PIK3CA

Genomic testing in cervical cancer enables personalized treatment by identifying genetic mutations, selecting targeted therapies, predicting drug resistance, optimizing immunotherapy, and improving prognostic predictions. This precision medicine approach enhances treatment outcomes, offering more effective therapies with fewer side effects, leading to better survival rates and quality of life.

AstraZeneca's Truqap (capivasertib) showed improved rPFS in PTEN-deficient mHSPC in the CAPItello-281 study, marking a recovery from earlier setbacks. Despite a restricted label and a TNBC trial failure, Truqap's potential in prostate cancer and its $125M Q3 sales highlight its significance. AZ plans to seek label expansion based on these findings.

L-NMMA combined with taxane shows clinical activity in MpBC patients, targeting NOS signaling. The combination therapy resulted in a 46% clinical benefit rate and 23% overall response rate, with manageable toxicity. NOS inhibition, alongside PI3K inhibition, enhances tumor response and reverses EMT in MpBC, suggesting a promising therapeutic strategy.

Allosteric inhibitors like STX-478 and RLY-2608 show promise in targeting PIK3CA mutations in breast cancer, offering better safety and efficacy by selectively inhibiting mutant PI3Kα, reducing toxicities seen with orthosteric inhibitors.

Alpelisib plus fulvestrant showed activity in PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced breast cancer after CDK4/6 inhibitor progression, with 6-month progression-free survival at 53.8% and manageable toxicity.

A multi-institutional team developed a computational methodology using biomarkers from the MMRF dataset and FDA database to identify optimal treatment regimens for multiple myeloma patients, reducing AEs and mortality. The study, presented at ASCO, used 7 machine learning algorithms to assess disease outcomes, identifying 11 genes significantly correlated with survival, and suggested AI's potential in optimizing clinical trials.

Genesis Therapeutics, founded in 2019 by Evan Feinberg, PhD, leverages AI for drug discovery, notably through its GEMS platform. With over $300M raised, including a $200M Series B, and collaborations with Nvidia and biopharma giants like Gilead, Eli Lilly, and Genentech, Genesis focuses on oncology and immunology, aiming to drug challenging targets with advanced AI and neural network technologies.

The 2024 San Antonio Breast Cancer Symposium highlighted advances in breast cancer research, including insights into tumorigenesis, CDK4/6 inhibitor resistance, and the role of AI in translational research. Key findings included the potential of p53 loss as a biomarker, improvements in liquid biopsy technologies, and the impact of immunotherapy in early-stage disease. The symposium also discussed new treatment strategies for metastatic breast cancer, emphasizing the importance of biomarker testing and the integration of CDK4/6 inhibitors with endocrine therapy.

Real-world outcomes for elacestrant in ESR1-mutant HR+/HER2- advanced breast cancer showed comparable or better time to treatment discontinuation and next treatment vs EMERALD trial PFS. Patients with PI3K pathway alterations had worse outcomes. Elacestrant efficacy remained consistent beyond second-line treatment, highlighting the need for precision medicine and combination treatments.

Orserdu showed similar or slightly higher time to treatment discontinuation and next treatment in HR-positive, HER2-negative advanced breast cancer with ESR1 mutation compared to EMERALD trial PFS. Real-world median time to next treatment was 6.43 months and to discontinuation was 4.6 months. Patients with PI3K pathway alterations had worse outcomes.