- |||||||||| Irene (pyrotinib) / Jiangsu Hengrui Pharma
Review, Journal: Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer. (Pubmed Central) - Jun 5, 2023 Recently, the use of tyrosine kinase inhibitors (TKIs) has been of particular interest in the treatment of human malignancies. This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.
- |||||||||| Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Journal: Dissecting sources of variability in patient response to targeted therapy: anti-HER2 therapies as a case study. (Pubmed Central) - May 29, 2023 The results showed that the synthesized nanohydrogels significantly inhibited the expression of EGFP-kras oncogene in zebrafish liver, and the L-arginine modified OCMC-g-Suc-?-CD nanohydrogels loading lapatinib and ginsenoside Rg1 showed the best results. The platform can dissect sources of variability in response to target therapy, which may facilitate decision-making during drug development.
- |||||||||| Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca
P3 data, Journal, Metastases: Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. (Pubmed Central) - May 29, 2023 P3 The platform can dissect sources of variability in response to target therapy, which may facilitate decision-making during drug development. DESTINY-Breast02 shows the favourable benefit-risk profile of trastuzumab deruxtecan in patients with HER2 positive metastatic breast cancer, as previously reported in DESTINY-Breast01, and is the first randomised study to show that one antibody-drug conjugate can overcome resistance to a previous one.
- |||||||||| Kadcyla (ado-trastuzumab emtansine) / Roche, Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca, Perjeta (pertuzumab) / Roche
Review, Journal, Metastases: History and Future of HER2-Targeted Therapy for Advanced Gastric Cancer. (Pubmed Central) - May 27, 2023 Recently, a novel anti-HER2 agent, trastuzumab deruxtecan, was introduced, and the development of HER2-positive gastric cancer agents has been moving to the next stage. This review summarizes the current HER2-targeted therapy for gastric or gastroesophageal cancer in chronological order and describes the promising future of HER2-targeted therapy.
- |||||||||| Farydak (panobinostat) / Secura Bio
Review, Journal: Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy. (Pubmed Central) - May 16, 2023 Some examples are: bipolar androgen therapy (BAT) and drugs such as indomethacin, niclosamide, lapatinib, panobinostat, clomipramine, metformin, and antisense oligonucleotides. All of them have shown, in addition to an inhibitory effect on PCa, the rewarding ability to overcome acquired resistance to antiandrogenic agents in CRPC, resensitizing the tumor cells to previously used ARSis.
- |||||||||| Herceptin (trastuzumab) / Roche
Journal: Long-term outcomes of dual vs single HER2-directed neoadjuvant therapy in NSABP B-41. (Pubmed Central) - May 15, 2023 P3 Although pCR, RFI, and OS were numerically better with the dual combination and less with L, the differences were not statistically significant. However, achievement of pCR again correlated with improved outcomes, especially remarkable in the ER-negative subset.
- |||||||||| Kadcyla (ado-trastuzumab emtansine) / Roche, Perjeta (pertuzumab) / Roche
Review, Journal: Radiotherapy and targeted therapy for the management of breast cancer: A review (Pubmed Central) - May 13, 2023 Moreover, there is a great heterogeneity between these studies regarding the dose and fractionation used in radiotherapy, the dosage of systemic treatments and the sequence of treatments used. Therefore, the combination of these new molecules with radiotherapy should be proposed sparingly, under close monitoring, pending the ongoing prospective studies cited in this review.
- |||||||||| oxaliplatin / Generic mfg., lapatinib / Generic mfg., capecitabine / Generic mfg.
Trial completion date, Metastases: LOGiC - Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib (clinicaltrials.gov) - May 12, 2023 P3, N=545, Active, not recruiting, Therefore, the combination of these new molecules with radiotherapy should be proposed sparingly, under close monitoring, pending the ongoing prospective studies cited in this review. Trial completion date: Aug 2023 --> Dec 2023
- |||||||||| Review, Journal: BRD4: New Hope in the Battle Against Glioblastoma. (Pubmed Central) - May 8, 2023
In addition, several BRD4 inhibitors have been evaluated for therapeutic purposes as monotherapy or in combination with chemotherapy, radiotherapy, and immune therapies. Here, we provide a critical appraisal of studies evaluating various BRD4 inhibitors and degraders as novel treatment strategies against GBM.
- |||||||||| Review, Journal: Structure-Activity Relationship Studies Based on Quinazoline Derivatives as EGFR Kinase Inhibitors (2017-Present). (Pubmed Central) - Apr 28, 2023
Currently, there are five first-generation (gefitinib, erlotinib, lapatinib, vandetanib, and icotinib) and two second-generation (afatinib and dacomitinib) quinazoline-based EGFR inhibitors approved for the treatment of various types of cancers. The aim of this review is to outline the structural modulations favorable for the inhibitory activity toward both common mutant (del19 and L858R) and resistance-conferring mutant (T790M and C797S) EGFR forms, and provide an overview of the newly synthesized quinazoline derivatives as potentially competitive, covalent or allosteric inhibitors of EGFR.
