Subsequent thoracic cancers among patients diagnosed with lung cancer: a SEER database analysis

Background: Population-based data on the development of subsequent thoracic cancers following the initial diagnosis of lung cancer are scarce. We evaluated this clinical scenario in lung cancer patients registered within the Surveillance, Epidemiology and End Results (SEER) database.

Methods: The SEER database (1988–2013) was queried using the SEER*Stat program to determine the clinico-pathological features of lung cancer patients who develop subsequent thoracic cancers as well as the characteristics of these subsequent cancers. Associations were ascertained with chi-squared tests and survival analysis was performed using Kaplan–Meier methods. Standardized incidence ratios (SIRs) were calculated to determine the risk of each type of subsequent cancer.

Results: A total of 223,274 lung cancer patients were identified and included in the current study. In this cohort, 6387 patients developed subsequent thoracic cancers. The following were associated with a higher likelihood of second cancers: female gender, younger age, white race, adenocarcinoma histology, married, lower AJCC stage, earlier year of diagnosis and local treatment with surgery rather than radiotherapy (p?p?p?Conclusion: There is an excess risk for the development of esophageal cancer and second primary lung cancer following an initial lung cancer diagnosis. This risk is present irrespective of gender or receipt of radiotherapy.     

Targeting the PD-1 pathway: a new hope for gastrointestinal cancers

Background: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aim to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in published or reported recent studies.

Scope: A literature search was made from PubMed and ASCO Annual Meeting abstracts by using the following search keywords: “nivolumab”, “pembrolizumab”, “avelumab”, “GI cancers” “anti-PD1 therapy” and “anti-PD-L1 therapy”. The last search was on 2 November 2016. The most important limitation of our review is that most of the data on anti-PD-1/PD-L1 therapies in GI cancers relies on phase 1 and 2 trials.

Findings: Currently, there are two anti-PD-1 (nivolumab and pembrolizumab) and one anti-PDL1 (atezolizumab) agents approved by FDA. After the treatment efficacy of immune checkpoint blockade was shown in melanoma, renal cell cancer and non-squamous lung cancer, trials which evaluate immune checkpoint blockade in GI cancers are ongoing. Early results of trials have been promising and encouraging for patients with advanced stage gastroesophageal cancer. According to early results of published trials, response to anti-PD1/PD-L1 agents appears to be associated with tumor PD-L1 levels. According to two recently published phase 2 trials, the clinical benefits of immune checkpoint blockade with both nivolumab and pembrolizumab were limited in patients with microsatellite instability (MSI) positive advanced colorectal cancer. However, several phase 2/3 trials are still ongoing.

Conclusion: Both pembrolizumab and nivolumab show promising efficacy with acceptable safety data in published trials in GI cancers, especially in refractory MSI positive metastatic colorectal cancer.     

Immunotherapy for gastric cancers: emerging role and future perspectives

Introduction: The broad use of immunotherapy is revolutionizing the treatment paradigms of many solid tumors. Although chemotherapy remains the treatment backbone for advanced gastric cancer, improvements in its molecular characterization and progresses in understanding its underpinning biology have supported clinical development of novel immunotherapies. However, the results of recent trials testing these new agents raise the question on how to identify the patients that could greatly benefit.

Areas covered: This article summarizes the current understanding on the biology and the mechanisms underlying different clinical features of gastric cancers. Particularly, after a comprehensive literature search, we speculate whether specific molecular subsets of patients could derive more benefit from immunotherapy.

Expert commentary: Most cancers may evade the immune response, which is normally regulated by a delicate balance between activating and inhibitory signals. For example, both CTLA-4 and PD-1, once linked to PD-L1/2, may inhibit T-cell signaling. The use of agent to harness the power of the immune system appears to be the ultimate frontier in gastric cancer treatment. While anti-CTLA-4 antibodies are minimally active, there is growing evidence for the efficacy of PD1/-L1 inhibitors. The search of predictive factors for immunotherapy will provide key hints towards the optimal use of these agents.     

