Efficacy, patterns of use and cost of Pertuzumab in the treatment of HER2+ metastatic breast cancer in Singapore: The National Cancer Centre Singapore experience

BACKGROUND Pertuzumab is a humanized anti-human epidermal growth factor receptor 2(HER2)monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer(MBC)when used in combination with a taxane and Trastuzumab,and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast cancer.There are currently few reports on the pattern of use and value of Pertuzumab in real world settings.Our study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian population.AIM To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in Singapore.METHODS A retrospective study of 304 HER2-positive MBC patients seen at National Cancer Centre Singapore between 2011-2017 was conducted.Demographic and clinical data were extracted from electronic medical records.Clinical characteristics and billing data of patients who received Pertuzumab were compared with those who did not.RESULTS Thirty-one(62.0%)of the fifty(16.4%)patients who received Pertuzumab as firstline therapy.With a median follow-up of 21.5 mo,there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups[51.5(95%CI:35.8–60.0)vs 32.9(95%CI:28.1–37.5)mo;P=0.0128].Two(4.88%)patients in the Pertuzumab group experienced grade 3(G3)cardiotoxicity.The median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab group.The median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.CONCLUSION This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardiotoxicity.However,the proportionate cost of Pertuzumab therapy remains high and further cost-effectiveness studies should be conducted.

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis

In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.

A randomized controlled trial of Promoting Physical Activity in Regional and Remote Cancer Survivors(PPARCS)

Background:Physical activity(PA)is important for cancer survivors.Trials of remotely delivered interventions are needed to assist in reaching under-served non-metropolitan cancer survivors.The objective of this study was to ascertain whether wearable technology,coupled with health coaching was effective in increasing PA in breast and colorectal cancer survivors living in regional and remote areas in Australia.Methods:Cancer survivors from 5 states were randomized to intervention and control arms.Intervention participants were given a Fitbit Charge 2TMand received up to 6 telephone health coaching sessions.Control participants received PA print materials.Accelerometer assessments at baseline and 12 weeks measured moderate-to-vigorous PA(MVPA),light PA,and sedentary behavior.Results:Eighty-seven participants were recruited(age=63±11 years;74(85%)female).There was a significant net improvement in MVPA of 49.8 min/week,favoring the intervention group(95%confidence interval(95%CI):13.6-86.1,p=0.007).There was also a net increase in MVPA bouts of 39.5 min/week(95%CI:11.9-67.1,p=0.005),favoring the intervention group.Both groups improved light PA and sedentary behavior,but there were no between-group differences.Conclusion:This’s the first study to demonstrate that,when compared to standard practice(i.e.,PA education),a wearable technology intervention coupled with distance-based health coaching,improves MVPA in non-metropolitan cancer survivors.The results display promise for the use of scalable interventions using smart wearable technology in conjunction with phone-based health coaching to foster increased PA in geographically disadvantaged cancer survivors.

Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer:A systematic review

BACKGROUND Colorectal cancer(CRC)is the third most frequent and the second most fatal cancer.The search for more effective drugs to treat this disease is ongoing.A better understanding of the mechanisms of CRC development and progression may reveal new therapeutic strategies.Ubiquitin-specific peptidases(USPs),the largest group of the deubiquitinase protein family,have long been implicated in various cancers.There have been numerous studies on the role of USPs in CRC;however,a comprehensive view of this role is lacking.AIM To provide a systematic review of the studies investigating the roles and functions of USPs in CRC.METHODS We systematically queried the MEDLINE(via PubMed),Scopus,and Web of Science databases.RESULTS Our study highlights the pivotal role of various USPs in several processes implicated in CRC:Regulation of the cell cycle,apoptosis,cancer stemness,epithelial–mesenchymal transition,metastasis,DNA repair,and drug resistance.The findings of this study suggest that USPs have great potential as drug targets and noninvasive biomarkers in CRC.The dysregulation of USPs in CRC contributes to drug resistance through multiple mechanisms.CONCLUSION Targeting specific USPs involved in drug resistance pathways could provide a novel therapeutic strategy for overcoming resistance to current treatment regimens in CRC.

Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy

The advent of single-cell RNA sequencing(scRNA-seq)has provided insight into the tumour immune microenvironment(TIME).This review focuses on the application of scRNA-seq in investigation of the TIME.Over time,scRNA-seq methods have evolved,and components of the TIME have been deciphered with high resolution.In this review,we first introduced the principle of scRNA-seq and compared different sequencing approaches.Novel cell types in the TIME,a continuous transitional state,and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer.Thus,we concluded novel cell clusters of cancerassociated fibroblasts(CAFs),T cells,tumour-associated macrophages(TAMs)and dendritic cells(DCs)discovered after the application of scRNA-seq in TIME.We also proposed the development of TAMs and exhausted T cells,as well as the possible targets to interrupt the process.In addition,the therapeutic interventions based on cellular interactions in TIME were also summarized.For decades,quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer.Summarizing the current findings,we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy,which can subsequently be implemented in the clinic.Finally,we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.

Prescription of Cancer Treatment Modalities in Developing Countries:Results from a Multi-Centre Observational Study

Background: Treatment is an important component of a comprehensive cancer control approach and its outcomes strongly depend on infrastructure, equipment, human and financial resources available. Therefore it is imperative to generate evidence-based tools to assist health policy makers from low resourced countries in planning efficient and equitable treatment services for a defined population based on what it is feasible to these settings. Methods: The intended cancer spe-cific treatment planned and written in the patients’ medical record (treatment prescription) of untreated adult cancer cases (≥18 years of age), excluding non-melanoma skin cancer, was recorded in a chronological way from 1 January 2012 onwards in a group of eight comprehensive cancer centres located in middle income countries and offering the main modalities of cancer treatment (surgery, medical oncology and radiotherapy). Results: A total of 17,713 medical records were reviewed, of which 7106 (54.2%) met the eligibility criteria. Prescription of main cancer treatment modalities were distributed as follows: 57.6% for chemotherapy (n = 4093), 56.8% for surgery (n = 4038), and 46.8% for radiotherapy (n = 3327). There was a predominance of plans consisting of combined treatment modalities over monotherapy (55.2% versus 44.8%). At the time of diagnosis 54.3% of the cancer cases had disease that had spread beyond the primary site, 41.2% were considered as having local disease and in 4.5% of the cases the information on disease extension was unknown. Conclusions: The results obtained should be seen as an approximation of cancer treatment service demand based on what it is currently practiced and therefore feasible in developing countries, particularly in middle income countries.

Prevention of thromboembolic events after radical prostatectomy in patients with hereditary thrombophilia due to a factor V Leiden mutation by multidisciplinary coagulation management

Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia.The increased risk of thromboembolic events is three-to seven-fold in heterozygous and to 80-fold in homozygous patients.Methods:Within our prospectively collected database,we analysed 33006 prostate cancer patients treated with RP between December 2001 and December 2020.Of those,patients with factor V Leiden mutation were identified.All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation.Thromboembolic complications(deep vein thrombosis and pulmonary embolism)were assessed during hospital stay,as well as according to patient reported outcomes within the first 3 months after RP.Results:Overall,85(0.3%)patients with known factor V Leiden mutation were identified.Median age was 65(interquartile range:61-68)years.There was at least one thrombosis in 53(62.4%)patients and 31(36.5%)patients had at least one embolic event in their medical history before RP.Within all 85 patients with factor V Leiden mutation,we experienced no thromboembolic complications within the first 3 months after surgery.Conclusion:In our cohort of patients with factor V Leiden mutation,no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept.This may reassure patients with this hereditary condition who are counselled for RP.

