- |||||||||| everolimus / Generic mfg., fulvestrant / Generic mfg., capecitabine / Generic mfg.
Treatment Patterns Following First Line CDK4/6 Inhibitor Progression in HR+, HER2- Metastatic Breast Cancer () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_397;
Although treatment patterns after progression on a first line CDK4/6i vary, suggesting no standard of care for subsequent treatment, chemotherapy was the most common therapy after progression. Prognosis after second- line treatment remains a challenge, and more research and effective treatments options for patients with HR+ HER2- MBC are needed to delay time to chemotherapy.
- |||||||||| everolimus / Generic mfg.
Transposable element expression patterns in epigenetic mutational subtypes of clear cell renal cell carcinoma (Section 16) - Mar 5, 2024 - Abstract #AACR2024AACR_8440;
Coupled with PBRM1 inactivation, their expression served as a candidate biomarker of improved PFS in IO-treated ccRCC that may have additional biological relevance. Expanded functional and clinicogenomic studies of epigenetic mutational subtype-specific patterns of TE expression, and their relation to selective IO response, may guide additional discovery and therapeutic development strategies in ccRCC.
- |||||||||| Sutent (sunitinib) / Pfizer
DUSP6 is a novel target in neuroendocrine tumors (Section 27) - Mar 5, 2024 - Abstract #AACR2024AACR_7951;
BCI treatment induced an apoptotic response in the NET models and synergistically increased sensitivity to TMZ and cisplatin in 1452 cells., RNAi-mediated depletion of DUSP6 also increased sensitivity to sunitinib and triggered TMZ-induced apoptotic cell death in 1452 cells, which was associated with changes in (O6-Methylguanine-DNA-methyltransferase) MGMT expression. These findings suggest that DUSP6 is an important therapeutic target in neuroendocrine tumors and its blockade is a promising therapeutic approach to enhance the therapeutic index of current treatments.
- |||||||||| DT2216 / Dialectic Therap, MRTX1133 / BMS
Rational targeting of BCL-xL and/or mTOR enhance the efficacy of KRASG12D inhibitor in pancreatic cancer (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_6724;
Our findings suggest SMARCD3 upregulation promotes resistance to everolimus treatment and may serve as a novel therapeutic target in ER+ breast cancer. Our findings suggest that the single agent efficacy of MRTX1133 is limited due to apoptosis inhibition and complimentary senescence induction, and therefore its combination with DT2216 and/or everolimus is synergistic, which can potentially overcome resistance, by enhanced apoptosis and clearance of senescent cells.
- |||||||||| voxtalisib (SAR245409) / Sanofi, ipatasertib (RG7440) / Roche, Torin1 / InvivoGen
Cancer associated fibroblast dependency in a model of bladder cancer (Section 6) - Mar 5, 2024 - Abstract #AACR2024AACR_4624;
The use of next-generation mTORC1 inhibitors can overcome resistance in some cases, providing a rationale for their implementation in the treatment of patients with MBC. These organoids were co-edited for Trp53 and Rb1 KO, and further editing of the Pten gene resulted in a nine-fold increase in sensitivity to the kinase inhibitor ipatasertib...While TSC1/TSC2 KO lines exhibited elevated P-S6K signaling, they displayed resistance to Torin 1, Voxtalisib, and Everolimus
- |||||||||| everolimus / Generic mfg., erlotinib / Generic mfg.
Unraveling the oncogenic potential of KDM2A with gastric organoids (Section 16) - Mar 5, 2024 - Abstract #AACR2024AACR_4304;
In addition, KDM2A expression was significantly higher in GAC samples than in normal tissues, and high expression of KDM2A was associated with poor survival in GAC patients. To examine the effect of KDM2A knockdown on characteristics of GAC, we used gastric organoids generated from KDM2Aflox/flox mouse stomach.
- |||||||||| EGFR and mTOR signaling facilitate RET-independent resistance to selective RET-TKIs (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_4117;
To determine whether EGFR or MET signaling facilitate RET inhibitor resistance, LC-2/ad and NCCE-TH1101 (KIF5B-RET) NSCLC cells were treated with increasing concentrations of selpercatinib or pralsetinib with or without ligands for these receptors, EGF or HGF respectively, and after five days cell viability was measured by CellTiter Glo...Next, to evaluate whether blockade of EGFR or MET signaling could enhance the activity of RET inhibitors, we treated LC-2/ad and NCCE-TH1101 cells with RET TKIs alone or in combination with the EGFR TKI erlotinib or poziotinib, or the MET inhibitor SU11274...We observed that treatment of LC-2/ad and NCCE-TH1101 cells with an mTOR inhibitor (everolimus) or a MEK inhibitor (trametinib) in combination with RET TKIs increased the anti-tumor activity or RET inhibitors...RET TKI resistant cells were sensitive to mTOR or MEK inhibitors in combination with RET TKIs. Collectively, our findings indicate that in RET-fusion positive NSCLC tumor cells, activation of bypass pathways including the EGFR, MAPK, mTOR pathways may facilitate RET inhibitor resistance and that blockade of bypass pathways may enhance the efficacy of selective RET inhibitors and overcome acquired RET TKI resistance.
