drug resistance cancer

Atogepant, an oral calcitonin gene-related peptide receptor antagonist, is approved for the preventive treatment of migraine. Atogepant is a substrate of P-glycoprotein (P-gp), breast cancer resistance protein, organic anion transporting polypeptide transporters, and cytochrome P450 (CYP)3A4 and 2D6. Quinidine is a strong P-gp and CYP2D6 inhibitor. A phase 1 open-label study evaluated the effect of P-gp and CYP2D6 inhibition by quinidine on the pharmacokinetics of atogepant, and the safety and tolerability of atogepant and quinidine gluconate (QG) when co-administered and when given alone in 33 healthy adults...

Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy. This comprehensive review examines the complex relationship between USPs and drug resistance mechanisms, focusing on specific treatment strategies and highlighting the influence of USPs on DNA damage repair, apoptosis, characteristics of cancer stem cells, immune evasion, and other crucial biological functions...

Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure...

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies...

INTRODUCTION: Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system and accounts for more than 90 % of all renal tumors. Resistance to targeted therapy has emerged as a pivotal factor that contributes to the progressive deterioration of patients with advanced RCC. Metabolic reprogramming is a hallmark of tumorigenesis and progression, with an increasing body of evidence indicating that abnormal lipid metabolism plays a crucial role in the advancement of renal clear cell carcinoma...

The combination of radiation treatment and chemotherapy is currently the standard for management of cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat treatment with often already increased tumor resistance to drugs and irradiation. One of the solutions we suggest is to improve primary course of radiation treatment via enhancing radiosensitivity of tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized iron oxide nanoparticles (hIONPs, ∼20 nm), characterized it by TEM, Infrared spectroscopy and DLS...

Gliomas are the most common type of malignant brain tumors, with glioblastoma multiforme (GBM) having a median survival of 15 months due to drug resistance and relapse. The treatment of gliomas relies on surgery, radiotherapy and chemotherapy. Only 12 anti-brain tumor chemotherapies (AntiBCs), mostly alkylating agents, have been approved so far. Glioma subtype-specific metabolic models were reconstructed to simulate metabolite exchanges, in silico knockouts and the prediction of drug and drug combinations for all three subtypes...

Ovarian cancer is an aggressive gynecological tumor characterized by a high relapse rate and chemoresistance. Ovarian cancer exhibits the cancer hallmark of elevated glycolysis, yet effective strategies targeting cancer cell metabolic reprogramming to overcome therapeutic resistance in ovarian cancer remain elusive. Here, we revealed that epigenetic silencing of Otubain 2 ( OTUB2 ) is a driving force for mitochondrial metabolic reprogramming in ovarian cancer, which promotes tumorigenesis and chemoresistance...

Hepatocellular carcinoma (HCC), one of the most prevalent and destructive causes of cancer-related deaths worldwide, approximately 70% of patients with HCC exhibit advanced disease at diagnosis, limiting the potential for radical treatment. For such patients, lenvatinib, a long-awaited alternative to sorafenib for first-line targeted therapy, has become a key treatment. Unfortunately, despite some progress, the prognosis for advanced HCC remains poor because of drug resistance development. However, the molecular mechanisms underlying lenvatinib resistance and ways to relief drug resistance in HCC are largely unknown and lack of systematic summary; thus, this review not only aims to explore factors contributing to lenvatinib resistance in HCC, but more importantly, summary potential methods to conquer or mitigate the resistance...

BACKGROUND: The current treatment strategy for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) is the combination of Androgen Receptor Signaling Inhibitors (ARSIs) medicines with androgen deprivation therapy (ADT). However, there is a lack of real-world data comparing the efficacy of different ARSI pharmaceuticals. Therefore, the objective of this study was to compare the effectiveness and safety of bicalutamide, abiraterone, enzalutamide, and apalutamide in combination with ADT for patients with mHSPC...

Non-small cell lung cancer (NSCLC) caused more deaths in 2017 than breast cancer, prostate, and brain cancers combined. This is primarily due to their aggressive metastatic nature, leading to more fatal rates of cancer patients. Despite this condition, there are no clinically approved drugs that can target metastasis. The NSCLC with EGFR T790M-overexpressing HER2 shows the resistance to osimertinib and trastuzumab starting 10-18 months after the therapy, and thus prospects are grim to these patients. To target the recalcitrant ERBB2 driver oncogene, we developed two engineered destabilizing 3'UTR ERBB2 constructs that degrade the endogenous ERBB2 transcript and proteins by overwriting the encoded endogenous ERBB2 mRNA with the destabilizing message...

BACKGROUND: Iruplinalkib is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) with efficacy in patients with ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC), which is independently developed by a Chinese pharmaceutical company. This study examined the cost-effectiveness of iruplinalkib versus alectinib in the Chinese healthcare setting. METHODS: A partitioned survival model was developed to project the economic and health outcomes...

In recent years, castration-resistant prostate cancer (CRPC) has profoundly impacted the lives of many men, and early diagnosis of medication and illness is crucial. Therefore, a highly efficient detection method for CRPC biomarkers and curing drugs is required. However, the complex and diverse structures of CRPC drugs pose significant challenges for their detection and differentiation. Lanthanide metal-organic frameworks (Ln-MOFs) show great potential for sensing applications due to their intense and characteristic luminescence...

Breast cancers (BRCA) exhibit substantial transcriptional heterogeneity, posing a significant clinical challenge. The global transcriptional changes in a disease context, however, are likely mediated by few key genes which reflect disease etiology better than the differentially expressed genes (DEGs). We apply our network-based tool PathExt to 1,059 BRCA tumors across 4 subtypes to identify key mediator genes in each subtype. Compared to conventional differential expression analysis, PathExt-identified genes exhibit greater concordance across tumors, revealing shared and subtype-specific biological processes; better recapitulate BRCA-associated genes in multiple benchmarks, and are more essential in BRCA subtype-specific cell lines...

The prevalence of skin disorders, especially cancer, is increasing worldwide. Several factors are involved in causing skin cancer, but ultraviolet (UV) light, including sunlight and tanning beds, are considered the leading cause. Different methods such as chemotherapy, radiotherapy, cryotherapy, and photodynamic therapy are mostly used for the skin cancer treatment. However, drug resistance and toxicity against cancer cells are related to these treatments. Lipid-nanoparticles have attracted significant interest as delivery systems due to non-invasive and targeted delivery based on the type of active drug...

BACKGROUND: The Y-box-binding proteins (YBX) act as a multifunctional role in tumor progression, metastasis, drug resistance by regulating the transcription and translation process. Nevertheless, their functions in a pan-cancer setting remain unclear. METHODS: This study examined the clinical features expression, prognostic value, mutations, along with methylation patterns of three genes from the YBX family (YBX1, YBX2, and YBX3) in 28 different types of cancer...

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Natural plant sources are essential in the development of several anticancer drugs, such as vincristine, vinblastine, vinorelbine, docetaxel, paclitaxel, camptothecin, etoposide, and teniposide. However, various chemotherapies fail due to adverse reactions, drug resistance, and target specificity. Researchers are now focusing on developing drugs that use natural compounds to overcome these issues. These drugs can affect multiple targets, have reduced adverse effects, and are effective against several cancer types...

AIM: To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. METHODS: From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed...

BACKGROUND: Comparative investigations evaluating the efficacy of pomalidomide-based (Pom-based) versus daratumumab-based (Dara-based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real-world studies. METHODS: This retrospective cohort study included 140 RRMM patients treated with Pom-based or Dara-based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023...