Johns Hopkins Scientists Receive $7.8 Million in Break Through Cancer Funding

The Johns Hopkins Kimmel Cancer Center and the departments of Gynecology/Obstetrics, Neurosurgery, and Pathology have received more than $7.8 million for new, multi-center projects designed to intercept and find cures for several deadly cancers, including breast cancer. pancreas, ovarian cancer and brain cancer. cancer known as glioblastoma.

The work is funded by the cancer research foundation Break Through Cancer as part of a three-year, $50 million effort for teams at five cancer research centers. The other centers are the Dana-Farber Cancer Institute in Boston; Memorial Sloan Kettering Cancer Center in New York; Koch Institute for Integrative Cancer Research at MIT, Cambridge, Mass. ; and the University of Texas MD Anderson Cancer Center in Houston.

We are grateful to Break Through Cancer for funding these innovative new avenues of research, which could help us find new treatments or new management approaches for some devastating cancers. We hope their model, combining the strengths of several leading comprehensive cancer centers, will produce exciting results. »

William Nelson, MD, Ph.D., Director of Johns Hopkins Kimmel Cancer Center and Chairman of the Board of Break Through Cancer

A project will study how to intercept ovarian cancer before it occurs. Many high-grade serous ovarian cancers — the most common and deadliest type of ovarian cancer — have been shown to originate in the fallopian tubes, explains Ie-Ming Shih, MD, Ph.D., director of the TeLinde Gynecologic Pathology Laboratory in the Department of Gynecology and Obstetrics and co-director of the Female Malignancies Research Group at Johns Hopkins Kimmel Cancer Center, and Rebecca Stone, MD, director of the Kelly Gynecologic Oncology Service, department of gynecology and obstetrics. Data released last month show that prophylactic removal of the fallopian tubes can significantly reduce the risk of ovarian cancer in the general population.

Because the fallopian tubes have no known vital function after women have finished childbearing, researchers will examine the safety and feasibility of extending fallopian tube removal as a primary cancer prevention strategy to women in the beyond those undergoing gynecological surgery. There is a tremendous opportunity to offer this to women during other planned abdominal surgeries, such as hernia repair or gallbladder removal. Investigators can then advocate for health insurance coverage of preventive fallopian tube removal and create educational materials for surgeons and patients.

Researchers will also work to create non-invasive imaging methods to improve and streamline the detection and harvesting of early cancerous lesions in the fallopian tubes; identify new biomarkers that can be used to advance ovarian cancer screening; and applying new technologies to detect and analyze pre-cancers. These include “OvaSeek”, a system for rapidly imaging fallopian tubes that have been surgically removed, and the “iCollector” for harvesting live cells from fallopian tube lesions. Additionally, the group will seek to compile an ovarian “precancer atlas” using molecular analyzes of tiny precancerous fallopian tube lesions obtained from participating cancer centers.

Other Johns Hopkins researchers on this project are Bert Vogelstein, MD, Clayton Professor of Oncology; Howard Hughes Medical Institute Researcher and director of the Ludwig Center for Cancer Genetics and Therapeutics, who will serve as research advisor on this project, Nickolas Papadopoulos, Ph.D., Tian-Li Wang, Ph.D., director of the Molecular Genetics Laboratory (MOLGEN) female reproductive cancer; Leslie Cope, Ph.D., a bioinformatician; and members of the MOLGEN laboratory.

The grant funds three additional lines of research:

Targeting minimal residual disease in ovarian cancer — A key factor underlying the low cure rates of ovarian cancer is the ability of chemotherapy-resistant cancer cells to persist after treatment. This minimal residual disease (MRD) is clinically undetectable and represents the “seed” that manifests as cancer recurrence. The main approach to slowing recurrence has been to put patients on so-called maintenance therapies – drugs to try to stop the cancer from coming back.

This project, led by Stephanie Gaillard, MD, Ph.D., Director of Early Phase Clinical Trials in Gynecological Cancer, Elana Fertig, Ph.D., Associate Director of the Cancer Center and Division Director of Quantitative and Co -director of the Convergence Institute; and Christopher VandenBussche, MD, Ph.D., aims to develop new capabilities to understand and target MRD. Researchers will study blood biopsies to detect minute levels of residual cancerous DNA in the blood after surgery is complete, and will use “second-look laparoscopies” – surgeries in which MRD cells can be harvested and studied – to study the properties of these cells. These investigations could uncover novel immune and targeted therapies for MRDs.

Additionally, the team will partner with pharmaceutical companies developing new therapies, using MRD as a clinical endpoint to be monitored. Finally, the team will develop and process laboratory models of disease that could be used to help predict which patients will or will not respond to new therapies.

Conquering KRAS in pancreatic cancer (in partnership with the Lustgarten Foundation) – The primary driver of pancreatic ductal adenocarcinoma is a mutation in a gene called KRAS. Many cells in the body need KRAS to function; however, several promising new therapies in development only target the mutant form of KRAS.

In this project, researchers will integrate clinical and laboratory approaches to understand why tumor cells become resistant to KRAS inhibition and how to use these new drugs in combination with other agents. The main objective is to develop effective combination therapy strategies to target KRAS in pancreatic cancer through preclinical studies and human clinical trials. The team will develop pharmaceutical partnerships to accelerate the translation of novel KRAS inhibitors into effective drugs.

The Johns Hopkins investigators working on this project are Nilo Azad, MD, co-director of cancer genetics and epigenetics; Jacquelyn Zimmerman, MD, Ph.D.; Elizabeth Thompson, MD, Ph.D.; Katrina Purtell, RN, Clinical Research Nurse Manager; Elana Fertig, Ph.D.; Associate Director of the Cancer Center and Director of the Quantitative Sciences Division and Co-Director of the Convergence Institute; and Hao Wang, Ph.D., associate director of the Quantitative Sciences Division and director of the Biostatistics Shared Resource.

Revolutionizing GBM Drug Development with Serial Biopsies — New therapies for glioblastoma have been delayed after the failure of several large phase III clinical trials. Most cancer treatments fail to penetrate the tumor due to the protective effect of the blood-brain barrier. Repeat biopsies have been used to evaluate promising oncology therapies for other types of cancer, but have not been considered for brain tumors due to safety concerns.

In this project, researchers will assess the safety and feasibility of a series of carefully performed biopsies. They will also work to evaluate blood and cerebrospinal fluid samples, called “liquid biopsies,” for molecular or other markers that indicate a cancer treatment is working. In addition, researchers will try to understand how the immune response is blocked by glioblastoma tumor cells.

The Johns Hopkins investigators working on this project are Chetan Bettegowda, MD, Ph.D., Jennison and Novak family professor of neurosurgery and vice chair of research for the department of neurosurgery; Matthias Holdhoff, MD, Ph.D.; Charles Eberhart, MD, Ph.D., director of neuropathology and ophthalmic pathology; and Jessica Wollett, Clinical Trials Manager.

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