- |||||||||| Evolution of breast cancer management in the Dominican Republic in the 21st century. () - Apr 26, 2023 - Abstract #ASCO2023ASCO_4119;
It highlights the efforts made to apply guidelines on breast cancer management in general and global objective response to neoadjuvant regimen. It also highlights the need to implement more primary prevention and early detection since 52% of patients belong to the locally advanced category.
- |||||||||| Herceptin (trastuzumab) / Roche
Association of HER2/CEP17 ratio with pCR after HER2-directed neoadjuvant treatments in the phase III NeoALTTO trial. (Available On Demand; Poster Bd # 430) - Apr 26, 2023 - Abstract #ASCO2023ASCO_988; 455 women with HER2-positive early breast cancer, who had received neo-adjuvant trastuzumab and/or lapatinib for 6 weeks and then together with 12 cycles of weekly paclitaxel were included in this analysis. In patients treated with HER2-based neoadjuvant therapy, quantitative analysis of the readily available pre-treatment HER2/CEP17 ratio by FISH is predictive of pCR but not EFS.
- |||||||||| lapatinib / Generic mfg.
Journal: Synthesis and Anticancer Evaluation of 4-Anilinoquinolinylchalcone Derivatives. (Pubmed Central) - Apr 13, 2023 Compound 4a causes ATP depletion and apoptosis of breast cancer MDA-MB-231 cells and triggers reactive oxygen species (ROS)-dependent caspase 3/7 activation. In conclusion, it is worth studying 4-anilinoquinolinylchalcone derivatives further as new potential anticancer agents for the treatment of human cancers.
- |||||||||| Review, Journal, IO biomarker: Emerging Targeted Therapies for HER2-Positive Breast Cancer. (Pubmed Central) - Apr 13, 2023
When patients progress to multiple strategies, there are several HER2-targeted therapies available; however, treatment options are limited, and the potential combination with other drugs, immune checkpoint inhibitors, CAR-T cells, CAR-NK, CAR-M, and vaccines is an interesting and appealing field that is still in development. In this review, we will discuss the highlights and pitfalls of the different HER2-targeted therapies and potential combinations to overcome metastatic disease and resistance to therapy.
- |||||||||| MK-2206 / Merck (MSD), Koselugo (selumetinib) / Merck (MSD), AstraZeneca
Enrollment change, Metastases: Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies (clinicaltrials.gov) - Apr 11, 2023 P2, N=647, Active, not recruiting, In this review, we will discuss the highlights and pitfalls of the different HER2-targeted therapies and potential combinations to overcome metastatic disease and resistance to therapy. N=471 --> 647
- |||||||||| Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca
ENHERTU, THE GAME CHANGER IN HER2+ MBC TREATMENT: FROM CLINICAL TRIAL TO CLINICAL PRACTICE (RM 1 (Vista 1+2)) - Apr 4, 2023 - Abstract #GBCC2023GBCC_21; When the factors affecting the prognosis were evaluated, we determined that the largest size of brain metastasis, estrogen receptor positivity, and the use of TDM-1 and lapatinib plus capecitabine consecutively during the treatment process affected the prognosis of the disease. The HER2-positive metastatic breast cancer is majorly incurable disease despite the use of HER2- targeting agents, such as trastuzumab, pertuzumab, and lapatinib, because of frequent drug resistance, and patients eventually die from the breast cancer after several lines of systemic chemotherapy...In Destiny Breast02 trial, 608 HER2-positive metastatic breast cancer patients who were previously treated with T-DM1 received T-DXd (experimental) or treatment of physician
- |||||||||| TARGETING HER2-LOW AND THE TREATMENT SEQUENCE (RM 1 (Vista 1+2)) - Apr 4, 2023 - Abstract #GBCC2023GBCC_7;
After a long journey, the HER2-directed therapy with trastuzumab deruxtecan finally crosses the boundary set for other anti-HER2 agents and establishes its efficacy in HER2-low breast cancer. In the near future, we may anticipate the development of strategies or drugs for patients with HER2-low breast cancer.
- |||||||||| lapatinib / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Journal, Metastases: Glycol chitosan (Pubmed Central) - Mar 28, 2023 The combination nanomedicine significantly inhibited both the primary 4T1 breast tumor and its spread to the lung, liver, heart, and kidney compared to pristine drug controls. These preliminary data indicate bright prospects for the nanomedicine to be effective against metastatic breast cancer.
- |||||||||| lapatinib / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Journal: Membrane fusion-mediated delivery of small-molecule inhibitor for effective tumor chemosensitization. (Pubmed Central) - Mar 25, 2023 Here, we developed a small-molecule tyrosine kinase inhibitor (TKI)- and doxorubicin (Dox, a common anticancer drug)-loaded membrane fusion liposome (MFL) (termed Dox@Lapa-MFL) to achieve tumor cell membrane fusion-mediated drug delivery and enhanced chemotherapy of drug-resistant tumor...Lapatinib, as the TKI doped in the MFL, could inhibit the efflux of Dox by ATP-binding cassette transporters (ABC transporters), further promoting the intracellular Dox accumulation...To the best of our knowledge, it is the first example that employs membrane fusion-mediated TKI delivery for achieving tumor chemosensitization with good biosafety. This work presents an efficient and easily achievable strategy for treating drug-resistant tumors, which may hold promise for clinical applications.
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