Journal
CLINICAL CANCER RESEARCH
Volume 27, Issue 5, Pages 1516-1525Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-20-2984
Keywords
-
Categories
Funding
- Melanoma Research Alliance
- Bloomberg-Kimmel Institute for Cancer Immunotherapy
- Barney Family Foundation
- Moving for Melanoma of Delaware
- Laverna Hahn Charitable Trust
- NCI [R01 CA142779]
- MSKCC [T32 CA160001-06, K99CA229979]
- NIH [P30 CA006973, R01CA205426, R35CA232097]
- Sol Goldman Pancreatic Research Center
- NIH/NCI Cancer Center [P30 CA008748]
- Pershing Square Sohn Cancer Research grant
- PaineWebber Chair
- STARR Cancer Consortium
Ask authors/readers for more resources
This study used whole-exome sequencing of 110 melanoma tumors from 7 patients and analyzed the genetic diversity among tumors to explore treatment resistance mechanisms. Results showed that multiple acquired and intrinsic resistance mechanisms coexisted in the same patient, suggesting that future therapies targeting these mechanisms may be broadly effective, especially in immunotherapy.
Purpose: Melanoma is a biologically heterogeneous disease composed of distinct clinicopathologic subtypes that frequently resist treatment. To explore the evolution of treatment resistance and metastasis, we used a combination of temporal and multi-lesional tumor sampling in conjunction with whole-exome sequencing of 110 tumors collected from 7 patients with cutaneous (n = 3), uveal (n = 2), and acral (n = 2) melanoma subtypes. Experimental Design: Primary tumors, metastases collected longitudinally, and autopsy tissues were interrogated. All but 1 patient died because of melanoma progression. Results: For each patient, we generated phylogenies and quantified the extent of genetic diversity among tumors, specifically among putative somatic alterations affecting therapeutic resistance. Conclusions: In 4 patients who received immunotherapy, we found 1-3 putative acquired and intrinsic resistance mechanisms coexisting in the same patient, including mechanisms that were shared by all tumors within each patient, suggesting that future therapies directed at overcoming intrinsic resistance mechanisms may be broadly effective.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available