Targeting drug-resistant mutations in ALK.

Nat Cancer

Department of Oncological Sciences, The Tisch Cancer Institute, Mount Sinai Centre for Therapeutic Discovery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Published: June 2022

Therapy resistance limits the clinical success of tyrosine kinase inhibitors (TKIs) in ALK-positive non-small cell lung cancer. A study now proposes a framework to identify compound resistance mutations to the lorlatinib TKI and provides structure-based drug design approaches to overcome resistance mediated by ALK(G1202R) or ALK(I1171N/S/T).

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9919885PMC
http://dx.doi.org/10.1038/s43018-022-00390-1DOI Listing

Publication Analysis

Top Keywords

targeting drug-resistant
4
drug-resistant mutations
4
mutations alk
4
alk therapy
4
therapy resistance
4
resistance limits
4
limits clinical
4
clinical success
4
success tyrosine
4
tyrosine kinase
4

Similar Publications

Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.

View Article and Find Full Text PDF

Omega-3 fatty acids: molecular weapons against chemoresistance in breast cancer.

Cell Mol Biol Lett

January 2025

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata Di Rende, 87036, Cosenza, Italy.

Breast cancer is the most commonly diagnosed type of cancer and the leading cause of cancer-related death in women worldwide. Highly targeted therapies have been developed for different subtypes of breast cancer, including hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, triple-negative breast cancer (TNBC) and metastatic breast cancer disease are primarily treated with chemotherapy, which improves disease-free and overall survival, but does not offer a curative solution for these aggressive forms of breast cancer.

View Article and Find Full Text PDF

Background: Oral squamous cell carcinoma (OSCC) ranks as the sixth most common malignancy globally. Cisplatin is the standard chemotherapy for OSCC, but resistance often reduces its efficacy, necessitating new treatments with fewer side effects. Rumex dentatus L.

View Article and Find Full Text PDF

Acute B-lymphoblastic leukemia (B-ALL) is a highly heterogeneous hematologic malignancy, characterized by significant molecular differences among patients as the disease progresses. While the PI3K-Akt signaling pathway and metabolic reprogramming are known to play crucial roles in B-ALL, the interactions between lipid metabolism, immune pathways, and drug resistance remain unclear. In this study, we performed multi-omics analysis on different patient cohorts (newly diagnosed, relapsed, standard-risk, and poor-risk) to investigate the molecular characteristics associated with metabolism, signaling pathways, and immune regulation in B-ALL.

View Article and Find Full Text PDF

A safe haven for cancer cells: tumor plus stroma control by DYRK1B.

Oncogene

January 2025

Department of Gastroenterology, Endocrinology and Metabolism, Center for Tumor and Immune Biology, Philipps University Marburg, Marburg, Germany.

The development of resistance remains one of the biggest challenges in clinical cancer patient care and it comprises all treatment modalities from chemotherapy to targeted or immune therapy. In solid malignancies, drug resistance is the result of adaptive processes occurring in cancer cells or the surrounding tumor microenvironment (TME). Future therapy attempts will therefore benefit from targeting both, tumor and stroma compartments and drug targets which affect both sides will be highly appreciated.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!