The multiple roles and therapeutic potential of clusterin in non-small-cell lung cancer: a narrative review.
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ABSTRACT:
SUBMITTER: Tan J
PROVIDER: S-EPMC8264340 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and objectiveNon-small cell lung cancer (NSCLC) accounts for 80% of lung cancers and is the most common non-cutaneous cancer world-wide. In NSCLC, oligometastatic and oligoprogressive disease (OPD) have been recognized as separate entities within the realm of metastatic disease and are emerging concepts in the context of targeted systemic therapies. Our objectives are to discuss the current literature regarding the evolving definitions of OPD in the context of oligometastatic disease (OMD) for NSCLC. Further, to discuss current and future clinical trials that have shaped our local approach with stereotactic body radiation therapy (SBRT)/stereotactic ablative radiotherapy (SABR).MethodsLiterature on OPD in NSCLC and local ablative therapy (LAT) including SBRT/SABR and stereotactic radiosurgery (SRS) was reviewed.Key content and findingsOligoprogression is defined as limited (usually 3-5) metastatic areas progressing while on/off systemic therapy in the background of oligometastatic or polymetastatic disease. Prognosis in OPD with treatment (such as LAT and systemic therapy) may be more favorable. Outcomes for patients progressing on tyrosine kinase inhibitors (TKIs) with molecular mutations [such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)] who receive LAT are promising.ConclusionsPatients presenting with NSCLC metastasis with progression at a limited number of sites on/off a given line of systemic therapy may have favorable outcomes with aggressive LAT, which includes SBRT/SABR/SRS. Further studies need to be completed to further optimize treatment recommendations.
| S-EPMC9840049 | biostudies-literature
Project description:BackgroundSecreted clusterin (sCLU), a 75-80 kDa disulfide-linked heterodimeric protein, plays crucial roles in various pathophysiological processes, including lipid transport, tissue remodeling, cell apoptosis and reproduction. Our previous studies demonstrated that sCLU could influence cell apoptosis, proliferation, and invasion of non-small cell lung cancer (NSCLC) cells.MethodsIn this study, clusterin's function in regulating transdifferentiation of NSCLC cells was investigated. In addition, we examined the correlation between clusterin and clinicopathological features of lung cancer.ResultsWe found that clusterin was increased in lung adenocarcinoma tissues and decreased in lung squamous cell carcinoma tissues through immunohistochemical technique. In cultured lung adenocarcinoma cell lines, clusterin addition could increase SP-C protein expression in 2.75-fold, and decrease p63 protein expression in 0.65-fold (1.54 to 1). And also clusterin addition could increase SP-C mRNA expression in 4.05-fold, decreased p63 mRNA expression in 0.51-fold.ConclusionsOur study demonstrated that clusterin could promote EMT and influence transdifferentiation from lung squamous cell carcinoma to lung adenocarcinoma. However, we found that clusterin expression have no correlation with malignance associate clinicopathological data. Our study may help to further elucidate the development and progression of NSCLC, also it may contribute to the research of therapies targeting sCLU.
| S-EPMC5618728 | biostudies-literature
Project description:Preclinical and early clinical evidence suggest that radical radiotherapy of oligometastatic disease in non-small cell lung cancer (NSCLC) patients can impact outcomes with relatively limited toxicity. Whilst data from phase 2 randomized trials suggesting an improved overall survival (OS) with this treatment is promising, it has also illustrated the heterogeneity in this patient population and treatment. Oligometastatic disease in itself comprises a broad spectrum of patients, in terms of tumor load and location, stage of the disease and treatment history. This real-life variety in patient characteristics is often reflected in studies to a certain extent, hinting to the fact that all might benefit from radical radiotherapy to limited metastatic disease, yet leaving the question unanswered as to whom the ideal candidate is. Furthermore, differences between and within studies with regards to treatment modality, timing, radiation technique, and radiation dose are substantial. Also, preclinical and early clinical trials suggest that radiotherapy can work synergistically with checkpoint inhibitors by acting as an in situ cancer vaccine, therefore the combination of these two treatments in oligometastatic patients might entail the largest benefit. Ongoing randomized controlled phase 3 trials and prospective registry trials will further elucidate the true extent of benefit of this local treatment strategy and aid in identifying the ideal patient population and therapy. The current narrative review summarizes the clinical evidence on radiotherapy for oligometastatic NSCLC and highlights the remaining unknowns.
