Metal- and metalloid-based compounds to target and reverse cancer multidrug resistance DOI Creative Commons
Andreia Valente, Ana Podolski-Renić,

Isabella Poetsch

и другие.

Drug Resistance Updates, Год журнала: 2021, Номер 58, С. 100778 - 100778

Опубликована: Авг. 6, 2021

Drug resistance remains the major cause of cancer treatment failure especially at late stage disease. However, based on their versatile chemistry, metal and metalloid compounds offer possibility to design fine-tuned drugs circumvent even specifically target drug-resistant cells. Based paramount importance platinum in clinics, two main areas drug reversal strategies exist: overcoming as well multidrug ABC efflux pumps. The current review provides an overview both aspects discusses open questions field. covered this article involve: 1) Altered expression proteins involved uptake, or intracellular distribution, 2) Enhanced via transporters, 3) metabolism cells, 4) thiol redox homeostasis, 5) DNA damage recognition enhanced repair, 6) Impaired induction apoptosis 7) interaction with immune system. This represents first collection (including platinum, ruthenium, iridium, gold, copper) (e.g. arsenic selenium) which demonstrated activity. A special focus is characterized by collateral sensitivity transporter-overexpressing Through approach, we wish draw attention research Future investigations are warranted obtain more insights into mechanisms action most potent specific modalities resistance.

Язык: Английский

First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial DOI
Luis Paz‐Ares, Tudor–Eliade Ciuleanu, Manuel Cobo

и другие.

The Lancet Oncology, Год журнала: 2021, Номер 22(2), С. 198 - 211

Опубликована: Янв. 19, 2021

Язык: Английский

Процитировано

1103
The Next Decade of Immune Checkpoint Therapy DOI Open Access
Padmanee Sharma, Bilal A. Siddiqui, Swetha Anandhan

и другие.

Cancer Discovery, Год журнала: 2021, Номер 11(4), С. 838 - 857

Опубликована: Апрель 1, 2021

Immune checkpoint therapy (ICT) can provide durable clinical responses and improve overall survival. However, only subsets of patients with specific tumor types respond to ICT. Thus, significant challenges remain, including understanding pathways resistance, optimizing patient selection, improving management immune-related adverse events, identifying rational therapeutic combinations. These will need a focused approach encompassing both basic research, the integration reverse translational studies. This integrated lead identification potential targets for subsequent trials, which guide decisions as we develop novel combination strategies maximize efficacy minimize toxicities patients. SIGNIFICANCE: ICTs induce antitumor cancer. Recent evidence suggests that combinatorial response by overcoming primary adaptive resistance mechanisms, although these may carry an increased risk immune-mediated toxicities. review surveys current mechanisms active areas investigation, proposes path forward minimizing through better selection

Язык: Английский

Процитировано

557
Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance DOI
Nuray Erin, Jelena Grahovac, Anamaria Brozović

и другие.

Drug Resistance Updates, Год журнала: 2020, Номер 53, С. 100715 - 100715

Опубликована: Июнь 20, 2020

Язык: Английский

Процитировано

399
Radiotherapy combined with immunotherapy: the dawn of cancer treatment DOI Creative Commons

Zengfu Zhang,

Xu Liu,

Dawei Chen

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июль 29, 2022

Abstract Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which called abscopal effect. The view RT as a simple treatment has dramatically changed in recent years, it now widely accepted that provoke immune response gives strong rationale the combination immunotherapy (iRT). Nevertheless, several points remain to be addressed such interaction system, identification best schedules with (IO), expansion mechanism amplify iRT. To answer these crucial questions, we roundly summarize underlying showing whole landscape clinical trials attempt identify In consideration rarity effect, propose occurrence induced by radiation promoted 100% molecular genetic level. Furthermore, “radscopal effect” refers using low-dose reprogram microenvironment may overcome resistance Taken together, could regarded trigger antitumor response, help IO used radical added into current standard regimen patients metastatic cancer.

Язык: Английский

Процитировано

380
Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons DOI Creative Commons
Adel Naimi, Rebar N. Mohammed, Ahmed Raji

и другие.

