# Targeted Therapies for HIV-Associated Kaposi Sarcoma and Lymphoma

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $342,759

## Abstract

Abstract
 People infected with HIV can expect a near normal life on antiretroviral therapy. In the United States,
cancer has become the leading cause of death in the aging HIV-positive population. This includes the AIDS-
defining cancers Kaposi sarcoma (KS) and lymphomas, such as primary effusion lymphoma (PEL). In fact,
KS is the leading cause of death in the HIV-positive population today. Furthermore, as the HIV-positive
cohort ages they are at an increasing risk of developing KS, which is age dependent even in HIV-negative
KSHV-carriers.
 We, and others, have shown that KS and AIDS-associated lymphomas are highly dependent on the
PI3K/Akt/mTOR signaling pathway for survival. The mammalian target of rapamycin (mTOR) is a
serine/threonine kinase that is a downstream target of the PI3K and Akt kinases. Rapamycin is an allosteric
inhibitor of the mTORC1 complex and we conducted the first clinical trial of rapamycin in the context of HIV
infection. We showed that rapamycin was efficacious in mouse models of KS and PEL and that rapamycin
exhibited a direct anti-tumor effect independent of immune modulation.
 In this application, we propose to investigate additional targets in the PI3K/Akt/mTOR pathway in KSHV
cancers, as a model of HIV-associated cancers that are critically dependent on this pathway for their
survival. We propose to identify efficacious drug combinations and to delineate the molecular mechanism of
different therapeutic targets. This will uncover the next generation of therapies against KS and lymphoma in
the context of HIV infection. Since PI3K/Akt kinases have also been shown to be required for optimal HIV
infection and replication, we will also test these therapies against HIV replication. Importantly, we will mostly
evaluate drugs that have passed human phase I safety trials and thus will be immediately available for
clinical trials for HIV-associated KS and lymphomas.

## Key facts

- **NIH application ID:** 9978721
- **Project number:** 5R01CA163217-10
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** BLOSSOM A DAMANIA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $342,759
- **Award type:** 5
- **Project period:** 2011-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978721

## Citation

> US National Institutes of Health, RePORTER application 9978721, Targeted Therapies for HIV-Associated Kaposi Sarcoma and Lymphoma (5R01CA163217-10). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9978721. Licensed CC0.

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