- |||||||||| Lumakras (sotorasib) / Amgen
Acquired resistance to sotorasib in KRASG12C mutant NSCLC is vulnerable to PI3K-mTOR pathway inhibition and regulated by 4E-BP1 (Section 24) - Mar 5, 2024 - Abstract #AACR2024AACR_4015;
Both resistant PDXOs and cell lines showed resistance to adagrasib, another selective, KRASG12C inhibitor...Inhibition of PI3K, AKT and mTOR by copanlisib, MK2206 and everolimus respectively was synergistic with sotorasib in AR cells and PDXOs, with copanlisib being the most effective...When copanlisib was combined with sotorasib in treating the resistant TC303AR, TC314AR PDXs, H358AR CDX and H23AR xenograft tumors, antitumor effects were observed in every model. Inhibition of the PI3K pathway at different nodes is a vulnerability in KRASG12C mutant NSCLC with sotorasib AR and p4E-BP1 is a mediator of sotorasib resistance
- |||||||||| camizestrant (AZD9833) / AstraZeneca
Enrollment closed, Metastases: SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - Mar 5, 2024
P1, N=396, Active, not recruiting,
These findings describe a novel mechanism of transendothelial fatty acid transportation during metastatic outgrowth, supporting future development of therapeutic strategies to target endothelial mTORC1 activity. Recruiting --> Active, not recruiting
- |||||||||| MK-2206 / Merck (MSD), Zydelig (idelalisib) / Gilead
Preclinical, Journal: Glucose Metabolism in Acute Myeloid Leukemia Cell Line Is Regulated via Combinational PI3K/AKT/mTOR Pathway Inhibitors. (Pubmed Central) - Mar 4, 2024
A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells. Combinational therapy approaches to block these pathways might be a promising and novel therapeutic strategy for targeting the metabolic requirements of AML cells.
- |||||||||| everolimus / Generic mfg.
Journal: Pulmonary Complications of Everolimus in Liver Transplant Patients: A 10-Year Experience. (Pubmed Central) - Mar 4, 2024
Overall, 51.3% of patients who received everolimus during their post-transplant course discontinued the medication (n=80). Everolimus is safe from a pulmonary toxicity standpoint in liver transplant immunosuppression regimens as there was no significant difference found in pulmonary complications between patients who received the medication and those who did not.
- |||||||||| everolimus / Generic mfg.
Journal: FOXO3a Induces Myocardial Fibrosis by Upregulating Mitophagy. (Pubmed Central) - Mar 4, 2024
The adaptive immune system and PIK3R1 may be involved in DCM disease progression, while ERBB2 exerts a protective effect against DCM. FOXO3a promotes the progress of myocardial fibrosis by triggering mitophagy in cardiac fibroblasts.
- |||||||||| Lutathera (lutetium Lu 177 dotatate) / Novartis, Sandostatin LAR Depot (octreotide acetate) / Novartis
Journal: Sequencing of Somatostatin-Receptor-Based Therapies in Neuroendocrine Tumor Patients. (Pubmed Central) - Mar 4, 2024
This question is particularly complicated given the heterogeneity of NETs and the near absence of randomized trials comparing active treatment options. This state-of-the-art review examines the evidence supporting use of somatostatin-receptor-targeted treatments within the larger landscape of NET therapy and offers insights regarding optimal patient selection, assessment of benefit versus risk, and treatment sequencing.
- |||||||||| everolimus / Generic mfg., furosemide / Generic mfg.
SGLT2i use in heart trasplant patients with persistent congestion. A real experience report (Moderated ePosters 2) - Mar 4, 2024 - Abstract #HEARTFAILURE2024HEART_FAILURE_1549;
In our study, adequate tolerance to SGLT2i treatment was observed in transplant patients with refractory HF symptoms to conventional diuretic treatment. iSGLT2 treatment may be an option to consider in heart trasplant patients with persistent congestive symptoms despite standard diuretic regimen.
- |||||||||| Toll-like receptor-mediated inflammatory disease therapy / Pfizer, Opsona, Saphnelo (anifrolumab) / AstraZeneca, Tavalisse (fostamatinib) / Rigel
B cell, T cell, cytotoxic/NK cell, and mitochondrial gene dysregulation patterns separate neuropsychiatric systemic lupus erythematosus patients into two distinct subgroups with differential anticipated response to targeted therapies (Concert Hall) - Feb 25, 2024 - Abstract #LUPUS2024LUPUS_50;
Conclusion In this cohort of SLE patients of European origin, B cell, T cell, cytotoxic/NK cell, and mitochondrial gene dysregulation patterns separated active CNS lupus patients into two distinct subgroups with differential anticipated response to type I interferon and calcineurin inhibition. Our study provides a conceptual framework for precision medicine in CNS lupus.
