Mapping the Routes to Tumor Cell Death in TSC
Abstract
Individuals with tuberous sclerosis complex (TSC) are at risk of developing a variety of tumors, primarily affecting the brain,kidneys, skin, lung, heart, and eyes. Rapamycin/sirolimus and its analogs, such as everolimus, are effective at shrinking thevariety of tumors arising in TSC patients and appear to halt further tumor growth. However, these drugs do not eliminatetumors, and upon withdrawal of treatment, tumors regrow at a remarkably rapid rate. Thus, there is an unmet need fortreatments that elicit a more complete and durable response that allows TSC patients to avoid continuous therapy withrapalogs. This current study uses cutting edge new techniques to study the molecular nature of tumor cell death and survival inTSC and represents a comprehensive and novel strategy to tackle this problem. The study will identify and test, in multiplepreclinical tumor models, new therapeutic approaches to induce tumor cell death in TSC, thereby eliminating existing tumors.We will focus on an emerging and promising class of drugs, called BH3 mimetics, which are being developed and FDAapproved for use in cancer therapy. We anticipate that a subset of these drugs, when used in combination with rapamycin orits analogs, will safely induce cell death specifically in the tumors of TSC patients, thereby eradicating these lesions. Throughrigorous testing in multiple preclinical models, it is our hope that the completion of our study in the next three years will providethe preclinical evidence needed to advance these treatment strategies into the clinic to benefit TSC patients and offer animproved response to that currently achieved with rapamycin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2020
- Accession Number
- AD1115077
Entities
People
- Brendan D Manning
Organizations
- President and Fellows of Harvard College