The ERK1/2 and PI3K signaling pathways play important roles in cellular proliferation, survival, differentiation, and metabolism. In cancer, these pathways are frequently dysregulated and overactivated, resulting in poor patient prognosis and resistance to treatment. These pathways are activated by receptor tyrosine kinases and send downstream signals to effectors such as RAS, RAF, MEK, AKT, and mTOR. In this review, we highlight the key components of the ERK1/2 and PI3K pathways, the roles they play in tumor progression, and the development of inhibitors and combination therapies designed to enhance therapeutic outcomes and address treatment resistance. Our review demonstrates the need and promise for future research and clinical trials for inhibitors and combination therapies for the ERK1/2 and PI3K pathways in cancer.

Disease burden has been used to predict National Institutes of Health (NIH) funding but included diseases with little underlying relationship. Here we focus on cancers to create a more appropriate model to allow for more targeted scrutinization of funding allocation. An ecological study using NIH funding data (2008–2023) was performed. Inclusion of cancers was based on their presence in the NIH Research Portfolio Online Reporting Tool and the 2021 Global Burden of Disease (GBD) study. Disability-adjusted life years (DALY) were collected and to evaluate the impact of public interest, Google Trends data was used. Multivariable linear regression determined appropriate funding based on disease burden and public interest. To quantify how each cancer’s funding differed from model predictions residual values were used to calculate the percent over/under funding. Fifteen cancers met inclusion criteria. Neuroblastoma had the greatest ratio of funding to DALYs per 100,000 people (US$14,000,000) while lung cancer had the lowest (US$300,000). Stomach cancer was the most underfunded (197.9% [95% CI: 136.0%, 276.2%]) while brain cancer was the most overfunded (64.1% [95% CI: 53.8%, 72.1%]). Even at their lowest funding values in the study period brain, breast, and colorectal cancer all had greater than 40% overfunding. Contrarily, the lowest annual funding for leukemia, uterine, and stomach cancer received less than 150% of expected funding. Despite its overfunding brain cancer had an increase in DALYs in the study period. Modeling by disease category demonstrated disparities in funding indicating the need for reevaluation for possible funding inequities. The year-by-year approach taken in this study will drive the ability for future research to better understand NIH funding decisions. Additionally, the role of public interest in research funding needs to be further evaluated to ensure that popularity does not override disease burden, in funding decisions. No Funding.

Objective The 2024 Residency Match was the first in recent history where most applicants did not report a numerical United States Medical Licensing Examination Step 1 score. This study will quantify the effects the scoring change had on the research productivity of successfully matched neurosurgery applicants. Methods Data on sex, MD/PhD status, medical school attended, and residency program were collected. Articles were categorized based on authorship, relation to neurosurgery, type of article, and the h5-index of the journal. Differences were evaluated based on sex, top 40 National Institutes of Health-funded medical school status, and acceptance at a top 30 residency program. Results This study evaluated the publications of 181 out of 241 matched students. They produced 2,002 articles, 85% of which were related to neurosurgery. Clinical studies were the most frequently published. The mean and median total publications were 11.1±12.8 and 8.0, respectively. On average, first-author publications accounted for 2.9±4.0 (median=2.0) of publications. Significant differences in publication metrics were found when comparing based on sex and matching into a top 30 residency program. Conclusions The transition of the Step 1 scoring system to Pass/Fail amplified the emphasis successful applicants placed on research. The need for an extensive research portfolio has only become greater. Results of this study may also suggest that the change to Step 1 scoring may not have lessened the burden on medical students but rather shifted it elsewhere.