RFA: Yosemite-American Cancer Society Award

Grant Overview

The 2026 Yosemite-American Cancer Society Award supports innovative research to develop methodologies, establish feasibility, or pilot high risk/high reward projects to advance the prevention, diagnosis, or treatment of cancer as outlined below in either Topic #1 or #2. Preliminary data are not required. Priority will be given to projects that are highly innovative, feasible within a two-year maximum timeframe, and are poised to make an impact on cancer prevention, treatment, and healthcare delivery by demonstrating a plan of translation to the clinic.

Scientific Scope  

Topic #1 - Beyond the canonical proteome: post-transciptional and post-translational regulation in cancer

Non-genetic regulation beyond DNA sequence and mRNA abundance can profoundly shape tumor biology, yet remains underexplored. These layers include alternative splicing, RNA modifications, non-canonical translation (e.g., cryptic peptides), and post-translational modifications (PTMs) such as glycosylation. This topic seeks proposals that reveal or therapeutically exploit these regulatory mechanisms to advance cancer detection or treatment, leading to actionable biomarkers or therapeutic strategies.

Project proposals can include, but are not limited to:

• Mapping actionable proteoform landscapes (e.g., tumor-specific glycan signatures, PTM patterns, splice-isoform proteoforms).
  
  
• Exploiting altered glycosylation, PTMs, or splice-isoforms for therapy.
  
  
• Linking glycosylation states, PTMs, or isoforms to cancer-related mechanisms (e.g. immune evasion or therapy resistance).
  
  
• Identifying or targeting non-canonical translation products (e.g. cryptic peptides, UTR-derived or alternative ORF peptides) as biomarkers or therapeutic targets.
  
  
• Therapeutically modulating pathways governing post-transcriptional or post-translational regulation to overcome resistance or enhance treatment efficacy.

Topic #2 - Induced Proximity and New Frontiers in Protein Modulation

Induced proximity has introduced a transformative paradigm in medicine, originating with targeted protein degradation (i.e. PROTACs and Molecular Glue Degraders), and more recently expanding into a broader array of applications beyond degradation. Extending this paradigm to drive novel biological outcomes has the potential to unlock novel mechanisms of action and address targets previously considered undruggable. We seek innovative platforms, chemistries, and mechanistic strategies that leverage induced proximity or related concepts to modulate protein function, especially in ways beyond degradation.

Project may include but are not limited to:

• Strategies that leverage induced proximity between cancer-relevant proteins to achieve functional outcomes beyond degredation, such as selective killing, inhibition, activation, stabilization, relocalization, epigenetic editing, and more.
  
  
• Tools or methods enabling the discovery of proximity-inducing molecules, especially the discovery of molecular glues.
  
  
• Approaches that exploit spatial organization and higher-order assembly, (e.g. clustering of receptors or ligands on the cell surface).
  
  
• Proof-of-concept studies that use genetic tools (e.g. engineered protein control systems to manipulate protein states) to identify or validate target combinations for therapeutic induced proximity applications.
  
  
• Creation of entirely new modes of small-molecule action, including allosteric binders/modulators, conformation trapping, clustering-based activation, and other strategies that modulate proteins without engaging active sites. Projects should aim to reveal or engineer new mechanistic priniciples that expand the druggable proteome.

Eligibility

Investigators at any career stage with a full-time faculty (or equivalent) appointment at one of the invited institutions (see below) are eligible to apply.

Term and Budget

Yosemite-American Cancer Society Award grantees are funded at up to $300,000 direct costs for two-year projects, plus 10% indirect costs. The maximum allowable budget is $330,000 total costs. These grants are not renewable or transferable to a different institution. Applications should not exceed six pages (including one page for Specific Aims); this page limit does not include biosketches or references. Budgets submitted must be realistic estimates of the funds required for the proposed research.

Application Process

Applications must be submitted via ProposalCentral. The application instructions and policies can be downloaded from the ProposalCentral application portal.

Yosemite-ACS Award Policies

Yosemite-ACS Award Instructions