- |||||||||| pelcitoclax (APG-1252) / Ascentage Pharma
Caspase-3 mediated cleavage of GSDME enhances the antitumor efficacy of HER2-targeted therapy in HER2-positive gastric cancer (Section 16; Poster Board #2) - Mar 14, 2023 - Abstract #AACR2023AACR_8378;
This work was suggesting that afatinib and lapatinib act as MAPK3 inhibitors and might be developed for leishmaniasis treatment. Taken together, our data indicated that anti-HER2 agents could upregulate the expression of GSDME, and the combination of lapatinib and APG-1252 showed a synergistic antitumor effect against HER2-positive gastric cancer through inducing caspase-3/GSDME mediated apoptosis and pyroptosis.
- |||||||||| Piqray (alpelisib) / Novartis, Sutent (sunitinib) / Pfizer
Oxygen tension - dependent differences in cancer cell kinome (Section 11; Poster Board #11) - Mar 14, 2023 - Abstract #AACR2023AACR_7497;
These findings suggest that ambient and physioxic oxygen tensions differentially impact cancer relevant signaling pathways. Therefore, it may be necessary to carry out preclinical cancer studies in the context of physiologically relevant oxygen tensions to aid translatability.
- |||||||||| Truxima (rituximab-abbs) / Teva, Mundipharma, Celltrion, Nippon Kayaku, Indukern, Servier, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
AI-driven image analysis enables simplified, label-free cytotoxicity screening (Section 33; Poster Board #1) - Mar 14, 2023 - Abstract #AACR2023AACR_6829;
In contrast, Lapatinib and Tamoxifen induced morphological change - but minimal cell death - in triple negative MDA-MB-231 cells...Cisplatin, doxorubicin, vinblastine and taxol induced concentration-dependent cell death in A172 and T98G cells; U87 cells displayed resistance to each of these compounds with a maximal 46.5% cell death induced by doxorubicin. Ramos B-cell lymphoma cells were exposed to increasing concentrations of monoclonal antibody Rituximab and the biosimilar Truxima
- |||||||||| Role of individual HER family members and pan-HER targeting treatment strategy in NRG1 fusion positive cancer (Section 21; Poster Board #16) - Mar 14, 2023 - Abstract #AACR2023AACR_6231;
Treatment with cetuximab, an antibody that targets EGFR, in combination with trastuzumab and pertuzumab yielded a synergistic effect on tumor cell killing. These data indicate that HER4 and EGFR can play a role in NRG1 fusion-driven signaling through crosstalk with HER2/HER3 and thus, pan-HER/EGFR inhibitors are more effective than EGFR/HER2 or HER2/HER4-selective inhibitors, highlighting the therapeutic potential of targeting multiple members of the HER family in NRG1 fusion driven cancers.
- |||||||||| TAS2940 / Otsuka
TAS2940 inhibits intracranial tumor growth and prolongs survival in HER2-aberrant and EGFR-amplified patient-derived xenograft models (Section 20; Poster Board #14) - Mar 14, 2023 - Abstract #AACR2023AACR_6207;
P1
Here, we demonstrate that TAS2940 induces downregulation of phosphorylated HER2/EGFR, reduces tumor burden, and promotes a significant increase in survival in intracranial xenograft mouse models with HER2-amplification (BC), HER2-Exon20 insertion mutation (NSCLC), and EGFR-amplification (GBM). These promising preclinical data highlight potential novel therapeutic strategies for patients with EGFR-aberrant GBM and brain metastases harboring HER2/EGFR alterations, and may help support the advancement of the ongoing first-in-human clinical trial (NCT04982926) for TAS2940 in solid tumors with EGFR and/or HER2 alterations.
- |||||||||| Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca, Gilotrif (afatinib) / Boehringer Ingelheim
Combination of T-DXd with the irreversible pan-HER TKI afatinib drives combination benefit in HER2-low gastric and lung tumors (Section 19; Poster Board #22) - Mar 14, 2023 - Abstract #AACR2023AACR_6073;
In HER2 low gastric and lung preclinical models, T-DXd combined with irreversible pan-HER inhibitor induced superior antitumor effects compared to single agents or the combination of T-DXd with reversible inhibitors. These data support the rationale to test combination of T-DXd and pan-HER irreversible inhibitors in the clinical setting.
