# Molecular and immunologic evolution of melanomas from pre-neoplastic lesions

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $951,000

## Abstract

Project Summary/Abstract
Tremendous advances in the molecular analysis of melanomas and their immune microenvironment
have provided mechanistic insights, which in turn have translated into remarkable improvements to
treat and even cure patients with advanced disease. However, many patients still succumb to their
disease, in part because treatment starts too late. Identifying patients in need of systemic treatment
earlier and removing pre-neoplastic lesions before they evolve into cancer are promising effective ways
to reduce melanoma-related deaths. Current screening methods can detect lesions with a broad
spectrum of natural behavior-- from those with lethal potential to the completely benign. There is an
urgent need to develop precision molecular tests to:
 (1) Distinguish between benign and malignant lesions (i.e., diagnostic biomarkers);
 (2) Differentiate biologically indolent versus aggressive tumors in need of additional treatment
 (i.e., prognostic biomarkers);
 (3) Identify high-risk individuals who should be screened (i.e., screening biomarkers).
My group is performing multi-omics studies on primary lesions to study the earliest molecular and
cellular events associated with melanoma initiation and evolution to obtain key insights that are
essential to improve risk stratification of early stage cancers, cancer prevention and detection.
Characterizing the genetic evolution of main melanoma subtypes as they develop from their respective
pre-neoplastic lesions is one major goal of this proposal, as is developing a biomarker-based taxonomy,
which will serve as framework for developing significantly advanced diagnostic and prognostic
algorithms. Studies of the tumor genome will be complemented by characterization of the composition
and functional state of immune cell infiltrates during melanoma evolution to shed light on the interaction
between the immune cell infiltrate and tumor cells. The combined analysis of tumor genomes and host
response will reveal key mechanisms driving elimination, equilibrium, and ultimate escape and allow
us to extract biomarkers, which will undergo validation in patients with known outcomes with the goal
to develop clinically sound tests. Specifically, we will formulate candidate algorithms that can (i) better
anticipate metastatic dissemination than current methods and (ii) predict whether a pre-neoplastic
lesion is likely to progress to melanoma, and validate them using patient cohorts with known follow-up
information.

## Key facts

- **NIH application ID:** 10237227
- **Project number:** 5R35CA220481-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Boris C. Bastian
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $951,000
- **Award type:** 5
- **Project period:** 2017-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237227

## Citation

> US National Institutes of Health, RePORTER application 10237227, Molecular and immunologic evolution of melanomas from pre-neoplastic lesions (5R35CA220481-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10237227. Licensed CC0.

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