Overview of different available chemotherapy regimens combined with radiotherapy for the neoadjuvant and definitive treatment of esophageal cancer

Introduction: Neoadjuvant chemoradiotherapy (CTRT) is the current standard of care for treatment of locally advanced cancer of the esophagus or gastroesophageal junction. Many efforts have been made over the last years to identify the best chemotherapy and radiotherapy combination regimen, but specific randomized trials addressing this issue are still lacking.

Areas covered: A systematic review of the literature was performed searching in PubMed all published studies of combinations CTRT regimens for operable or unresectable esophageal cancer to describe activity and toxicity. Studies considered were prospective series or clinical phase II-III trials including at least 40 patients and published in English language.

Expert commentary: Long-term results of CROSS trial have established RT combined with carboplatin plus paclitaxel chemotherapy as the preferred neoadjuvant treatment option for both squamous and adenocarcinoma of the esophagus. More effective multimodal treatment strategies integrating novel biological agents including immunotherapy and based on an extensive molecular tumor characterization are eagerly awaited.     

Ramucirumab for the treatment of gastric cancers,colorectal adenocarcinomas,and other gastrointestinal malignancies

Introduction: The use of antiangiogenic strategy in the treatment of advanced colorectal cancers has been largely evidence-based. More recently, novel vascular endothelial growth factor receptor (VEGFR) inhibitors have been studied in other gastrointestinal diseases. Ramucirumab, a recombinant monoclonal antibody that binds to VEGFR2 extracellular domain with a much greater affinity compared to its natural ligand, showed second-line effectiveness for patients with gastric or colorectal carcinomas.

Areas covered: We perform a narrative literature review. The aims of our work are to recall the current evidence of its efficacy in the treatment of gastric, hepatocellular and colorectal cancers and to present the ongoing studies enrolling gastrointestinal cancer patients in which ramucirumab is being tested.

Expert commentary: The landscape of angiogenesis-inhibition for the treatment of GI malignancies is rapidly evolving. The results of the REGARD and RAINBOW trials renewed the interest for antiangiogenic agents in gastric cancer and determined a swift change in the treating paradigm for this disease. Accordingly, ramucirumab was shown to be effective in pretreated colorectal cancer patients and it is being tested in other gastrointestinal malignancies.     

Novel platinum agents and mesenchymal stromal cells for thoracic malignancies: state of the art and future perspectives

ABSTRACT

Introduction: Non-small cell lung cancer and malignant pleural mesothelioma represent two of the most intriguing and scrutinized thoracic malignancies, presenting interesting perspectives of experimental development and clinical applications.

Areas covered: In advanced non-small cell lung cancer, molecular targeted therapy is the standard first-line treatment for patients with identified driver mutations; on the other hand, chemotherapy is the standard treatment for patients without EGFR mutations or ALK rearrangement or those with unknown mutation status. Once considered an ineffective therapy in pulmonary neoplasms, immunotherapy has been now established as one of the most promising therapeutic options.

Mesenchymal stromal cells are able to migrate specifically toward solid neoplasms and their metastatic localizations when injected intravenously. This peculiar cancer tropism has opened up an emerging field to use them as vectors to deliver antineoplastic drugs for targeted therapies.

Expert opinion: Molecular targeted therapy and immunotherapy are the new alternatives to standard chemotherapy. Mesenchymal stromal cells are a new promising tool in oncology and—although not yet utilized in the clinical practice, we think they will represent another main tool for cancer therapy and will probably play a leading role in the field of nanovectors and molecular medicine.     

Perspectives of HER2-targeting in gastric and esophageal cancer

Introduction: The blockade of HER2 signaling has significantly improved the outlook for esophagogastric cancer patients. However, targeting HER2 still remains challenging due to complex biology of this receptor in gastric and esophageal cancers.

Areas covered: Here, we review complex HER2 biology, current methods of HER2 testing and tumor heterogeneity of gastroesophageal cancer. Ongoing and completed clinical research data are discussed.

Expert opinion: HER2 overexpression is a validated target in gastroesophageal cancer, with therapeutic implications resulting in prolonged survival when inhibited in the front-line setting. With standardized HER2 testing in gastro-esophageal cancer, the ongoing trials are testing newer agents and combinations including combination of anti-HER2 antibodies with immunotherapy. Clonal heterogeneity and emergence of resistance will challenge our approach to treating these patients beyond the frontline settings.     