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

奈妥匹坦帕洛诺司琼预防化疗引起的恶心呕吐:从临床试验到日常临床实践

化疗引起的恶心呕吐(CINV)是众多抗癌药物治疗中常见的不良事件,不仅会对患者生活质量带来负面影响,还有可能影响化疗效果。目前,指南建议的止吐方案可以预防大部分癌症患者的CINV。但临床医师并不能始终遵循指南建议,患者也常常难以坚持医师处方的治疗。因此需要采取一些提高指南依从性的方法。奈妥匹坦帕洛诺司琼(NEPA)是首个也是唯一一个固定剂量复方止吐药,由奈妥匹坦(口服)/福奈妥匹坦(静脉给药)与帕洛诺司琼(PALO)组成。NEPA可以联合地塞米松组成三联止吐方案,这是用于高致吐性化疗(HEC)患者和部分中致吐性化疗(MEC)患者预防CINV的推荐方案。因此,NEPA止吐治疗操作简单便捷,可能有助于提高指南依从性。本综述对CINV进行了概括,评价了在临床试验和真实实践中积累的NEPA止吐效果及安全性方面的证据,同时也评价了在关键临床试验之外的环境下,即日常临床环境中使用NEPA进行止吐的初步证据。此外,本文还评述了化疗期间使用NEPA控制恶心症状和提高患者生活质量,这是癌症患者管理中面临的两个大挑战。

Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

The PI3K/Akt/m TOR pathway in ovarian cancer: therapeutic opportunities and challenges

The phosphatidylinositol 3 kinase(PI3K) pathway is frequently altered in cancer, including ovarian cancer(OC). Unfortunately, despite a sound biological rationale and encouraging activity in preclinical models, trials of first-generation inhibitors of mammalian target of rapamycin(m TOR) in OC have demonstrated negative results. The lack of patient selection as well as resistance to selective m TOR complex-1(m TORC1) inhibitors could explain the disappointing results thus far. Nonetheless, a number of novel agents are being investigated, including dual m TORC1/m TORC2, Akt, and PI3 K inhibitors. Although it is likely that inhibition of the PI3K/Akt/m TOR pathway may have little effect in unselected OC patients, certain histological types, such as clear cell or endometrioid OC with frequent phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit alpha(PIK3CA) and/or phosphatase and tensin homolog(PTEN) alterations, may be particularly suited to this approach. Given the complexity and redundancy of the PI3 K signaling network, PI3 K pathway inhibition may be most useful in combination with either chemotherapy or other targeted therapies, such as MEK inhibitors, anti-angiogenic therapy, and hormonal therapy, in appropriately selected OC patients. Here, we discuss the relevance of the PI3 K pathway in OC and provide an up-to-date review of clinical trials of novel PI3 K inhibitors alone or in combination with cytotoxics and novel therapies in OC. In addition, the challenges of drug resistance and predictive biomarkers are addressed.

Is nasopharyngeal cancer really a “Cantonese cancer”?

Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage.However,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese cancer.We searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of NPC.The migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical accounts.Genetic and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common ancestry.Genetic studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern Bai-Yue.All these populations have a high incidence of NPC.Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.

The VEGF signaling pathway in cancer: the road ahead

The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.

Regional but fatal: Intraperitoneal metastasis in gastric cancer

Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.

MicroRNAs:Promising chemoresistance biomarkers in gastric cancer with diagnostic and therapeutic potential

Gastric cancer(GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stage disease. However,response to chemotherapy varies widely,with some patients presenting no or only minor response to treatment. Hence,chemotherapy resistance is a major clinical problem that impacts on outcome. Unfortunately,to date there are no reliable biomarkers available that predict response to chemotherapy before the start of the treatment,or that allow modification of chemotherapy resistance. MicroRNAs(miRNAs) could provide an answer to this problem. miRNAs are involved in the initiation and progression of a variety of cancer types,and there is evidence that miRNAs impact on resistance towards chemotherapeutic drugs as well. This current review aims to provide an overview about the potential clinical applicability of miRNAs as biomarkers for chemoresistance in GC.The authors focus in this context on the potential of miRNAs to predict sensitivity towards different chemotherapeutics,and on the potential of miRNAs to modulate sensitivity and resistance towards chemotherapy in GC.