| S-EPMC8350107 | biostudies-literature
Project description:Background and objectiveBone metastases are common in patients with non-small cell lung cancer (NSCLC) and remain a significant source of morbidity, mortality, and diminished quality of life, despite the considerable progress made in the overall management of patients with metastatic NSCLC over the last decade. Understanding the molecular pathogenesis of bone metastases is critical to improving survival, preserving function, and managing symptoms in this patient population. The objective of our review is to provide a comprehensive review of the pathophysiology, clinical presentation, management, and factors predicting the development and prognosis of patients with NSCLC with bone metastases.MethodsAn online electronic search was performed on PubMed and Google Scholar of all English-language literature using combinations of the following keywords: bone metastases, non-small cell lung cancer, pathophysiology, skeletal related events, response to therapy, predictive factors, and immunotherapy. Bibliographies of identified papers were reviewed for additional articles of interest. Observational cohort, retrospective studies, randomized controlled trials (RCTs), meta-analyses, and review articles were examined for this review.Key content and findingsBone metastases in lung cancer patients remain a common occurrence, impacting morbidity, mortality, and quality of life. Patients with skeletal related events (SREs) have worse prognosis. There is data supporting use of bisphosphonates and/or denosumab, and these should be considered in all patients with bone metastases. Novel studies comparing the genomic alterations of skeletal metastases and primary tumors are needed. As therapy for patients with advanced disease evolves, more studies are needed to evaluate the interplay between immunotherapy and bone metastases, and in determining the response to treatment in bone.ConclusionsPredicting development and progression of bone metastases could allow earlier and targeted therapy in patients with bone metastases. Predicting and evaluating response to conventional chemotherapy and immune checkpoint inhibitors in NSCLC patients with bone metastases remains an unmet need and merits further study.
| S-EPMC9186248 | biostudies-literature
Project description:Radiotherapy, along with other loco-regional interventions, is conventionally utilized as a palliative approach to alleviate symptoms and mitigate oncological emergencies in advanced non-small cell lung cancer (NSCLC). Thanks to the ongoing improvement of medical treatments in the last decade, such as targeted therapy and immunotherapy, the survival of patients with advanced NSCLC has been considerably prolonged, making it feasible and clinically beneficial for radiotherapy to play a more active role in highly selected subpopulations. In this review, we will focus on the evolving roles of radiotherapy in advanced NSCLC. First of all, among patients who are initially unable to tolerate aggressive treatment due to severe symptoms caused by metastases and/or tumor emergencies, timely radiotherapy could significantly improve their performance status (PS) and general condition, thus giving them a chance for intensive treatment and prolonged survival. The efficacy, potential candidates, and optimal dose-fractionation regimens of radiotherapy in this clinical scenario will be discussed. Additionally, radiotherapy can play a curative role as a concurrent therapy, consolidation therapy, and salvage therapy for patients with oligo-metastatic, oligo-residual, and oligo-progressive disease, respectively. Accumulating evidence from recent clinical trials, basic research, and translational investigations regarding the potentially curative roles of radiotherapy in NSCLC patients with oligo-metastatic disease will be summarized. Moreover, with the advent of various small molecular tyrosine kinase inhibitors (TKIs), the treatment efficacy and overall survival of oncogene-addicted NSCLC with brain metastases have been significantly improved, and the clinical value and optimal timing of cranial radiotherapy have become topics of much debate. Finally, synergistic antitumor interactions between radiotherapy and immunotherapy have been repeatedly demonstrated. Thus, the immune sensitizing role of radiotherapy in advanced NSCLC is also highlighted in this review.
| S-EPMC7815368 | biostudies-literature
Project description:ObjectiveThe objectives of this review are to discuss: the definition, clinical and biologic features of oligometastatic non-small cell lung cancer (NSCLC), as well as the concept of treating oligoprogression in oligometastatic NSCLC.BackgroundA substantial proportion of patients diagnosed with lung cancer present with metastatic disease, and a large portion of patients who present with localized disease later develop metastases. Oligometastatic NSCLC is defined as an intermediate state between localized and widespread metastatic disease, where there may be a role for curative localized therapy approach by treating the primary tumor and all metastases with radiotherapy or surgery. Despite the increasing application of this approach in patients with lung cancer, the identification of patients who might benefit from this approach is yet to be well characterized.MethodsAfter a systematic review of the literature, a PubMed search was performed using the English language and the key terms: oligometastatic, non-small cell lung cancer (NSCLC), localized consolidative treatment (LCT), biomarkers, biologic features, clinical features. Over 500 articles were retrieved between 1889-2021. A total of 178 papers discussing the definition, clinical and biologic factors leading to oligometastatic NSCLC were reviewed and included in the discussion of this paper.ConclusionsOligometastatic NSCLC is a unique entity. Identifying patients who have oligometastatic NSCLC accurately using a combination of clinical and biologic features and treating them with localized consolidative approach appropriately results in improvement of outcome. Further understanding of the molecular mechanisms driving the formation of oligometastatic NSCLC is an important area of focus for future studies.
