Request for Proposal: PIK3CA-Related Overgrowth Spectrum (PROS)
Novartis Oncology Office of Grants & Education Professional Medical Education
The Novartis Oncology Office of Grants & Education (OGE) supports independent high-quality medical educational programs which provide fair-balanced, evidence-based, current scientific information to healthcare professionals in order to positively improve patient care. Activities should have an educational focus, be independent of commercial bias and be non-promotional in nature. OGE will perform these duties in compliance with laws, regulations and guidelines as established by the ACCME, PhRMA Code, OIG, other regulatory agencies and in compliance with Novartis guidelines and policies.
PIK3CA-Related Overgrowth Spectrum (PROS)
RFP Issued: July 30, 2021 Applications Due to Novartis: September 30, 2021 by 5 PM EST Notification of Grant Decisions: October/November 2021 Educational Programming Starts: Q4-2021 – Q1 2022
Tissue proliferation is a tightly regulated process in the organism from embryonic development to adult life. One of the main regulators of cell proliferation is the PI3K/AKT/mTOR signaling pathway, which is a well-known target of multiple therapeutic strategies. The hyper-activation of the PI3K/AKT/mTOR pathway results in significant dysregulation of cellular functions, which in turn leads to a competitive growth advantage. Somatic mutations and gains or losses in these genes are linked to many different solid and hematological tumors (De Santis et al 2017).
In addition to the well-characterized role of PIK3CA in cancer, post zygotic somatic mutations in PIK3CA have also been identified in a spectrum of overgrowth disorders comprising a wide group of clinically recognizable mutation-driven malformations referred to as PIK3CA-related overgrowth spectrum (PROS) (De Santis et al 2017).
PIK3CA-Related Overgrowth Spectrum (PROS) designates a heterogeneous group of rare, asymmetric overgrowth disorders caused by post zygotic variants in the gene PIK3CA (Keppler-Noreuil et al 2014). PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), which transduces activation of tyrosine kinase growth factor and hormone receptors into activation of Protein Kinase B (AKT) and Mammalian Target of Rapamycin (mTOR) signaling to promote tissue growth. In PROS, activation of this pathway is associated with overgrowth which may include adipose tissue, muscle, skin, bone, blood or lymph vessels, or neural tissue (Kurek et al 2012, Lindhurst et al 2012). The prevalence of PROS is difficult to estimate because of its rarity, its recent characterization (i.e., in 2014 by the National Institutes of Health), variation in ascertainment, the broad phenotypic spectrum, and the occurrence of atypical or mild phenotypes leading to misdiagnosis (Keppler-Noreuil et al 2014, Mirzaa et al 2013). The incidence rate was estimated by medical experts to be approximately 1 in 70,000; essentially based on the number of patients they see. PROS is characterized by congenital or early childhood-onset overgrowth, sporadic occurrence, and mosaic distribution. Segmental overgrowth is often congenital at onset, but it is usually noted by 1 year of age with progressive overgrowth of tissues persisting in some cases into adulthood. Though some genotype–phenotype correlation in PROS has been suggested (Mirzaa et al 2016, Keppler-Noreuil et al 2014), the main determinant of phenotype is the timing and location of the pathogenic mutation. Consequently, PROS is characterized by a high degree of interindividual phenotypic heterogeneity. The overgrowth features vary greatly for reasons which are unknown: some lesions exhibit excess growth which is limited to childhood, while other individuals have progressive soft tissue overgrowth during adult life. Complications of PROS depend on the anatomical site and extent of overgrowth, but may include functional impairment (e.g., of walking or swallowing), pain, cardiac function impairment, pulmonary hypertension, seizures, impaired neurological development, recurrent superficial infections, thromboembolism, and/or hemorrhage, amongst other manifestations all of which may be debilitating, and cause early mortality. Current treatment relies on surgery primarily with debulking objectives - amputation, and/or endovascular occlusive procedures. Regrowth following surgery frequently occurs and often requires repeated surgery. There is large unmet need for targeted, new therapeutic approaches and effective treatments to combat PROS.
Disorders that lead to inappropriate activation of the PI3K/AKT/mTOR pathway have been shown to result in tissue overgrowth in association with vascular anomalies. Inhibitors targeting different components of the PI3K/AKT/mTOR signaling pathway are/were under clinical investigation (Keppler-Noreuil et al 2016, Suzuki et al 2017, Venot et al 2018). However only a very limited number of clinical studies were conducted with medical treatment in the PROS population.
OGE has identified the need for innovative continuing medical education programs that strive to optimize patient outcomes through education on:
The barriers to optimal care due to lack of awareness of PROS, PROS terminology and the various disorders that fall under within this umbrella term
The challenges in PROS diagnosis, including phenotypic variability of these disorders, the impact of diagnostic delay/disease burden, and/or challenges with genetic testing
Consideration of the patient’s perspective, quality of life and burden of disease when formulating a treatment plan for PROS
Recognition of treatment options for PROS and the importance of treating the underlying disease as well as the symptoms
The barriers to optimal care due to lack of awareness of PROS Guidelines
The role of a multi-disciplinary team and need for a collaborative approach in the diagnosis and treatment of PROS
OGE can consider support for innovative educational programs:
Virtual/Live programs with enduring component (stand-alone or in conjunction with PROS-related medical societies, congresses)
Virtual/Live series of programs, along with an enduring component.
Note: All aspects of the Program(s) including location and placement are independent of Novartis.
National, Regional, and/or Local
Healthcare providers who are involved in the care of patients with PROS, including but not limited to: Pediatricians, Primary Care Clinicians, Internal Medicine Physicians, Dermatologists, Neurologists, Hematologists/Oncologists, Maternal-Fetal Physicians, PAs, NPs
Educational providers should include the target number of participants. Further, please include details on proposed audience recruitment.
Please note: Novartis will not participate in the distribution of invitations to the CME/CE event.
Multiple single-support or multi-support initiatives may be funded; Up to $350,000 in total support is available.
If working with an Accredited Provider and/or Educational Partner, they should be listed in the Novartis grant application. Grant requests must be submitted by the Office of CME (if from an Academic Institution/Hospital) via the Online Portalby 5 PM EST on September 30, 2021 to be considered.
The grant application should include “RFP Response” within the Program Title [example: “RFP Response: Program Title”].
Proposals that include collaborations with third parties, including (but not limited to), medical societies, health education companies/centers, not-for-profit organizations, and academic institutions, are encouraged, as appropriate.