells (CSC) can be fast or slow dividing. Slow-dividing or dormant CSCs are linked to cancer relapses, while fast-proliferating CSC are associated with refractory to therapies in primary tumors.
hematological cancers
Blood is a liquid tissue of the circulatory system. Due to blood cells’ mobility and relative accessability, hematopoietic stem cells were the first characterized adult stem cells. Genetic and epigenetic aberrations in blood stem and progenitor cells cause various types of proliferative and differentiation disorders including hematologic malignancies. The hierarchical model of normal hematopoiesis, picturing a self-renewing stem cell producing differentiated progenies on the top of the hierarchy, is applicable to both hematologic, co-called liquid, and solid tumors. According to this model, a small fraction of self-renewing cancer stem cells is a source of non-self-renewing tumor cells with altered proliferation and differentiation. The stochastic model of cancer postulates an equal role of tumor cells in maintaining neoplasms through their capacity of obtaining or re-gaining self-renewal. This phenomenon, known as cancer cell plasticity, and intra-tumoral heterogeneity underlie cancer resistance to therapies and relapse.
Fighting pediatric cancers
Four Diamonds Foundation Mission
The Four Diamonds mission is to conquer childhood cancer by assisting children and their families through superior care, comprehensive support and innovative research.
Four Diamonds has assisted 100 percent of the childhood cancer patients who have been treated at Penn State Children’s Hospital.
FOUR DIAMONDS PEDIATRIC CANCER RESEARCH CENTER GOALS
Conduct clinical trials that leads to new treatments and drugs
Offer treatment and hope to patients whose disease is not responding to therapy
Foster collaboration with doctors and scientists around the world
Train researchers so we can continue to fight for the next generation
Focus on translational research
Dr. Sinisa Dovat, MD is a pediatric hematologist-oncologist, the Vice Chair of Basic Science Research, and the Director of Translational Research in the Pediatric Experimental Therapeutics Program at the Department of Pediatrics. Dr. Dovat employs the consolidation strategy for efficient implementation of basic research discoveries, the pre-clinical cancer research, to clinical trials of the most promising anti-cancer drugs developed at the department of Pediatrics. As a Translational Research Program Director, Dr. Dovat orchestrates therapies’ assessment using complementary in vitro and in vivo models such as patient-derived xenografts (PDX), human induced pluripotent stem cells (hiPSCs), and cancer cell lines investigated with the genome editing and chemical libraries screens.
NEUROBLASTOMA research
Neuroblastoma is a solid cancer of the nerve tissue of the sympathetic nervous system. It usually begins in the adrenal glands, but may originate in the chest, near the spine in the neck, or in the spinal cord. Most of neuroblastoma cases are diagnosed before age of 5. Neuroblastoma is a very rare but highly aggressive disease with about 70% of cases progressing to metastatic disease. Amplification of MYCN oncogene is one of the most common genetic factors associated with neuroblastoma. Other neuroblastoma-specific alterations include a deletion of the 1p36 chromosome region and gain of genetic material on 17q. Familial neuroblastoma is caused by rare germline mutations in the ALK, PHOX2B, and KIF1B genes.
Expression patterns of immune genes reveal heterogeneous subtypes of high-risk neuroblastoma
A recent study conducted at the Department of Pediatrics by Zhenqiu Liu, HG Wang, and other co-authors, identified the four genes (ADAM22, GAL, KLHL13 and TWIST1) up-regulated in MYCN amplified neuroblastoma. To learn more click here.
Neuroblastoma Group
Dr. Hong Gang Wang, PhD laboratory aims to better understand the fundamental mechanisms that control apoptosis and autophagy in the context of oncogenesis with the ultimate goal to translate basic science discoveries to the development of new approaches for the treatment of cancer. Dr. Wang initiated a neuroblastoma group at the Department of Pediatrics to consolidate effort for understanding neuroblastoma pathogenesis and development new drugs.
Penn State Cancer Institute Research Groups and Clinical Trials
Penn State Cancer Institute and College of Medicine conduct research programs dedicated to generation of Next-Generation Therapies, understanding Mechanisms of Carcinogenesis and Cancer Control. Initiated by physicians and research scientists, several focus groups work on creating efficient treatments against solid cancers and hematologic malignances.
Learn more about research groups and clinical trials here
Patient-Derived xenograft core
our team
Dr. David Claxton has longstanding interests in leukemia biology and therapeutics. Acute myeloid leukemia and related disorders are his principal foci. Leukemia therapeutics are particular interests, including drug development and clinical studies, blood and marrow transplantation, and clinical supportive care. He has a laboratory which has banked many samples of human leukemia and lymphomas. These are viably cryopreserved, used in studies and available to collaborators.
Dr. Arati Sharma’s research is focused on melanoma, the most aggressive and metastatic form of skin cancer, and leukemia. As a principle investigator and a director of PDX core, Dr. Arati Sharma leads and actively participates in many preclinical and clinical studies including collaborative projects with the department of Pediatrics.
Dr. Melanie A. Ehudin is a post-doctoral fellow with an extensive chemistry background and a genuine interest in the field of a comparative medicine. Melanie is passionate about learning about similarities and differences in biology among animal species and understanding of mechanisms of human and animal disease.
About The Clinical and Preclinical Core for the Program Project Grant
The Clinical and Preclinical Core for the Program Project Grant includes AML repository, AML PDX, other AML animal models, and testing AML therapeutics in pre-clinical and clinical trials.
PIs: Drs. Claxton and Sharma
Penn State Institute for Personalized Medicine
Penn State Institute for Personalized Medicine gives scientists the tools to develop research and future therapies for patients
Dr. Yuka Imamura, PhD
Dr. Yuka Imamura is an Associate Professor, the director of Genome Sciences Center with a profound expertise in genomics, oncology, and immunology. Dr. Imamura, an active member of SCRBP and other programs at Penn State College of Medicine, brings bright ideas and people together to accelerate basic and translational research at Penn State College of Medicine.