Emerging treatment for ALK-positive lung cancer

Introduction: Lung cancer is associated with poor prognosis and limited benefit from chemotherapy. The treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the discovery of targetable genetic alterations, including the ALK fusion oncogene.

Areas covered: Three drugs have been approved for clinical use in ALK-positive patients – crizotinib, ceritinib and alectinib. Unfortunately, treatment resistance inevitably develops. Several mechanisms of acquired resistance are reported. In this review, we will discuss emerging treatment options in ALK-positive advanced NSCLC and strategies to overcome resistance mechanisms, including newer generation of ALK inhibitors, Hsp90 inhibitors and immunotherapy.

Expert opinion: Tremendous advances have been made in the treatment of ALK-positive lung cancers, but management hurdles still exist, including universal development of resistance to ALK inhibitors and limited CNS activity. Given that specific treatment strategies target distinct patterns of resistance, re-biopsy at the time of progression appears necessary to optimize management. However, there remain many issues in routine clinical application including the burden placed on the patients by serial biopsies and the risks of repeat invasive procedures. Future studies are needed to validate the usage of non- or minimally invasive tests and to determine the optimal orders of utilizing different ALK inhibitors.     

The potential of neurotrophic tyrosine kinase (NTRK) inhibitors for treating lung cancer

Introduction: Molecular alterations in neurotrophic tyrosine kinase (NTRK) genes have been identified in several solid tumors including lung cancer. Pre-clinical and clinical evidence suggested their potential role as oncogenic drivers and predictive biomarkers for targeted inhibition, leading to the clinical development of a new class of compounds blocking the NTRK molecular pathway, which are currently undner early clinical investigation.

Area covered: This review describes the biology of the NTRK pathway and its molecular alterations in lung cancer. It focuses on the pre-clinical and clinical development of emerging NTRK inhibitors, which have shown very promising activity in early phase I studies.

Expert opinion: Among the several NTRK-inhibitors, entrectinib and LOXO-101 are those in more advanced stage of clinical development. Both agents have shown encouraging activity along with a tolerable safety profile in patients with different solid tumors harboring NTRK-fusions, emerging as new promising therapeutic options for molecularly selected patients with advanced Trk-driven lung cancers. Results from ongoing phase II basket trials are eagerly awaited.     

Anti-angiogenic drugs currently in Phase II clinical trials for gynecological cancer treatment

Introduction: Numerous female patients suffer from gynecological cancers every year. When it comes to recurrent or chemoresistant cancers, there are limited treatment options. For decades, much enthusiasm has been shown for novel therapeutic strategies for cancers, and anti-angiogenesis agents appear to be a potential option. Since several promising angiogenesis inhibitors for certain cancers have been approved by Food and Drug Administration, more and more anti-angiogenic drugs are put into clinical trials.

Areas covered: In this review, the anti-angiogenic agents in Phase II clinical trials for gynecological cancer treatment are highlighted. This review mainly focuses on 5-year reports on angiogenesis inhibitors concerning ovarian cancer, cervical cancer, uterine leiomysarcoma and endometrial cancer. Inhibitors reviewed in this paper include bevacizumab, volociximab, aflibercept, temsirolimus, enzastaurin, trebananib, sunitinib, imatinib, pazopanib, sorafenib and nintedanib.

Expert opinion: These anti-angiogenic drugs while used either alone or in combination with chemotherapy, presented mixed results in treating gynecological cancers. The real challenge is how to take best advantage of the anti-angiogenesis hypothesis for therapeutic benefit. Much remains to be done before these molecules work efficaciously in treating gynecological cancer.     

Cytokines for the treatment of gastrointestinal cancers: clinical experience and new perspectives

Introduction: Cytokines are key mediators of the immune system and have been proposed as therapeutic agents against cancer, either as recombinant proteins, or as transgenes in gene therapy approaches. Stimulation of immune responses against cancer cells is an appealing method to treat tumors with high risk of relapse and systemic dissemination.

