Predictive Markers For Immunotherapy Research Articles

Abstract 7040: Mutations in cytoskeleton genes SPTAN1/SPTBN1 serve as novel predictive markers for immunotherapy against bladder cancer

Abstract Cancer progression is often driven by somatic mutations. Despite several well-known driver mutations, more evidence has shown that genetic alterations in cytoskeleton organization enhance tumor aggressiveness and promote cancer progression, suggesting their roles as potential drivers. In this study, pan-cancer genetic analyses by using TCGA cohorts, more frequent mutation events were found in cytoskeleton-related genes as compared to total annotated genes, especially in cancers derived from hollow organs. High-dimensional analysis of molecular alterations in cancer (HD-MAC) suggested gene mutations in SPTAN1 and its partner SPTBN1 as potential prognostic biomarkers for clinical outcomes of patients with bladder cancer. Gene knockdown in either SPTAN1 or SPTBN1, mimicking silencing mutations in cancer tissues, caused cell morphology changes, DNA breaks, and alternations in cytokine profiles via activating cGAS-STING mediated interferon signaling. Xenograft tumor models also indicate accelerated tumor growth in SPTAN1- or SPTBN1-silenced cells, suggesting a more advanced cancer type. Based on immune staining in both human and mouse samples, increased CD8+ T cell infiltration was in tumor lesions with mutations or truncations in SPTAN1/SPTBN1 genes. In addition, several known substitution mutations were found as potent neo-antigens based on MHC II binding prediction, which could be utilized as targets for immune checkpoint therapy. This study provides a novel insight into how the cytoskeleton can contribute to cancer progression and find out predictive biological indicators with therapeutic values. Citation Format: Brian Yu-Ting Kuo. Mutations in cytoskeleton genes SPTAN1/SPTBN1 serve as novel predictive markers for immunotherapy against bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7040.

Prognostic and Predictive Markers for Immunotherapy in Non Small Cell Lung Cancer

n the last decade, lung cancer patients have benefited from novel and efficient therapies such as immunotherapy. However, currently, there is no standardized method for predicting the success of immunotherapy. We review the potential immune markers such as the tumor mutational burden (TMB), the presence of intratumor infiltrating lymphocytes (TIL), the neutrophils/ lymphocytes ratio (NLR) and microsatellite instability (MSI), providing a summary of their reported utility, prognostic and predictive value.

Homogenous TP53mut-associated tumor biology across mutation and cancer types revealed by transcriptome analysis

TP53 is the most frequently mutated gene in human cancer. While no TP53-targeting drugs have been approved in the USA or Europe so far, preclinical and clinical studies are underway to investigate targeting of specific or all TP53 mutations, for example, by restoration of the functionality of mutated TP53 (TP53mut) or protecting wildtype TP53 (TP53wt) from negative regulation. We performed a comprehensive mRNA expression analysis in 24 cancer types of TCGA to extract (i) a consensus expression signature shared across TP53 mutation types and cancer types, (ii) differential gene expression patterns between tumors harboring different TP53 mutation types such as loss of function, gain of function or dominant-negative mutations, and (iii) cancer-type-specific patterns of gene expression and immune infiltration. Analysis of mutational hotspots revealed both similarities across cancer types and cancer type-specific hotspots. Underlying ubiquitous and cancer type-specific mutational processes with the associated mutational signatures contributed to explaining this observation. Virtually no genes were differentially expressed between tumors harboring different TP53 mutation types, while hundreds of genes were over- and underexpressed in TP53mut compared to TP53wt tumors. A consensus list included 178 genes that were overexpressed and 32 genes that were underexpressed in the TP53mut tumors of at least 16 of the investigated 24 cancer types. In an association analysis of immune infiltration with TP53 mutations in 32 cancer subtypes, decreased immune infiltration was observed in six subtypes, increased infiltration in two subtypes, a mixed pattern of decreased and increased immune cell populations in four subtypes, while immune infiltration was not associated with TP53 status in 20 subtypes. The analysis of a large cohort of human tumors complements results from experimental studies and supports the view that TP53 mutations should be further evaluated as predictive markers for immunotherapy and targeted therapies.

Predictive markers of immunotherapy in cervical cancer

Study of PD-L1 expression in squamous and adenosquamous cell cervical cancer (CC) by immunohistochemical (IHC) method, assessment of the relationship between PD-L1 tumor status and its clinical and morphological characteristics, TILs, MSI/dMMR, and HPV tumor status. Surgical material was obtained from 41 patients with CC, on which the expression of PD-L1, proteins of the MMR system and p16 was studied by the IHC method, the TILs index was determined. Positive PD-L1 status was found in 51.2% of the studied CC samples. In the study sample, the level of PD-L1 expression depended on the severity of lymphoid infiltration of the tumor (p=0.038), it was shown that a positive PD-L1 status of CC can be expected with a TILs value greater than or equal to 50%. The age of the patients, the histological variant of the tumor, the pT and pN stage, the presence of lymphovascular invasion, and the HPV status did not statistically significantly affect the level of PD-L1 expression, however, there was an association between the PD-L1 status and the grade of CC malignancy (p=0.027). The presence of the MSI/dMMR phenomenon was detected in a small percentage of carcinomas (4.9%), the PD-L1 status of these tumors was determined as positive. A positive PD-L1 status is determined in a significant number of cases of CC, regardless of most of the studied clinical and morphological characteristics; there is a statistically significant relationship between PD-L1 expression and the degree of tumor differentiation and TILs. It has been shown that CC with the MSI/dMMR phenomenon is characterized by a positive PD-L1 status. The authors consider it necessary to study the expression of PD-L1 in patients with cervical carcinomas in order to determine the possibility of prescribing personalized therapy with immune checkpoint inhibitors.