| S-EPMC8350108 | biostudies-literature
Project description:[This corrects the article DOI: 10.1371/journal.pone.0177146.].
| S-EPMC5549952 | biostudies-other
Project description:Pemetrexed is currently mainly considered for the treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) negative for gene mutations/rearrangements (wild-type disease (WTD)). This narrative review aimed to highlight the role of pemetrexed in the treatment of onco-driven nonsquamous advanced NSCLC by reviewing published clinical studies. For epidermal growth factor receptor (EGFR) mutations, patient survival following first-line pemetrexed-platinum was longer than for WTD. Later-line pemetrexed-based treatment after tyrosine kinase inhibitor (TKI) failure provided greater benefits than non-pemetrexed regimens. First- and later-line pemetrexed-based therapy also provided survival benefits in patients with anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearrangements. In patients with rearranged during transfection (RET) proto-oncogene rearrangements, survival with pemetrexed was similar to that in ALK- and ROS1-positive patients and longer than that in patients with Kirsten rat sarcoma (KRAS) virus proto-oncogene mutations or WTD, although the available studies were limited. For Erb-b2 receptor tyrosine kinase 2 (ERRB2) mutations, first-line pemetrexed showed outcomes similar to those for EGFR and KRAS alterations. Data on pemetrexed in patients with KRAS mutations or MNNG HOS-transforming (MET) expression were limited. Pemetrexed could be an option for first- and second-line treatment for TKI failure in nonsquamous advanced NSCLC with select targetable driver mutations.
| S-EPMC7563381 | biostudies-literature
Project description:Lung cancer is the leading cause of cancer-related death worldwide. Since prognosis of early-stage non-small cell lung cancer (NSCLC) remains dismal for common relapses after curative surgery, considerable efforts are currently focused on bringing immunotherapy into neoadjuvant and adjuvant settings. Previously, perioperative chemotherapy showed only a modest but significative improvement in overall survival. The presence of broad tumor neoantigens load at primary tumor prior to surgery as well as the known immunosuppressive status following resection represent the main rationale for immunotherapy in early disease. Several trials have been conducted in recent years, leading to atezolizumab and nivolumab approval in the adjuvant and neoadjuvant setting, respectively, and perioperative immunotherapy in NSCLC remains a field of active clinical and preclinical investigation. Unanswered questions in perioperative therapy in NSCLC include the optimal sequence and timing of chemotherapy and immunotherapy, the potential of combination strategies, the role of predictive biomarkers for patient selection and the choice of useful endpoints in clinical investigation.
| S-EPMC9735901 | biostudies-literature
Project description:Background and objectiveLung transplantation (LTx) in Japan has taken steps toward increasing the number of donors and recipients and is at the maturity stage of development, at which point pulmonologists (hereinafter referred to as "respirologists") become involved in transplant practice. Because of severe donor shortage and limited number of LTx surgeries, most of transplant process from candidacy evaluation to post-operative management has been handled only by thoracic surgeons, which takes away opportunities from respirologists to manage LTx recipients. Given the growth of both LTx and the number of patients with complex problems, cooperation with respirologists in transplant practice is urgently needed to achieve transplant success in Japan.MethodsAuthors summarized current transplant circumstance in Japan from the transplant physician's standpoint. A systematic search through PubMed database and Google Scholar was performed by terms of "respirologists", "pulmonologist", "lung transplant" or "Japan" from 2000 and 2022. Thoracic surgeons working at each transplant center were asked to complete a questionnaire on physicians' intervention to LTx.Key content and findingsThe roles of respirologists in LTx differ with facility size and function, depending on whether they are working at a non-transplant center with other respirologists or at a transplant center with transplant physicians. LTx centers are currently devoted to educating respirologists who work at non-transplant or low-volume transplant centers in order for them to deal with patients before and after transplantation.ConclusionsJoint efforts and training of outstanding personnel who can take care of recipients are required, this being the greatest issue for the success of transplantation in Japan.
| S-EPMC10586989 | biostudies-literature