Areas covered: We provide a critical overview of clinical trials involving the use of cytokines for the treatment of liver, colon and pancreatic cancers. Special attention has been paid to advances in the field of gene therapy and oncolytic viruses. The potential of new developments still in a pre-clinical stage is also discussed. We have revised public sources of information (PubMed, US National Institutes of Health clinical trials database) up to January 2013.

Expert opinion: The complexity of the immune system and the unfavorable pharmacokinetic properties of cytokines limit the efficacy of these molecules as single agents for the treatment of cancer. Expression from gene therapy vectors, together with new methods of targeting and stabilization, may overcome these hurdles. We believe cytokines will play a crucial role as part of combined approaches, enhancing the action of adoptive cell immunotherapy, oncolytic viruses or biological therapies.     

Current and future treatment options for esophageal cancer in the elderly

Introduction: Esophageal cancer is the eighth most common cancer globally and has the sixth worst prognosis because of its aggressiveness and poor survival. Data regarding cancer treatment in older patients is limited because the elderly have been under-represented in clinical trials. Therefore, we reviewed the existing literature regarding treatment results for elderly patients (70+ years).

Areas covered: We used pubmed to analyze the actual literature according to elderly esophageal cancer patients with subheading of incidence, esophagectomy, chemoradiation or chemotherapy. The main points of interest were treatment options for patients with Barrett’s esophagus or early carcinoma, advanced tumor stages, and inoperable cancer.

Expert opinion: The incidence of esophageal cancer has been increasing over the past thirty years, with a rapid increase of esophageal adenocarcinoma in Western industrialized nations. Patients aged over 60 years have been particularly affected. In this review, we have shown that elderly patients with esophageal cancer have various alternatives for adequate treatment. Clinical evaluation of comorbidity is necessary to make treatment decisions. Therapeutic options for early carcinomas are endoscopic or surgical resection. For elderly patients with advanced carcinomas, preoperative chemoradiation or chemotherapy should be discussed.     

Safety of palliative chemotherapy in advanced pancreatic cancer

ABSTRACT

Introduction: Pancreatic cancer is a major health burden. Currently, the majority of patients is diagnosed at advanced stages and thus qualifies for palliative chemotherapy. Gemcitabine monotherapy has been the gold standard for many years. Recently, more effective chemotherapeutic regimens have shown meaningful clinical activity in patients with metastatic pancreatic cancer.

Areas covered: In this review we have aimed to give an overview on the treatment options for patients diagnosed with metastatic pancreatic cancer with an emphasis on the safety and toxicity of the applied regimens. We have conducted a pubmed search using the terms ‘metastatic pancreatic cancer’, ‘palliative chemotherapy’, ‘safety’ and ‘toxicity’. Our special focus rested on randomized phase III trials to provide readers with the highest level of available evidence.

Expert opinion: The emergence of new and more effective chemotherapy regimens gives clinicians more freedom in the treatment of metastatic pancreatic cancer. While being more effective, these regiments have a considerable degree of toxicity. Choosing the right treatment for any individual will be the next major challenge treating patients with pancreatic cancer.     

The hedgehog pathway inhibitor GDC-0449 shows potential in skin and other cancers

Background: The hedgehog signalling pathway is vital in early development, but then becomes dormant, except in some cancer tumours. Hedgehog inhibitors are being developed for potential use in cancer.

Objectives/methods: The objective of this evaluation is to review the initial clinical studies of the hedgehog inhibitor, GDC-0449, in subjects with cancer.

Results: Phase I trials have shown that GDC-0449 has benefits in subjects with metastatic or locally advanced basal-cell carcinoma and in one subject with medulloblastoma. GDC-0449 was well tolerated.

Conclusions: Long-term efficacy and safety studies of GDC-0449 in these conditions and other solid cancers are now underway. These clinical trials with GDC-0449, and trials with other hedgehog inhibitors, will reveal whether it is beneficial and safe to inhibit the hedgehog pathway in a wide range of solid tumours or not.     

Developmental DNA methyltransferase inhibitors in the treatment of gynecologic cancers

Introduction: DNA methylation has become an attractive target for the treatment of cancer. DNA methyltransferase inhibitors have proven useful for the treatment of myelodysplastic syndrome and are being evaluated in gynecological neoplasias.

