Grant Archive - Page 40 of 141

Pavani Chalasani, MD

Funded by Hooters of America, LLC

The goal of “Campaign to Improve Access to Clinical Trials” at the University of Arizona Cancer Center (UACC) is to increase the clinical trial access to a diverse population in Arizona. Dr. Chalasani, Breast Cancer Disease Oriented Team Leader, will oversee the campaign to improves access by involving the breast multidisciplinary team, patient navigators and physician liaisons to develop educational materials and outreach programs. Patients and community physicians will be targeted through proposed outreach programs by developing targeted educational materials. Materials and training will be provided to introduce and educate about clinical trials to patients early by various members of their cancer team. The goal of this campaign is to become a model for other disease teams and cancer centers to implement to improve clinical trial enrollment.

Adam Bass, MD

Funded by Gastric Cancer Foundation

This application focuses upon the need to develop new therapies for stomach cancer, which is the 3rd leading cause of cancer mortality in the world.  In our laboratory’s prior studies, we described the patterns of disruptions in the genome (or DNA of the cell) that develop in the stomach cells which become cancerous.  The overall hope for this work is that finding the genetic causes of cancer can be a source of development of new targets for guiding cancer therapy.  The primary way to try to use genomic understanding of cancer to guide therapy has been to find specific genes which are aberrantly activated in cancer.  However, to date, approaches to use this approach to guide therapy for stomach cancer has been largely disappointing despite individual successes.  Therefore, this new research program supported by the V Foundation and the Gastric Cancer Foundation aims to develop alternative approaches to use our understanding of the gastric cancer genome to guide development of new therapies.  Instead of focusing on the genomic alterations that impact individual genes, we are now pivoting to more broadly evaluating the patterns of genomic alterations and the classes of instability or genomic disruptions that occur in cells.  We have developed new approaches to classify the types of genomic disruptions that are characteristic of gastric cancer and then directly connecting these patterns to possible new therapeutic targets.  We believe that this work may serve as a critical foundation for novel development of therapies for these deadly cancers.

Timothy Yap, MD, PhD

Funded by Lloyd Family Clinical Scholar Fund

The term DNA damage response (DDR) inhibitors is used in cancer treatment to refer to a group of drugs, which block important processes that cancers rely on to repair their DNA. While PARP inhibitors (a type of DDR inhibitor) are approved, they do not benefit all patients, and their effects are not long-lasting. Combining PARP (or other DDR inhibitors) with drugs that may boost their effects is a promising approach, which has been shown in laboratory studies (cancer cells or animal testing) to be more effective than each drug given alone. My program of DDR inhibitor combination trials aims to benefit patients with cancers with defects in DDR and other important processes by matching them with suitable DDR inhibitors in combination with carefully selected drugs, therefore personalizing cancer treatment for each patient. Multiple new and promising DDR inhibitor combinations will be tested. Trials not well-tolerated or effective will be stopped early, while trials with promising combinations will be increased in size. We will personalize these treatments for each patient by studying their cancer/blood samples to ensure that the genetic defects of the tumor match the combination treatment, so as to increase the chance of success. If patients stop responding to treatment, they will be allowed to switch to a different DDR inhibitor combination guided by fresh analyses of new cancer/blood samples. This program of trials aims to advance our DDR scientific knowledge, improve outcomes for each patient and guide future trials in order to get better treatments approved.

Alice Bertaina, MD, PhD

Funded by Lloyd Family Clinical Scholar Fund

Leukemia is a cancer that starts in blood-forming cells found in the bone marrow. It is the most common cancer in children and teenagers, accounting for almost 1 out of 3 cases. Despite recent advances in the treatment of childhood leukemia, a substantial proportion of patients are resistant to conventional treatments. For these children, the probability of cure is very low (<30-50%). The best treatment for leukemia patients, especially those who have not responded to other therapies, is stem cell transplant, but the application of this life-saving treatment has been traditionally limited by a lack of suitable donors. The lack of suitable donors is a particular problem in African American or mixed heritage populations because finding a matched donor is less likely in these populations. We have developed a stem cell transplant strategy that greatly increases the number of patients who can receive transplants. However, this strategy cannot provide the critical anti-leukemic and infection fighting functions required to kill all the leukemic cells and is therefore unable to give patients who receive transplants long term cancer-free outcomes. In this project we will perform three clinical trials designed to test the safety of three innovative cell therapies, which, when given in conjunction with our stem cell transplant strategy, have the potential to fight leukemia. Our ultimate goal is to identify the optimal anti-leukemic cell product that improve cancer-free outcomes for children with leukemia.