- |||||||||| Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Metronomic gemcitabine plus neratinib effectively inhibits the growth of human Her-2 positive breast cancer cells intracranially implanted into immunodeficient mice (Section 19; Poster Board #21) - Mar 14, 2023 - Abstract #AACR2023AACR_6072;
These results point to intriguing effects of chemotherapy when used at continuous low (metronomic) doses, that in these studies involved gemcitabine administration every 3 days, and which in these models can be effectively combined with neratinib to suppress the growth of Her-2 positive breast cancer cells implanted into the mouse brain. These results highlight promising combination that could be used to suppress Her-2 positive breast cancer brain metastatic growth, and the developed models should facilitate the study of this subset of breast cancers.
- |||||||||| trastuzumab rezetecan (SHR-A1811) / Jiangsu Hengrui Pharma
Safety, tolerability, pharmacokinetics, and antitumor activity of SHR-A1811 in HER2-expressing/mutated advanced solid tumors: A global phase 1, multi-center, first-in-human study (Section 45; Poster Board #7) - Mar 14, 2023 - Abstract #AACR2023AACR_5998;
Subgroup analyses of ORRNo. of prior treatment lines in metastatic setting in all pts (N=250)HER2 positive BC (N=108)HER2-low BC (N=77)Other tumor types (N=65)?381.8% (45/55)58.7% (27/46)36.7% (18/49)>381.1% (43/53)51.6% (16/31)31.3% (5/16)Prior anti-HER2 therapies in pts with BC (N=185)*HER2 positive BC (N=108)HER2-low BC (N=77)All BC (N=185)Any82.2% (88/107, 73.7-89.0)68.8% (11/16, 41.3-89.0)80.5% (99/123, 72.4-87.1)Trastuzumab81.9% (86/105, 73.2-88.7)75.0% (9/12, 42.8-94.5)81.2% (95/117, 72.9-87.8)Pertuzumab83.0% (39/47, 69.2-92.4)100% (5/5, 47.8-100)84.6% (44/52, 71.9-93.1)Pyrotinib86.9% (53/61, 75.8-94.1)71.4% (5/7, 29.0-96.3)85.3% (58/68, 74.6-92.7)Lapatinib80.0% (28/35, 63.1-91.6)100% (1/1, 2.5-100)80.6% (29/36, 64.0-91.8)T-DM182.4% (14/17, 56.6-96.2)100% (3/3, 29.2-100)85.0% (17/20, 62.1-96.8)Other HER2-ADC (except T-DM1)**60.0% (9/15, 32.3-83.7)50.0% (2/4, 6.8-93.2)57.9% (11/19, 33.5-79.8)ORR in pts with tumor types other than BC (N=65)HER2 IHC3+ or IHC2+/ISH+ (N=36)HER2 IHC2+/ISH- or IHC1+ or unknown (N=29)All other tumor types (N=65)% (n/N)38.9% (14/36)31.0% (9/29)35.4% (23/65)ORR was shown as % (n/N, 95% CI) or % (n/N).
- |||||||||| Herceptin (trastuzumab) / Roche, MBQ-167 / MBQ Pharma, Perjeta (pertuzumab) / Roche
Targeting Rac/Cdc42 GTPases to overcome HER2-targeted therapy resistance (Section 11; Poster Board #6) - Mar 14, 2023 - Abstract #AACR2023AACR_5237;
MBQ-167 reduced Rac activity and downstream signaling, as well as cell viability with a GI50 of 78nM after 72 hours, while caspase activity was increased after 24 hours of treatment. The results presented herein show the utility of the Rac/Cdc42 inhibitor MBQ-167 in overcoming HER2-targeted therapy resistance.