Areas covered: We provide an overview of the current knowledge on DNA methylation and cancer and the role of DNA methylation in cervical, ovarian and endometrial carcinomas. The results of recent clinical trials with demethylating agents for cervical and ovarian cancer treatment are also discussed.

Expert opinion: There are few studies of DNA demethylating agents for cervical and ovarian cancer treatment; nevertheless, the results are promising. To accelerate these advances, there are at least two actions that can be simultaneously pursued. One is to greatly increase the number of small clinical exploratory trials with existing demethylating drugs and using methylome analyses to identify predictive factors for response and/or toxicity. The second is finding out epigenetic ‘drivers’ unique to gynecological cancers and their subtypes, and then proceed to clinical trials in a highly selected population of patients. It is expected that in the future, DNA demethylation could have a role in the treatment of gynecologic cancers.     

AEZS-108: a targeted cytotoxic analog of LHRH for the treatment of cancers positive for LHRH receptors

Introduction: Receptors for the luteinizing hormone-releasing hormone [LHRH, also known as gonadotropin-releasing hormone (GnRH)] can be regarded as an ideal target for a personalized medicine approach in cancer therapy. LHRH receptors are expressed in about 80% of human endometrial and ovarian cancers, 86% of prostate cancer, and about 50% of breast cancers including triple-negative breast cancer, as well as bladder, colorectal, and pancreatic cancers, sarcomas, lymphomas, melanomas, and renal cell carcinomas. Apart from the pituitary and reproductive organs, other organs and hematopoietic stem cells express LHRH receptors. Thus, a targeted cytotoxic LHRH analog such as AEZS-108 (formerly known as AN-152), in which doxorubin is linked to the LHRH agonist [D-Lys⁶]LHRH, appears to be a suitable drug for targeted chemotherapy of cancers expressing receptors for LHRH, which would be more efficacious and less toxic than standard systemic chemotherapy.

Areas covered: This review discusses the development of AEZS-108, its targeting mechanism, preclinical studies, and clinical trials in patients with endometrial, ovarian, prostatic, and bladder cancers. We emphasize its development as a personalized medicine approach. The studies reviewed demonstrate the effects of the cytotoxic LHRH analog, AEZS-108, mediated by LHRH receptors, in in vivo models of LHRH-receptor-positive human endometrial, ovarian, breast, prostatic, colorectal, pancreatic, and bladder cancers xenografted into nude mice. Intravenous administration of AEZS 108 inhibits the growth of LHRH-receptor-positive tumors better than equimolar doses of the cytotoxic agent doxorubicin and is far less toxic. AEZS 108 has no antitumor activity in cancers negative to LHRH receptor. This strongly supports the concept of targeting cytotoxic chemotherapy to tumor cells expressing LHRH receptors. Early clinical trials have demonstrated the efficacy of AEZS-108. A Phase I trial assessed the maximum tolerated dose and pharmacokinetics and pharmacodynamics of AEZS-108 given once every 3 weeks in patients with gynecological cancers. Two Phase II studies in heavily pretreated ovarian and recurrent endometrial cancers showed good clinical activity after a maximum of six courses of AEZS-108 as a single agent. Ongoing clinical studies with AEZS-108 in men with castration-resistant prostate cancer and patients with chemotherapy refractory bladder cancer had shown early signs of clinical efficacy. Side effects are moderate and easily manageable. In particular, no pituitary or cardiac toxicity is observed.

Expert opinion: AEZS-108 is a cytotoxic analog designed for receptor-mediated targeted chemotherapy and consists of an LHRH carrier linked to doxorubicin. Preclinical studies demonstrate that the uptake of AEZS-108 is achieved by receptor-mediated endocytosis. Results of Phase I and II clinical trials in patients with gynecological cancers demonstrated anticancer activity without cardiotoxicity even in highly pretreated patients. Phase I/II studies in castration-resistant prostate cancer and chemotherapy refractory bladder cancer are in progress. Targeted chemotherapy with a cytotoxic analog of LHRH, such as AEZS-108, is therefore being considered for Phase III studies in advanced endometrial cancers positive for LHRH receptor. LHRH receptors are also present in human colon cancers, melanomas, lymphomas, and sarcomas, and treatment of these cancers with AEZS-108 should also be undertaken. Before such treatment with AEZS-108 is begun, the status of tumoral LHRH receptors of patients must be determined.     