Current role of minimally invasive approaches in the treatment of early gastric cancer

Despite declining incidence,gastric cancer remains one of the most common cancers worldwide.Early detection in population-based screening programs has increased the number of cases of early gastric cancer,representing approximately 50%of newly detected gastric cancer cases in Asian countries.Endoscopic mucosal resection and endoscopic submucosal dissection have become the preferred therapeutic techniques in Japan and Korea for the treatment of early gastric cancer patients with a very low risk of lymph node metastasis.Laparoscopic and robotic resections for early gastric cancer,including function-preserving resections,have propagated through advances in technology and surgeon experience.The aim of this paper is to discuss the recent advances in minimally invasive approaches in the treatment of early gastric cancer.

Capecitabine with radiation is an effective adjuvant therapy in gastric cancers

AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers.RESULTS:A total of 108 patients were reviewed.Median age at diagnosis was 60.The majority of the patients(64.8%) had advanced stage Ⅲ and Ⅳ disease(with no distant metastasis).All except 4 patients had D2 gastrectomy.Twenty one patients(19.4%) had positive surgical resection margins.Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone.For the patients in the chemotherapy-only group,all had fluoropyrimidine-based therapy,with added cisplatin in 7 patients and epirubicin in 2 patients.Median recurrence-free survival was longer for the XRT group(52 mo) compared to the 5FU-RT(35 mo) and chemotherapy-only groups(25 mo)(P=0.48).The patients in the XRT group achieved similar median overall survival(53 mo) as the 5FU-RT(54 mo) and the chemotherapy-only groups(44 mo)(P=0.5).CONCLUSION:Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers.

Hereditary diffuse gastric cancer: What the clinician should know

Hereditary diffuse gastric cancer(HDGC) is an inherited autosomal dominant syndrome with a penetrance of up to 80% affecting diverse geographic populations. While it has been shown to be caused mainly by germline alterations in the E-cadherin gene(CDH1), problematically, the genetic diagnosis remains unknown in up to 60% of patients. Given the important knowledge gaps regarding the syndrome, asymptomatic carriers of CDH1 mutations are advised for a prophylactic total gastrectomy. Intensive annual endoscopic surveillance is the alternative for carriers who decline gastrectomy. As HDGCs have a prolonged indolent phase, this provides a window of opportunity for surveillance and treatment. Recent findings of other gene defects in CTNNA1 and MAP3K6, as well as further characterization of CDH1 mutations and their pathogenicity will change the way HDGC patients are counselled for screening, surveillance and treatment. This review will bring the reader up to date with these changes and discuss future directions for research; namely more accurate risk stratification and surveillance methods to improve clinical care of HDGC patients.

Management of recurrent rectal cancer:A population based study in greater Amsterdam

AIM: To analyze,retrospectively in a population-based study,the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision (TME). METHODS: All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection (632 patients) were selected from the Amsterdam Cancer Registry. For patients with recurrent disease,information on treatment of the recurrence was collected from the medical records. RESULTS: Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients (10%). Thirty-two patients had an isolated local recurrence. Ten of these 32 patients (31%) underwent radical re-resection and experienced the highest survival (three quarters survived for at least 3 years). Eight patients (25%) underwent non-radical surgery (median survival 24 mo),seven patients (22%) were treated with radio-and/or chemotherapy without surgery (median survival 15 mo) and seven patients (22%) only received best supportive care (median survival 5 mo). Distant dissemination occurred in 124 patients (20%) of whom 30 patients also had a local recurrence. The majority (54%) of these patients were treated with radio-and/or chemotherapy without surgery (median survival 15 mo). Twenty-seven percent of these patients only received best supportive care (median survival 6 mo),while 16% underwent surgery for their recurrence. Survival was best in the latter group (median survival 32 mo). CONCLUSION: Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME,patients can benefit from additional treatment,especially if a radical resection is feasible.

Premalignant lesions and gastric cancer: Current understanding

Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In this review we reflect upon the historic approaches to describing premalignant lesions and GC,highlight the current molecular landscape and how this could inform future risk assessment prevention strategies.