- |||||||||| Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Tumor organoid based drug sensitivity testing in ovarian cancer identifies exceptional responders to targeted therapies (Section 44; Poster Board #9) - Mar 14, 2023 - Abstract #AACR2023AACR_4724;
This study demonstrates the utility of organoid based drug testing to identify potentially effective drugs and to guide treatment choice for patients with ovarian cancer. Tumor organoid based personalized treatments lead to extraordinary responses in several patients, including a patient in hospice care who responded to ibrutinib monotherapy and is still alive after 27 months.
- |||||||||| lapatinib / Generic mfg., irinotecan / Generic mfg., ibrutinib / Generic mfg.
A multiplex organoid avatar drug testing platform for precision medicine (Section 36; Poster Board #13) - Mar 14, 2023 - Abstract #AACR2023AACR_4457;
Patterns of drug response revealed unexpected common mechanisms. Future work will focus on informing patient care decisions with these results and determining if improvements in patient outcomes are realized.
- |||||||||| D3L-001 / D3 Bio
D3L-001, a novel bispecific antibody targeting HER2 and CD47, demonstrates potent preclinical efficacy in solid tumors. (Section 25; Poster Board #12) - Mar 14, 2023 - Abstract #AACR2023AACR_4019;
Many HER2-targeted drugs, including trastuzumab, pertuzumab, lapatinib, trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-DXd), have been approved for treatment of HER2-positive early and metastatic breast cancer (BC)...In both in vitro and in vivo studies using breast cancer HCC1954, JIMT-1 and gastric cancer N87 models, we observed a synergistic effect in the combination of Trastuzumab with Magrolimab...D3L-001 also displayed potent and comparable in vivo efficacy as Enhertu in gastric N87 model, and it showed synergistic in vivo efficacy, when combining with Pertuzumab or Paclitaxel, in breast HCC1954, JIMT-1 and gastric cancer N87 models. D3L-001, a novel HER2
- |||||||||| Targeting metabolic vulnerability in brain-metastatic HER2+ breast cancer (Section 20; Poster Board #29) - Mar 14, 2023 - Abstract #AACR2023AACR_2445;
Breast cancer patients harboring brain metastases are difficult to treat, and they suffer from severe symptoms impacting daily life and have poor survival rates. Our ultimate goal is to launch a clinical trial to test one or more of these drug combinations to provide an additional therapeutic option that may improve patients
- |||||||||| lapatinib / Generic mfg.
A Virtual Reality Adaptation of a Strategy for SemanticAssociation Memory (SESAME) Module: An Initial Feasibility andEfficacy Study () - Mar 10, 2023 - Abstract #SIRS2023SIR_167;
Nevertheless,our findings provide support for increased integration of VR-based cognitive remediation intoclinical care for individuals with psychotic-spectrum disorders, especially those experiencingpersistent cognitive deficits. Future research is also needed to investigate whether VR is associatedwith improved transfer of learned cognitive skills into everyday life.KeywordKeywordscognitive trainingvirtual realityverbal memorySemantic clusteringPoster Award YesPoster Award Eligibility - Young Investigator YesPoster Award Eligibility - SIRS Membership YesPlease list all co-authors for this poster submission.* Presenting AuthorFirst Name Last Name AffiliationSynthia * Guimond * The Royal's Institute of MentalHealth Research, University ofOttawaBryce Bogie University of Ottawa Faculty ofMedicineChelsea Noel The Royal's Institute of MentalHealth ResearchS
- |||||||||| Lynparza (olaparib) / Merck (MSD), AstraZeneca
Preclinical, Journal, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker: HROP68: A rare case of medullary pancreatic cancer-characterization and chemosensitivity of the first patient-derived cell line. (Pubmed Central) - Feb 10, 2023
This study illustrates the establishment of the first preclinical MPC models as well as the first in-depth characterization of an MPC PDCL. Since the scientific and clinical knowledge of this rare pancreatic cancer type is very limited, the presented models contribute to a better understanding of MPC and might be a valuable tool for the development of future treatment options.
- |||||||||| Kadcyla (ado-trastuzumab emtansine) / Roche, Perjeta (pertuzumab) / Roche
Review, Journal, PD(L)-1 Biomarker, IO biomarker, Metastases: Breakthroughs in the Systemic Treatment of HER2-Positive Advanced/Metastatic Gastric Cancer: From Singlet Chemotherapy to Triple Combination. (Pubmed Central) - Feb 9, 2023
HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.
