Publications by authors named "Joana L Mora"
Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently an end stage of the disease. Immune checkpoint inhibitors (ICI) provide a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique elements of the MBM TME and correlates of MBM response to ICI, we collected 32 fresh MBM and performed single-cell RNA sequencing of the MBM TME and T-cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions.
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- Leptomeningeal disease (LMD) is a serious complication in solid tumors, showing a poor prognosis and limited treatment options.
- A Phase II study involving 18 patients tested the combined treatment of ipilimumab and nivolumab, with promising results: 44% of patients were alive at three months, surpassing the expected 18%.
- While some patients experienced severe side effects, the overall safety profile was acceptable, indicating the need for larger studies to further assess the treatment's effectiveness.
Article Synopsis
- * We conducted two clinical trials to study the effectiveness of immune checkpoint inhibitors (ICI) in treating LMD and analyzed patient samples using advanced techniques like single-cell RNA sequencing.
- * Our research reveals important insights into the tumor environment in LMD and demonstrates the potential of using genomic profiling to enhance understanding and treatment strategies for this condition.
Article Synopsis
- Leptomeningeal disease (LMD) is a severe cancer complication often missed due to the low accuracy of current diagnostic methods like CSF cytology.
- This study aimed to evaluate if analyzing cell-free DNA (cfDNA) in CSF could provide a more reliable diagnosis for LMD compared to traditional cytologic methods.
- In a cohort of 30 patients, cfDNA analysis identified LMD correctly in 94% of follow-up samples, significantly outperforming cytologic analysis, indicating a potential improvement in diagnosing LMD.
Basal-like breast cancer (BLBC) shows brain metastatic (BM) capability and overexpresses EGFR and death-receptors 4/5 (DR4/5); however, the anatomical location of BM prohibits efficient drug-delivery to these targetable markers. In this study, we developed BLBC-BM mouse models featuring different patterns of BMs and explored the versatility of estem cell (SC)-mediated bi-functional EGFR and DR4/5-targeted treatment in these models. Most BLBC lines demonstrated a high sensitivity to EGFR and DR4/5 bi-targeting therapeutic protein, EDR [anti-EGFR VHH (E) fused to DR ligand (DR)].
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Article Synopsis
- An increasing number of metastatic cancer patients suffer from leptomeningeal dissemination (LMD), leading to poor survival rates; researchers conducted a phase 2 study of pembrolizumab to assess its effectiveness in these patients.
- The study included 20 patients with solid tumors (mostly breast cancer), who received pembrolizumab every 3 weeks, and the main goal was to evaluate overall survival at 3 months.
- The results showed that 60% of patients were alive at 3 months, with some side effects reported, suggesting pembrolizumab is safe and potentially beneficial for LMD, though more research is needed to pinpoint which patients may benefit the most.
Background: Activating mutations in the pathway of phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) occur in 43-70% of breast cancer brain metastasis patients. To date, the treatment of these patients presents an ongoing challenge, mainly because of the lack of targeted agents that are able to sufficiently penetrate the blood-brain barrier. GDC-0068 is a pan-Akt inhibitor that has shown to be effective in various preclinical tumor models as well as in clinical trials.
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