- |||||||||| itacitinib (INCB039110) / Incyte
Trial completion date, Combination therapy: Itacitinib + Everolimus in Hodgkin Lymphoma (clinicaltrials.gov) - Feb 21, 2024
P1/2, N=23, Active, not recruiting,
The most promising compounds 12b and 12d exhibited excellent antitumor activity against the leukemia SR cell line, which is the most sensitive cell line, with IC50 0.10 Trial completion date: Jan 2027 --> Jun 2027
- |||||||||| Piqray (alpelisib) / Novartis
Journal, Tumor cell: Concomitant inhibition of PI3K/mTOR signaling pathways boosts antiproliferative effects of lanreotide in bronchopulmonary neuroendocrine tumor cells. (Pubmed Central) - Feb 20, 2024
We focused on assessing whether pretreating cells with inhibitors for phosphatidylinositol 3-kinase (PI3K) and mammalian target for rapamycin (mTOR) could enhance the antiproliferative effects of lanreotide...Additionally, combination treatment consisting of BYL719 and everolimus plus lanreotide tested in NCI-H720 and NCI-H727 led to diminished cell proliferation in a dose-dependent manner...Interestingly, SSTR expression reinduction could be exploited in therapeutic and diagnostic applications. The overall results of this study support the evaluation of combination-based therapies using lanreotide in preclinical studies to further increase its antiproliferative effect and ultimately facilitate its use in high-grade tumors.
- |||||||||| prednisone / Generic mfg., everolimus / Generic mfg.
Chronic Cough in an Immunosuppressed Patient: A Challenging Asthma Case. A Case Report (San Diego Convention Center, Area H (Hall H, Ground Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_6747;
Currently, grouping patients based on common characteristics and pathophysiological mechanisms is a challenge, and at times, the differentiation can be imprecise due to overlap. The current course of the condition was considered partially controlled severe asthma, characterized as difficult to treat due to comorbidities.
- |||||||||| temozolomide / Generic mfg., everolimus / Generic mfg., amoxicillin / Generic mfg.
A Case Report of a Bronchial Carcinoid Tumor in an Adolescent Female Presenting as Recurrent Pneumonia (San Diego Convention Center, Area A (Hall A-B2, Ground Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_6491;
In patients with multiple primaries, metastatic spread, and recurrence, treatment options include targeted therapy with everolimus (FDA-approved for the treatment of unresectable bronchial carcinoid in adults), cytotoxic chemotherapy (such as temozolomide-based regimens), somatostatin analogs and peptide receptor radionucleotide therapy . 4
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Pulmonary Considerations in Patients With Advanced Cystic Fibrosis in the Setting of Acute Liver Transplant Rejection (San Diego Convention Center, Area G (Hall A-B2, Ground Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_4042;
Introduction: We present cases of pulmonary considerations of patients with cystic fibrosis (CF) and liver transplantation that discontinued elexacaftor/tezacaftor/ivacaftor (ETI) in the setting of acutely increased transaminases...She was treated with inhaled tranexamic acid and required bronchoscopy with saline lavage, forceps and cryotherapy to remove extensive blood clots...Everolimus and Carfilzomib have increased risks for interstitial lung disease, while Carfilzomib increases risk of pulmonary hypertension and sensations of dyspnea...It is imperative for re-initiation and dosing for ETI once liver injury has resolved. Optimizing the overall health of CF patients requires balance between multisystem complications even in the age of highly effective modulators.
- |||||||||| everolimus / Generic mfg.
Sirolimus Safely Used in a Patient After Everolimus-induced Pneumonitis: A Case Report (San Diego Convention Center, Area A (Hall A-B2, Ground Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_1572;
Sirolimus could be initiated with a smaller dose and follow-up closely in adverse effects, drug concentration and efficacy. Although both sirolimus and everolimus exert therapeutic effects by inhibiting mTOR, the mechanisms in causing interstitial pneumonitis are probably different and need to be further explored.
- |||||||||| PRT2527 / Prelude Therap, PRT1419 / Prelude Therap, Sutent (sunitinib) / Pfizer
Journal, IO biomarker: PBRM1 loss is associated with increased sensitivity to MCL1 and CDK9 inhibition in clear cell renal cancer. (Pubmed Central) - Feb 19, 2024
PRT2527, a potent CDK9 inhibitor which depletes MCL1, was similarly efficacious in monotherapy and in combination with Sunitinib in PBRM1-loss cells. Taken together, these findings suggest PBRM1 loss is associated with MCL1i sensitivity in ccRCC and provide rationale for the evaluation of PRT1419 and PRT2527 for the treatment for PBRM1-deficient ccRCC.
|
