# Investigation of 9-cis Retinoic Acid as a Novel Treatment for Post-Surgical Lymphedema

> **NIH NIH K08** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $25,651

## Abstract

Project Summary/Abstract
Lymphedema is an incurable condition characterized by tissue swelling after lymphatic damage. It affects over
140 million individuals worldwide and is associated with poor quality of life due to extremity disability,
disfigurement, and risk for recurrent limb-threatening infection. In the US, lymphedema is usually due to lymph
node resection in association with the treatment of malignancies such as breast or pelvic tumors. There are
currently no known medical therapies that can prevent or reverse the clinical progression of lymphedema in
humans. However, recent data suggests that surgical transfer of vascularized lymph nodes (VLN) to replace
damaged lymph nodes or divert lymphatic flow from a distal extremity may limit and even reverse disease
progression. Since lymphatic damage and backflow is the root cause of lymphedema, we hypothesize that
exogenous stimulation of lymphangiogenesis at the time of the initiating lymphatic injury may be an effective
strategy to prevent and/or treat lymphedema. We have previously demonstrated that 9-cis retinoic acid (9-cis
RA) can promote lymphangiogenesis in vitro and can limit lymphedema in vivo. The specific aims of this
proposal are: 1) To elucidate the mechanism by which 9-cis RA acts to minimize surgically induced
lymphedema in vivo; 2) To determine the minimal effective dose (MED) of 9-cis RA necessary to prevent post-
surgical lymphedema; and 3) To determine effect of 9-cis RA on vascularized lymph node flap transfers (VLN)
using a novel transgenic fluorescent lymphatic reporter rat. We expect data from these studies to support
rapid translation to human clinical trials, especially since 9-cis RA (Alitretinoin) is already FDA approved. Data
from this proposal has the potential to re-purpose 9-cis RA as the first pharmacologic agent used to
significantly impact the onset and progression of secondary lymphedema. Dr. Alex Wong, the principal
investigator of this grant, is a surgeon-scientist who has a long-term goal of becoming an independent
investigator in the field of lymphedema. He goal is to become an expert in RA therapy for lymphedema and
lead clinical trials using RA and other modalities. Dr. Young-Kwon Hong, PhD is the primary mentor for this
grant, is an international expert in lymphagiogenesis and lymphedema. He is an established investigator with
NIH R-series funding and has a solid track record in mentoring PhD and MD scientists to independence. The
proposed career development plan that integrates scientific investigation, formal course work, and frequent
meetings to assess scientific progression will be essential for Dr. Wong's goals towards independence.

## Key facts

- **NIH application ID:** 10438477
- **Project number:** 7K08HL132110-05
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Alex K. Wong
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $25,651
- **Award type:** 7
- **Project period:** 2017-02-01 → 2022-06-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438477

## Citation

> US National Institutes of Health, RePORTER application 10438477, Investigation of 9-cis Retinoic Acid as a Novel Treatment for Post-Surgical Lymphedema (7K08HL132110-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10438477. Licensed CC0.

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