Cell Communication and Signaling, Год журнала: 2022, Номер 20(1)

Опубликована: Апрель 7, 2022

Abstract The main breakthrough in tumor immunotherapy was the discovery of immune checkpoint (IC) proteins, which act as a potent suppressor system by myriad mechanisms. After that, scientists focused on molecules mainly. Thereby, much effort spent to progress novel strategies for suppressing these inhibitory axes, resulting evolution inhibitors (ICIs). Then, ICIs have become promising approach and shaped paradigm shift immunotherapies. CTLA-4 plays an influential role attenuation induction naïve memory T cells engagement with its responding ligands like B7-1 (CD80) B7-2 (CD86). Besides, PD-1 is predominantly implicated adjusting cell function peripheral tissues through interaction programmed death-ligand 1 (PD-L1) PD-L2. Given their suppressive effects anti-tumor immunity, it has firmly been documented that based therapies can be practical rational therapeutic approaches treat cancer patients. Nonetheless, inherent or acquired resistance ICI some treatment-related toxicities restrict application clinic. current review will deliver comprehensive overview human tumors alone combination other modalities support more desired outcomes lower

Язык: Английский

Процитировано

296
Targeting the ubiquitin-proteasome pathway to overcome anti-cancer drug resistance DOI

Silpa Narayanan,

Chao‐Yun Cai,

Yehuda G. Assaraf

и другие.

Drug Resistance Updates, Год журнала: 2019, Номер 48, С. 100663 - 100663

Опубликована: Ноя. 11, 2019

Язык: Английский

Процитировано

257
Medicinal chemistry strategies to discover P-glycoprotein inhibitors: An update DOI
Jinyun Dong, Zuodong Qin, Weidong Zhang

и другие.

Drug Resistance Updates, Год журнала: 2020, Номер 49, С. 100681 - 100681

Опубликована: Янв. 22, 2020

Язык: Английский

Процитировано

215
Hypoxia as a driver of resistance to immunotherapy DOI
Joanna Kopecka, Iris C. Salaroglio, Elisabeth Pérez-Ruíz

и другие.

Drug Resistance Updates, Год журнала: 2021, Номер 59, С. 100787 - 100787

Опубликована: Ноя. 18, 2021

Язык: Английский

Процитировано

183
Cancer immunotherapy resistance based on immune checkpoints inhibitors: Targets, biomarkers, and remedies DOI Creative Commons
Elisabeth Pérez-Ruíz, Ignacio Melero, Joanna Kopecka

и другие.

Drug Resistance Updates, Год журнала: 2020, Номер 53, С. 100718 - 100718

Опубликована: Июль 15, 2020

Cancer is one of the main public health problems in world. Systemic therapies such as chemotherapy and more recently target well immunotherapy have improved prognosis this large group complex malignant diseases. However, frequent emergence multidrug resistance (MDR) mechanisms major impediments towards curative treatment cancer. While several drug chemoresistance are defined, to still insufficiently unclear due complexity immune response its dependence on host. Expression regulation checkpoint molecules (such PD-1, CD279; PD-L1, CD274; CTLA-4, CD152) play a key role immunotherapy. In regard, based checkpoints inhibitors (ICIs) common clinical approach for patients with poor when other first-line failed. Unfortunately, about 70 % classified non-responders, or they progress after initial these ICIs. Multiple factors can be related resistance: characteristics tumor microenvironment (TME); presence infiltrating lymphocytes (TILs), CD8 + T cells associated treatment-response; macrophages (TAMs); activation certain regulators (like PIK3γ PAX4) found present non-responders; low percentage PD-L1 expressing cells; mutational burden (TMB); gain loss antigen-presenting molecules; genetic epigenetic alterations correlated resistance. This review provides an update current state presenting targets, biomarkers remedies overcome

Язык: Английский

Процитировано

167
Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs DOI Creative Commons
Ran Qi,

Yixuan Bai,

Kun Li

и другие.

Drug Resistance Updates, Год журнала: 2023, Номер 68, С. 100960 - 100960

Опубликована: Март 28, 2023

Pancreatic cancer continues to be one of the world's most lethal cancers. Chemotherapy resistance in patients with advanced pancreatic often accompany dismal prognosis, highlighting need investigate mechanisms drug and develop therapies overcome chemoresistance.This research was filed Chinese Clinical Trial Registry (ChiCTR2200061320). In order isolate primary normal fibroblasts (NFs) cancer-associated (CAFs) samples ductal adenocarcinoma (PDAC) paracancerous tissue from individuals diagnosed PDAC were obtained. The exosomes obtained using ultracentrifugation, their characteristics determined by Western blotting, nanoparticle tracking analysis, transmission electron microscopy. CAF-derived miRNAs analyzed RT-qPCR high-throughput sequencing. Gemcitabine (GEM) employed promote ferroptosis, ferroptosis levels monitoring lipid reactive oxygen species (ROS), cell survival, intracellular Fe2+ concentrations. To assess vivo tumor response GEM therapy, a xenograft mouse model utilized.Exosomes derived CAFs did not exhibit innate resistance. promoted chemoresistance cells following treatment secreting exosomes, maintaining signaling communication cells. Mechanistically, miR-3173-5p CAF sponged ACSL4 inhibited after uptake cells.This work demonstrates novel mode acquired identifies miR-3173-5p/ACSL4 pathway as promising target for GEM-resistant cancer.

Язык: Английский

Процитировано

156