Zhaoming Wang, PhD

Supported by Bristol-Myers Squibb through the Robin Roberts Cancer Thrivership Fund

Survivors of childhood cancer are at high risk of late health problems related to cancer treatment. Our early work suggested that health problems differ among survivors based on social-economic status like level of education, household/personal income, and the neighborhood in which they live. In the proposed research, we will describe and measure differences in health problems among childhood cancer survivors based on the social-economic status. We will focus on common health problems including obesity, high blood fat levels (triglycerides or cholesterol), abnormal blood sugar control, high blood pressure, heart muscle weakness, and heart attack. We will use stored blood samples and data already available from the St. Jude Lifetime Cohort Study to study biologic changes that may predict a survivor’s risk of health problems and links to social-economic factors. We hope that the results of this work will help identify survivors at higher risk for health problems and guide new research aiming to reduce, reverse, or prevent the harmful effects of social-economic factors on health problems after treatment for childhood cancer.

Ulrike Peters, PhD

Supported by Bristol-Myers Squibb through the Robin Roberts Cancer Thrivership Fund

Colorectal cancer starts in the large intestine. It is the second leading cause of cancer death in men and women in the US. Alaska Native people have among the highest rates of colorectal cancer in the world. Alaska Native people also die more often of this disease than any other racial or ethnic group in the US. The reasons for these health disparities are not fully understood.

Almost no research exists on molecular changes in Alaska Native colorectal cancer tumors. In this study, we will look at the genes expressed in these tumors. Genes code for proteins which support normal cell function. Changes to genes may result in abnormal growth of the cells resulting in cancer. Studying gene expression tells us which genes in the tumor may be causing the cancer and will help us understand more about the patterns of gene expression among Alaska Native colorectal cancer patients. We will also examine if tumor gene expression can tell us which patients will live longer with their cancer.

This research will help to identify colorectal cancer patients with aggressive disease at diagnosis. This could help to guide clinical decision making and improve disease outcomes. Also, this research may tell us if Alaska Native colorectal cancer patients might benefit from available or new treatments.

Jennifer Doherty, PhD, MS

Supported by Bristol-Myers Squibb through the Robin Roberts Cancer Thrivership Fund

Ovarian cancer is a leading cause of cancer death among US women, with about 50% of women dying from their disease within five years. Treatments including surgery and chemotherapy are meant to cure the cancer, but in about 50% of women, the cancer will come back.

Black and Hispanic women are more likely to stop treatment early, and to die from their disease than non-Hispanic white women. These differences are referred to as race/ethnic disparities. There are many reasons for disparities, including differences in access and quality of medical care. Black and Hispanic women are also more likely to have other health conditions (i.e. comorbidities), like heart disease or diabetes, when they are diagnosed with ovarian cancer. These comorbidities may change a patient’s ability to tolerate treatment, and in turn, may reduce their survival. Comorbidities may also change the biology of the tumor. Looking at tumor markers may provide information on response to treatment and survival of the patients.

The goal of this project is to understand race/ethnic disparities in ovarian cancer treatment, recurrence, and mortality. In this project, we will examine how comorbidities and tumor markers differ in a diverse group of ovarian cancer patients. This study will take place using data from the Kaiser Permanente Healthcare system. This research project will provide information for doctors about how health conditions can affect a woman’s response to treatment, so that she can get better cancer care, and help to reduce disparities in ovarian cancer treatment and outcomes.