Development of an orphanin FQ (OFQ) receptor antagonist for the treatment of chronic pain

Introduction: Hedgehog (Hh) signaling pathway plays key roles in embryonic development, formation and maintenance of cancer stem cells (CSCs) and acquisition of epithelial-to-mesenchymal transition (EMT). Since CSCs and EMT are important biological factors responsible for cancer cell invasion, metastasis, drug resistance and tumor recurrence, the Hh signaling pathway is believed to be an important target for cancer therapy.

Areas covered: In recent years, small-molecule inhibitors of Hh signaling have been synthesized for cancer treatment. Clinical trials using these inhibitors are being conducted to determine their toxicity profiles and efficacies. In addition, nutraceuticals (such as isoflavones, curcumin, vitamin D, etc) have been shown to inhibit cancer growth through downregulation of Hh signaling.

Expert opinion: Inhibition of Hh signaling is important for suppression of cancer growth, invasion, metastasis and recurrence in cancer therapy. However, targeting only one molecule in Hh signaling may not be sufficient to kill cancer cells because cancers show deregulation of multiple signals. Therefore, utilizing new technologies to determine alterations in Hh and other signals for individuals and designing combination strategies with small-molecule Hh inhibitors, nutraceuticals and other chemotherapeutics in targeted personalized therapy could have a significant effect on improving the overall survival of patients with cancers.     

Emerging therapeutics in refractory renal cell carcinoma

Introduction: Metastatic renal cell carcinoma (mRCC) has seen the introduction of numerous new treatments over the past decade. However, the efficacy of these therapies has plateaued, and new treatment options are needed for the majority of patients with mRCC whose disease inevitably progresses through one or more standard therapies (‘refractory’ mRCC). Recently approved agents in this space have shown great promise.

Areas covered: This article reviews the evidence behind current management strategies for mRCC. After reviewing clinical trials that established current first-line therapies and agents used in the refractory setting, we address new ideas for the treatment of refractory disease including combination therapies and novel targeted agents. In particular, we focus on targeted immunotherapy in refractory mRCC. We conclude by considering future directions in combination treatments utilizing these novel agents.

Expert opinion: Numerous approaches have produced tangible benefits for the treatment of patients with mRCC. These include development of next generation VEGFR/TKIs, targeted immunotherapy agents, and the development of combined regimens. In particular, immunotherapy agents targeting the PD1/PD-L1 pathway have shown great promise with a robust survival advantage seen in patients treated with nivolumab. A tolerable side effect profile of immunotherapy agents makes them amenable for use in combination therapies and ongoing trials are addressing this question.     

The PD-1 pathway as a therapeutic target to overcome immune escape mechanisms in cancer

Introduction: Immunotherapy is emerging as a powerful approach in cancer treatment. Preclinical data predicted the antineoplastic effects seen in clinical trials of programmed death-1 (PD-1) pathway inhibitors, as well as their observed toxicities. The results of early clinical trials are extraordinarily promising in several cancer types and have shaped the direction of ongoing and future studies.

Areas covered: This review describes the biological rationale for targeting the PD-1 pathway with monoclonal antibodies for the treatment of cancer as a context for examining the results of early clinical trials. It also surveys the landscape of ongoing clinical trials and discusses their anticipated strengths and limitations.

Expert opinion: PD-1 pathway inhibition represents a new frontier in cancer immunotherapy, which shows clear evidence of activity in various tumor types including NSCLC and melanoma. Ongoing and upcoming trials will examine optimal combinations of these agents, which should further define their role across tumor types. Current limitations include the absence of a reliable companion diagnostic to predict likely responders, as well as lack of data in early-stage cancer when treatment has the potential to increase cure rates.     

Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer

Introduction: Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer.

Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications.

Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.