A Collaborative Model for Accelerating the Discovery and Translation of Cancer Therapies

Abstract

Preclinical studies using genetically engineered mouse models (GEMMs) have the potential to expedite the development of effective new therapies; however, they are not routinely integrated into drug development pipelines. GEMMs may be particularly valuable for investigating treatments for less common cancers, which frequently lack alternative faithful models. Here we describe a multi-center cooperative group that has successfully leveraged the expertise and resources from philanthropic foundations, academia, and industry to advance therapeutic discovery and translation using GEMMs as a preclinical platform. This effort, known as the Neurofibromatosis Preclinical Consortium (NFPC), was established to accelerate new treatments for tumors associated with neurofibromatosis type 1 (NF1). At its inception, there were no effective treatments for NF1 and few promising approaches on the horizon. Since 2008 participating labs have conducted 95 preclinical trials of 38 drugs or combinations through collaborations with 18 pharmaceutical companies. Importantly, these studies have identified 13 therapeutic targets, which have inspired 16 clinical trials. This review outlines the opportunities and challenges of building this type of consortium and highlights how it can accelerate clinical translation. We believe that this strategy of foundation-academic-industry partnering is generally applicable to many diseases and has the potential to markedly improve the success of therapeutic development.

Molecular determinants of post-mastectomy breast cancer recurrence

“…We classified NF1 mutations as a MAPK alteration, consistent with recent breast cancer literature, and because of the greater interest in targeting NF1 germline-mutant tumors with MAPK targeting NF1 . 27 , 28 MAPK pathway is involved in many cellular processes including cell proliferation, differentiation, and transcriptional regulation. Studies evaluating MAPK genomic alterations in breast cancer are few in number; however, activation of MAPK signaling can confer resistance to therapy resulting in poorer outcomes, and MAPK pathway activation may promote immune evasion.…”

A Comprehensive Review on Schisandrin B and Its Biological Properties

“…Chemotherapies remain one of the most used methods for cancer treatment. These drugs inhibited cancer cell growth, therefore stopping the proliferation of cancer [30,31]. The cytotoxicity of Sch B was reported against a wide variety of human cancer cell lines (Table 1) with low concentration.…”

Delivering on the Vision of Bench to Bedside: A Rare Disease Funding Community Collaboration to Develop Effective Therapies for Neurofibromatosis Type 1 Tumors

“…The CTF's Neurofibromatosis Preclinical Consortium (NFPC, funded from 2008-2013) awarded almost $3.4 million for preclinical studies, followed by the Neurofibromatosis Therapeutic Consortium (NFTC, funded conjointly with NTAP from 2013-2016) that continued funding for $3.6 million. During the 2008-2013 period, the two consortia conducted more than 95 preclinical studies of 38 drugs or drug combinations through collaborations with 18 pharmaceutical companies (Maertens, et al 2017). Over 40 studies included a MEK inhibitor either as a single agent or in combination (unpublished results).…”