Shannon Stott, PhD

Nick Valvano Translational Research Grant *

Brain tumors are the number one cause of pediatric cancer deaths. And despite advances in treatment, children in remission have both the constant worry of their tumor returning, plus long term (often delibitating) treatment-induced side effects. . As new treatments are developed, there is an urgent need to better monitor treatment response.

Due to their location, the most common tool for monitoring pediatric brain tumors is recurrent imaging ( such as a series of MRI imaging scans over time). While imaging can provide some information about current disease status in brain tumor patients, it can’t provide details on how the tumor has changed in response to therapy. To address this gap in technological capacity, our team has developed a less invasive blood test that can remove rare tumor cells and particles released by the tumor in brain tumor patients. This test requires less than a teaspoon of blood, which makes it ideal for pediatric patients. For this study, we will use our test on 60 pediatric cancer patients with gliomas and medulloblastomas, in order to detect and monitor the these biomarkers in the blood, and watch for changes to their levels throughout treatment. At the end of this study, we then plan to test our techology in multi-center clinical trials. Our long-term goal is to use tumor biomarkers in blood to more rapidly identify when brain cancer patients need to be retreated, which we hope can in turn be used to accelerate and improve therapeutic interventions.

Jun Qi, PhD

Co-funded by the Dick Vitale Gala, and WWE in honor of Connor’s Cure

Dr. Jun Qi is a synthetic organic chemist and chemical biologist who has developed small molecules and pioneered a novel chemical strategy in which small molecule therapeutics can be designed to destroy specific proteins within a cell, as opposed to suppressing enzymatic function. Dr. Mariella Filbin is a physician scientist specializing in pediatric neuro-oncology with clinical and scientific interests converging upon pediatric brain cancers, in particular, diffuse intrinsic protein glioma (DIPG) which is universally fatal. Dr. Filbin has used patient-derived models to identify a potential DIPG-specific target for Dr. Qi’s protein degrader technology. They will work together to overcome challenges in childhood brain cancer treatment, such as toxicity and blood-brain-barrier (BBB) penetration. This exciting study has two broad objectives:

To define the mechanism by which the cancer dependent protein is driving DIPG formation and growth;
To yield optimized drug compounds suitable for preclinical study and translation to clinical trials in DIPG.

By working together as team, Drs. Qi and Filbin will cultivate a symmetrical relationship in which chemistry will be used to clarify the biology; and biology will be used to guide the small molecule design and development. By combining their complementary skill sets in chemistry, chemical biology and cancer biology, their joint efforts will result in the preclinical validation of eliminating the target genes and ideally the development of a clinical trial using this novel strategy for DIPG to achieve the bench-to-bedside translation of their research.

Christine Pratilas, MD

Bob Bast Translational Research Grant *

RAS is a gene that plays a major role in cancer. The three members of the RAS family are HRAS, NRAS, and KRAS. One of these genes is mutated in about 15% of cancers. The mutant form is hyperactive.
In pediatric solid tumors, RAS is mutated in about 1-3% of cancers and more often in rhabdomyosarcoma.
Inhibiting RAS activity has been a difficult task in cancer drug development. One type of drug, the farnesyl transferase inhibitors (FTI), were developed twenty years ago. Clinical trials using these drugs were disappointing. We now have a better understanding of how to select patients that will best respond to FTI.
Only mutant HRAS is dependent on the farnesyl transferase enzyme. So, FTI should work best in patients with HRAS mutant cancers.
In a clinical trial of patients with HRAS mutant head and neck cancer, patients were treated with tipifarnib, an FTI. Trial outcomes showed that patients’ tumors got smaller (responded).
We are now studying FTI in pediatric solid tumors. We want to know what adaptive events occur in the cell and whether these changes only occur in mutant HRAS tumors. We also want to learn how tumors may escape the anti-cancer effects of FTI.
Studying these changes and paths of resistance can help us develop more complete and lasting responses. Our study aims to address these issues to find effective treatments for patients with HRAS mutant cancer.