Researchers develop new nanoparticle to boost immune system
Vanderbilt researchers have developed a new nanoparticle that can more effectively get drugs inside of cells to boost the immune system and fight diseases like cancer.
Featured Speakers:
Alan Ashworth, PhD, FRS
(UCSF Helen Diller Family Comprehensive Cancer Center)
is the President of the Helen Diller Family Comprehensive Cancer Center at University of California, San Francisco and Senior Vice President for clinical services, UCSF Health. Dr. Ashworth was a key member of the team that discovered the BRCA2 gene in 1995, which is linked to an increased risk of breast, ovarian and other cancers. In 2005, his lab identified a way to exploit genetic weaknesses (using synthetic lethality) in cancer cells with mutated BRCA1 or 2 genes, leading to a new approach to cancer treatment, PARP inhibition. Four different PARP inhibitors have now been approved by the FDA for the treatment of ovarian, breast, pancreatic and prostate cancer based on this observation, which was named by Nature in the top 20 discoveries in cancer in the 21st century. He continues to develop new treatments for cancer using genetic principles.
Judy E. Garber, MD, MPH
(Dana Farber Cancer Institute)
is the Susan F. Smith Chair and Chief of the Division of Cancer Genetics and Prevention at Dana-Farber Cancer Institute and a Professor of Medicine at Harvard Medical School. She conducts research in clinical cancer genetics, with a special focus in the genetics of breast cancer. Dr. Garber is also a leader in research into the characteristics and treatment of triple negative breast cancer, the most common form in women with BRCA1 mutations and an expert in Li-Fraumeni Syndrome. Her translational research focuses on the evaluation of novel agents targeting DNA repair defects in breast cancer, including PARP inhibitors for treatment and prevention of breast cancer and other BRCA-associated cancers, and the study of other agents for reduction of breast cancer risk.
Padma Sheila Rajagopal
(National Institute of Health, Cancer Data Science Laboratory)
is a recipient of the Ruth L. Kirschstein F32 Postdoctoral Fellowship and the American Society of Clinical Oncology / Breast Cancer Research Foundation Conquer Cancer Young Investigator Award for her research on integrating germline variants through a predicted transcriptome model of the breast and comparing prognostication of outcomes in breast cancer to the tumor transcriptome. She joined the Cancer Data Science Laboratory as an Assistant Clinical Investigator in 2021. Dr. Rajagopal’s laboratory currently investigates how genomic and transcriptomic interactions between germline variants / inherited cancer syndromes and somatic development in tumors can improve clinical prediction and prognostication in patients with cancer.
Bert Vogelstein, MD
(Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins)
is the Clayton Professor of Oncology and Pathology, An Investigator of the Howard Hughes Medical Institute, and a Director of the Ludwig Institute and Lustgarten Dedicated Laboratory for Pancreatic Cancer Research at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Dr. Vogelstein and his colleagues discovered the genetic basis of human colorectal tumors. In the process, they discovered many of the genes, pathways, and concepts that are the foundation of modern cancer research. His group's basic scientific studies have been distinguished by a focus on practical applications of the knowledge gained from their work. For example, Vogelstein and his colleagues not only participated in the discovery of the genetic bases for hereditary colorectal cancer predisposition syndromes in the 90's, but a more recently developed an effective form of therapy for one such syndrome that is based on understanding of its genetic defect. From a broader perspective, his group initiated a new chapter in diagnostics in 1992 when they demonstrated that somatically acquired driver gene mutations can be used as biomarkers for cancer. This approach is now often referred to as "liquid biopsies". His group currently focuses on developing new approaches to detect cancers earlier as well as developing novel immunotherapeutic agents that can combat cancer if it is not detected early enough.
This is an international phase III trial, with a Bayesian design, incorporating two sequential randomisations. It efficiently examines a series of questions that routinely arise in the sequencing of treatment. The study design has evolved from lengthy international consultation that has enabled us to build consensus over which questions arise from current knowledge and practice. It will enable potential randomisation for the majority of patients with inguinal lymph node metastases and will provide data to inform future clinical decisions.
InPACT-neoadjuvant patients are stratified by disease burden as assessed by radiological criteria. Treatment options are then defined according to the disease burden strata. Treatment is allocated by randomisation. Patients may be allocated to one of three initial treatments:
A. standard surgery (ILND); B. neoadjuvant chemotherapy followed by standard surgery (ILND); or C. neoadjuvant chemoradiotherapy followed by standard surgery (ILND).
After ILND, patients are defined as being at low or high risk of recurrence based on histological interpretation of the ILND specimen. Patients at high risk of relapse are eligible for InPACT-pelvis, where they are randomised to either:
P. prophylactic PLND Q. no prophylactic PLND
This phase IV trial evaluates how well giving standard of care (SOC) peptide receptor radionuclide therapy (PRRT) after SOC surgical removal of as much tumor as possible (debulking surgery) works in treating patients with grade 1 or 2, somatostatin receptor (SSTR) positive, gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have spread from where they first started (primary site) to the liver (hepatic metastasis). Lutetium Lu 177 dotatate is a radioactive drug that uses targeted radiation to kill tumor cells. Lutetium Lu 177 dotatate includes a radioactive form (an isotope) of the element called lutetium. This radioactive isotope (Lu-177) is attached to a molecule called dotatate. On the surface of GEP-NET tumor cells, a receptor called a somatostatin receptor binds to dotatate. When this binding occurs, the lutetium Lu 177 dotatate drug then enters somatostatin receptor-positive tumor cells, and radiation emitted by Lu-177 helps kill the cells. Giving lutetium Lu 177 dotatate after surgical debulking may better treat patients with grade 1/2 GEP-NETs
Vanderbilt nanodrug may be a paradigm shift for cancer
A multidisciplinary research team at Vanderbilt University and Vanderbilt University Medical Center has discovered a new way to kill a tumor by disrupting its acidic microenvironment without harming normal tissue.
This phase Ib trial tests the safety and tolerability of ZEN003694 in combination with an immunotherapy drug called pembrolizumab and the usual chemotherapy approach with nab-paclitaxel for the treatment of patients with triple negative-negative breast cancer that has spread to other parts of the body (advanced). Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Immunotherapy with monoclonal antibodies, such as pembrolizumab may help the body's immune system attach the cancer and may interfere with the ability of tumor cells to grow and spread. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Combination therapy with ZEN003694 pembrolizumab immunotherapy and nab-paclitaxel chemotherapy may help shrink or stabilize cancer for longer than chemotherapy alone.
