Highlights from the New ACS Innovation Grants

Today we are highlighting the exciting work of several of our new innovation grantees that are part of the larger Summer 2025 grant slate. The full list of new Discovery Boost and Mission Boost grants can be found at the link above.

Mariella Filbin, MD, PhD
Dana-Farber Cancer Institute
Discovery Boost Grant

Project Title: “Investigating the Neuronal Regulation of Radioresistance in Diffuse Midline Gliomas”

This project is part of an emerging field of work known as “cancer neuroscience” which is studying how the reciprocal crosstalk between the nervous system and cancer cells influences malignant tumor growth. This project will investigate whether diffuse midline gliomas (DMG), an incurable form of childhood brain cancer, exploit interactions with surrounding normal neurons in order to develop resistance to radiation treatment. If successful, these experiments have the potential to transform our understanding of how the tumor microenvironment contributes to the development of radiation resistance in DMG (as well as other deadly brain tumors) and discover vulnerabilities hidden in neuron-glioma interactions to make radiation treatment more effective.

Edward Hinchcliffe, PhD 
University of Minnesota – Twin Cities
Discovery Boost Grant

Project Title: “Identifying Mitotic Histone H3.3 Phospho-Serine 31 Readers in Diffuse Midline Glioma Cells”

Diffuse midline gliomas are a leading cause of cancer deaths in children. Despite more than 200 clinical trials, no effective treatment exists, despite the long-established recognition of genetic mutations associated with the disease. This project will examine the biological mechanisms underlying how the K27M mutation affects the cell by analyzing the characteristics of tumor cells containing the genetic mutation and cells from the same patient where the mutation has been “corrected” using CRISPR gene editing tools.  Through this work, they will identify what other cellular “components” are affected by the tumor-causing mistake and will use this information unlock new diagnosis, biomarker, and treatment options for pediatric DMGs.

Murugesan Palaniappan, PhD 
Baylor College of Medicine
Discovery Boost Grant

Project Title: “Developing Allosteric Small-Molecule Inhibitors of CDK6/Cyclin D to Overcome Resistance in Breast Cancer”

Patients with advanced or metastatic estrogen receptor-positive (ER+) breast cancer are commonly treated with a combination of antiestrogen and cyclin-dependent kinase (CDK) 4/6 inhibitors. However, developing resistance to these therapies is very common, in part due to mutations in the active site of the kinases that result in weaker inhibitor binding. In this project, Dr. Palaniappan will use their DNA-encoded chemical library (DEL) screening technology to identify and validate novel small molecules that can bind elsewhere on the kinases to inhibit their function (a process known as allosteric inhibition). Successful completion of this project could rapidly advance a new drug for the treatment of CDK4/6 resistance in ER+ metastatic breast cancer patients who have become unresponsive to current therapies.

Jun Yan, MD, PhD 
University of Louisville
Mission Boost Grant – Stage II

Project Title: “Combining Irreversible Electroporation with Trained Immunity to Enhance Anti–PD-1 Therapy in Patients With Locally Advanced Pancreatic Cancer”

This Phase 2 clinical trial will assess the safety, tolerance, and efficacy of a novel pancreatic cancer therapy that combines irreversible electroporation, yeast-derived beta-glucan, and anti-PD-1 immunotherapy into a single treatment regime. Dr. Yan hypothesizes that induction of trained immunity by beta-glucan reprograms myeloid cells within the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment, thus promoting immunotherapeutic efficacy. This novel approach will be tested in locally advanced pancreatic cancer patients.

Yana Zavros, PhD 
University of Georgia
Mission Boost Grant – Stage I

Project Title: “Reprogramming the Tumor Microenvironment to Increase the Efficacy of Therapy in Pancreatic Ductal Adenocarcinoma”

Because the majority of pancreatic ductal adenocarcinoma (PDAC) patients are diagnosed at an advanced stage when surgery is not possible, there is a persistent need to develop non-surgical therapeutic approaches for the treatment of pancreatic ductal adenocarcinoma (PDAC). However, therapeutic resistance due to immunosuppression has been a recurring challenge. Dr. Zavros and team are using a bench-to-bedside-and-back-to-bench approach to study the fundamental underlying mechanisms of therapeutic resistance within the PDAC tumor microenvironment and to identify therapeutic approaches that can overcome tumor cell resistance.

Xiaoyu Zhang, PhD 
Northwestern University – Evanston Campus
Discovery Boost Grant

Project Title: “A Universal Approach to Drive the Immune Recognition of Cancer Cells”

In this project, Dr. Zhang will develop a universal strategy for harnessing the immune system to fight cancer. In this strategy, a special chemical group will be attached to covalent inhibitors that can induce the presentation of modified antigens on the surface of cancer cells, making it easier for the immune system to recognize them. If successful, this project holds immense promise for driving the immune recognition of cancer cells in a universal and generalizable manner, thereby overcoming the limitations of existing approaches and opening up new possibilities for cancer immunotherapy.