- |||||||||| Preclinical, Journal: ROS is a master regulator of in vitro matriptase activation. (Pubmed Central) - Jan 31, 2023
Lastly, we demonstrate matriptase-directed NAC treatment results in apoptosis of several breast cancer cell lines either alone or in combination with clinically used therapeutics. These data demonstrate the contribution of ROS-mediated survival, its independence of kinase-mediated survival, and the plausibility of using matriptase activation to indicate the potential success of antioxidant therapy.
- |||||||||| lapatinib / Generic mfg., erlotinib / Generic mfg.
Journal: A novel transcription factor-based signature to predict prognosis and therapeutic response of hepatocellular carcinoma. (Pubmed Central) - Jan 24, 2023
Further enrichment and PPI analyses demonstrated that the 2-TF signature distinguished tumors into 2 clusters with proliferative and metabolic features, with the hub genes belonging to the former cluster. Our study identified a 2-TF prognostic signature that indicated tumor heterogeneity with different clinical features and treatment preference, which help optimal therapeutic strategy and improved survival for HCC patients.
- |||||||||| Journal, Gene Signature, IO biomarker: Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer. (Pubmed Central) - Jan 24, 2023
The IC50 values for rapamycin were higher in the low-risk group, whereas those for axitinib, AZD6244, erlotinib, GDC0941, GSK650394, GSK269962A, lapatinib, and PD0325901 were higher in the high-risk group. Therefore, the ubiquitination-related signature is considered a promising tool for predicting a BC patient's immunotherapy response.
- |||||||||| Herceptin (trastuzumab) / Roche, Perjeta (pertuzumab) / Roche
Retrospective data, Journal: Axillary Downstaging and the Impact of Clinical Axillary Status on Efficacy of Neoadjuvant Therapy for HER2-Positive Breast Cancer: A Network Meta-Analysis. (Pubmed Central) - Jan 21, 2023
The network meta-analysis of total-pCR showed that dual-target therapy is significantly better than single-target therapy in clinically node-positive patients, and carboplatin performed significantly better than anthracycline in single-target condition...However, lapatinib in combination with trastuzumab was ranked at the top in the clinically node-negative group, and pertuzumab showed dissatisfied performance in contrast to the primacy of pertuzumab in clinically node-positive groups...We highly recommended TCbHP as the first choice for the neoadjuvant treatment in clinically node-positive HER-2 positive breast cancer. Since lapatinib with trastuzumab ranked top in the clinically node-negative group, we looked forward to discovering the potential value of TKI in clinically node-negative patients, which needs further analysis in the future.
- |||||||||| Herceptin (trastuzumab) / Roche
Journal: PTX3 from vascular endothelial cells contributes to trastuzumab-induced cardiac complications. (Pubmed Central) - Jan 19, 2023
We identified a distinct mode of cardiotoxicity, wherein the activation of EGFR/STAT3 signalling by trastuzumab in VECs promotes PTX3 excretion, which contributes to the impaired contractility of cardiomyocytes by inhibiting cellular calcium signalling. We confirmed that lapatinib could be a feasible preventive agent against trastuzumab-induced cardiac complications and provided the rationale for the combined application of lapatinib and trastuzumab in cancer-therapy.
- |||||||||| Journal: Synthetic methodologies and SAR of quinazoline derivatives as PI3K inhibitors. (Pubmed Central) - Jan 18, 2023
Lapatinib, afatinib, gefitinib, erlotinib, idelalisib and copanlisib are quinazoline-based, FDA-approved PI3K inhibitors, while compounds like NVPBYL719, GDC-0032, AZD8186, AZD-6482, etc. are under different stages of clinical trials. In light of the above-mentioned facts, in the present study, we have reported different synthetic approaches, mechanisms of anticancer action, and structure-activity relationship analysis of reported quinazoline derivatives as PI3K inhibitors to help researchers working in the field in designing better and isoform-selective PI3K inhibitors.
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