California Archives - Page 9 of 22

Shari Bluband

OLE Health, St. Joseph Health Queen of the Valley (Queen of the Valley) and Adventist Health St. Helena (AHSH) are collaborating to nearly triple the number of OLE Health patients between the ages of 50 and 75 receiving colorectal cancer screenings and appropriate referrals to hospital partners for care navigation, additional testing and cancer treatment. Grant funding will enable the countywide consortium to develop and maintain a continuum of care for patients referred from OLE Health for further colorectal cancer diagnostics and care.

Robert Signer, Ph.D.

Funded in memory of Tony Smith, EdD, Member of the V Foundation Board, 2003-2017

Blood cancers, such as leukemia, often begin in the bone marrow where rare blood-forming stem cells regenerate normal blood cells throughout life. Many blood cancers can be eliminated with chemotherapy, but chemotherapy also destroys normal stem cells. Thus, many cancer patients depend on receiving stem cell transplants after therapy. Sadly, many patients are unable to receive life-saving transplants because of insufficient numbers of available stem cells. One way we can overcome this challenge is to develop ways to grow and expand blood-forming stem cells outside the body, but previous efforts to do so have been unsuccessful. Recently, we discovered that stem cells make new proteins much more slowly than other blood cells, and this slow rate of protein production is crucial for stem cell function. Proteins are the functional products of genes and perform many specialized tasks within cells. Making proteins too quickly increases assembly errors leading to the production of dysfunctional and toxic proteins. In contrast, producing proteins slowly helps ensure that new proteins are precisely assembled, are of high quality and function correctly. We found that growing stem cells outside the body increases the rate of protein assembly and decreases protein quality, which impairs stem cells. We are using new and innovative strategies to enhance protein quality within stem cells that could, for the first time, enable expansion of blood-forming stem cells in the laboratory. These discoveries could provide new therapeutic possibilities for numerous cancer patients.

Ling Li, Ph.D.

Each year, around 10,000 patients with Acute Myeloid Leukemia (AML) in the US will die from the disease. About a quarter of AML patients have a particular change in the FLT3 gene. This change leads to a lower chance of surviving the disease. This genetic change causes a FLT3 protein to be defective. Drugs such as tyrosine kinase inhibitors (TKIs) are used to treat the effects of abnormal FLT3 protein (FLT3-ITD). However, they are not very effective.

A particular type of cancer cells called leukemia stem cells (LSCs) is not removed by drugs like TKIs. Researchers think LSCs are responsible for the disease coming back in people with AML. Thus, LSCs with FLT3-ITD are considered responsible for resistance to TKI treatment. Understanding why LSCs are resistant to TKIs will allow us to target these stem cells, and possibly cure people.

FLT3-ITD signals can be changed by modifying the protein in different ways such as methylation. Our studies found a link between methylation of FLT3-ITD and LSC resistance to TKI treatment. Thus, we think that FLT3-ITD methylation helps these stem cells resist drug treatment. We want to understand better how methylation helps LSCs survive. Also, we will test whether a lower amount of methylated FLT3-ITD protein leads to fewer cancer stem cells in test animals. Targeting protein methylation could lead to new ways to treat people with FLT3-ITD leukemia.

Stephanie Correa, Ph.D.

Funded by the Stuart Scott Memorial Cancer Research Fund

Tamoxifen is an estrogen-like drug that is used to treat breast cancer patients, breast cancer survivors, and patients with a family history of breast cancer. As a treatment, tamoxifen is extremely effective at decreasing the changes of getting cancer and increasing patient survival. Unfortunately, tamoxifen also causes negative side effects such as hot flashes and bone loss. Because of these concerns, up to a quarter of all patients fail to complete the treatment. The goal of our research is to understand how tamoxifen can cause hot flashes and bone loss. We will use genetically engineered mice to identify the brain regions that mediate the effects of tamoxifen on temperature control and bone density. We will also use cutting-edge molecular tools to determine precisely how these brain regions are affected by tamoxifen. To model the treatment conditions in humans, our studies use females of reproductive age and a long-term treatment using the same dosage given to humans. In the end, our studies will identify the specific areas that are responsible for the negative effects of tamoxifen. This information will help us design and begin to test strategies for alleviating hot flashes and/or bone loss in patients. Any treatments that provide relief from the side effects of tamoxifen will increase patient quality of life, increase the chances that patients will complete their treatments, and ultimately save lives.

Judith Varner, Ph.D.

Great strides have been made toward finding cures for cancer, which is expected to strike 1.6 million Americans this year. Although many cancer patients still die from their disease, the overall cancer death rate is declining due to improved detection methods and novel therapies. The exciting development of immune therapy has shown that activating a patient’s own immune system to attack and kill cancer cells can lead to cancer cures and improved life spans for patients with many forms of cancer. However, there are still many patients whose tumors are resistant to immune therapy. We recently found that tumor associated macrophages, immune cells that are found in great numbers in tumors, cause resistance to immune therapy. We identified new drugs that break this resistance to immune therapy; these drugs led to cures in animals with cancer. We will test these drugs in patients with head and neck squamous cell carcinoma, monitoring for changes in biomarkers of immune suppression and tumor progression. We will also identify new immune therapy drug combinations that can improve cancer care. These studies will contribute to the development of novel, effective immune therapies for cancer patients.

Guido Marcucci, M.D.

Acute myeloid leukemia (AML) is a devastating cancer of the bone marrow resulting in progressive accumulation of leukemia cells and rapidly leads to bone marrow failure and death if not timely treated. In 2016, 20,000 new cases of AML and 10,000 disease-related deaths occurred in the United States alone. The median age at diagnosis is 67 years and the incidence of the disease increases with aging of the population. Estimated survival for AML patients diagnosed in the last 5 years in US is only 26.6%. Since 1969 only 5 drugs has been approved for treatment of AML. Therefore there is a clear unmet need for new and more active drugs. The current view is that AML treatment resistance or disease reoccurrence is due to the inability of current chemotherapy and/or molecular targeting drugs to eliminate the leukemia stem cells (LSC). These primitive malignant cells are capable of initiating and maintaining leukemia and are most resistant to current treatments. Here we propose to target and eliminate LSC by harnessing the immune system with newly synthesized bispecific antibodies and engineered T-cell cells aimed at IL1RAP, a protein that is preferentially expressed in LSC. Both these products are already in our hands and have a strong antileukemia activity and the ability to reduce LSC burden. Leveraging the infrastructure for drug development (including manufacturing facilities) already present at our Institution, we propose to complete preclinical, pharmacokinetic and pharmacodynamic studies and prepare for toxicology studies in order to move these products rapidly into the clinic.

Kimberly Kirkwood, M.D.

Pancreatic cancer is highly lethal. Successful treatment may be possible if the cancer is identified early, but most pancreatic cancers are not caught until they have spread. Some pancreatic cancers start off as cysts, or fluid-filled sacs. Not all pancreatic cysts are cancerous though. It is easy to see pancreatic cysts using imaging tools like MRI, and to collect fluid from them using a biopsy procedure. However, we currently don’t have any good tests to determine which cysts are likely to become cancerous. We think the necessary information may lie in proteins contained in the pancreatic cyst fluid.  Our project aims to create a test that will analyze the fluid to identify which cysts are cancerous and which are benign. By finding cancerous pancreatic cysts at an early stage, before they spread, we expect to be able to improve survival for patients. Our project will also help patients with benign cysts to avoid risky and expensive surgery. We also expect to learn more about the ways these special proteins play a role in the development of cancers in other bodily organs.