Identification of CKS1B as a prognostic indicator and a predictive marker for immunotherapy in pancreatic cancer.

As a regulatory subunit of cyclin kinase, CKS1B promotes cancer development and is associated with poor prognosis in multiple cancer patients. However, the intrinsic role of CKS1B in pancreatic cancer remains elusive. In our research, CKS1B expression in pancreatic tumor tissue was higher than that in normal tissue by TCGA, Oncomine and CPTAC databases analysis. Similar result was verified in our center tissues by qRT-PCR. CKS1B expression was closely relevant to histologic grading, prognosis, and TMB. GSEA showed that CKS1B mainly participated in the regulation of autophagy and T cell receptor signaling pathway. Furthermore, CIBERSORT analysis showed that there was a strong correlation between CKS1B expression and tumor immune cells infiltration. Drug sensitivity analysis showed that patients with high CKS1B expression appeared to be more sensitive to gemcitabine, 5-fluorouracil, and paclitaxel. We then investigated cell viability and migratory ability by CCK8 and transwell assay, respectively. Results indicated that CKS1B knockdown by short hairpin RNA significantly reduced pancreatic cancer cell viability and invasion via regulating PD-L1 expression. In conclusion, our research further demonstrates the role of CKS1B in pancreatic cancer and the signaling pathways involved. The association of CKS1B with immune infiltration and immune checkpoint may provide a new direction for immunotherapy of pancreatic cancer.

Association of microsatellite instability (MSI) status with the 5-year outcome and genetic ancestry in a large Brazilian cohort of colorectal cancer.

Colorectal cancer (CRC) has a high incidence and mortality worldwide. Microsatellite instability (MSI) is crucial in CRC, with distinct molecular and clinicopathological features in patients. Nowadays, it is a predictive marker for immunotherapy. We proposed to evaluate the 5-year outcome of MSI status in 1002 Brazilian CRC, and associate it with genetic ancestry, molecular and clinicopathological features. MSI evaluation was performed using molecular markers. MSI+ tumors were analyzed for alterations in 23 MSI-targeted genes. Genetic ancestry was evaluated using an Ancestry-Informative markers panel. MSI status was analyzed in relation to CRC specific survival and other clinical and genetic variables. MSI+ status was observed in 10.5% of cases. MSI+ status was significantly associated with the anatomic site right colon, mucinous histological type, clinical stage II, histological grade III/undifferentiated, no recurrence of disease, and live cases without cancer. No association of MSI status with genetic ancestry components was observed. MSI-targeted genes analyses showed the most frequently altered genes: ATM, EGFR, MRE11, ROCK1, and TGFBRII. There was a statistically significant difference in cancer-specific survival between cases according to MSI status. This study constitutes the most comprehensive analyses of the MSI impact on the Brazilian CRC. MSI+ frequency in Brazilian CRC agreed with the literature and was associated with several clinicopathological features related with less aggressive tumors, independently of their genetic ancestry.

Microsatellite Instability, Epstein-Barr Virus, and Programmed Cell Death Ligand 1 as Predictive Markers for Immunotherapy in Gastric Cancer.

Immunotherapy benefits selected cases of gastric cancer (GC), but the correlation between biomarkers and prognosis is still unclear. Fifty-two patients with GC who underwent immunotherapy were enrolled from June 2016 to December 2020. Their clinical features and biomarkers-microsatellite instability-high (MSI-H), programmed cell death ligand 1 (PD-L1) combined positive score (CPS), and Epstein-Barr encoding region (EBER)-were analyzed. Eight patients had MSI-H, five patients had EBER, 29 patients had CPS ≥ 1, and 20 patients had no biomarker. The overall response rates (ORRs) of the MSI-H, EBER, PD-L1 CPS ≥ 1, and all-negative group were 75%, 60%, 44.8%, and 15%, respectively. Compared with that of the all-negative group, progression-free survival (PFS) was better in the MSI-H (p = 0.018), CPS ≥ 5 (p = 0.012), and CPS ≥ 10 (p = 0.006) groups, but not in the EBER (p = 0.2) and CPS ≥ 1 groups (p = 0.35). Ten patients had combined biomarkers, CPS ≥ 1 with either MSI-H or EBER. The ORRs were 66.7% for CPS ≥ 1 and MSI-H and 75% for CPS ≥ 1 and EBER. PFS was better in patients with combined biomarkers (p = 0.01). MSI-H, EBER, and CPS are useful biomarkers for predicting the efficacy of immunotherapy.

Integrative analysis deciphers the heterogeneity of cancer-associated fibroblast and implications on clinical outcomes in ovarian cancers

Accumulating evidence has recognized that cancer-associated fibroblasts (CAFs) are major players in the desmoplastic stroma of ovarian cancer, modulating tumor progression and therapeutic response. However, it is unclear regarding the signatures of CAFs could be utilized to predict the clinical outcomes of ovarian cancer patients. To fill in this gap, we explored the intratumoral compartment of ovarian cancer by analyzing the single-cell RNA-sequencing (scRNA-seq) datasets of ovarian carcinoma samples, and identified two distinct CAFs (tumor-promoting CAF_c1 subtype and myofibroblasts-like CAF_c2 subtype). The clinical significance of CAF subtypes was further validated in The Cancer Genomics Atlas (TCGA) database and other independent immunotherapy response datasets, and the results revealed that the patients with a higher expression of CAF_c1 signatures had a worse prognosis and showed a tendency of resistance to immunotherapy. This work uncovered the signatures of the CAF_c1 subtype that could serve as a novel prognostic indicator and predictive marker for immunotherapy.

ITGB2 as a prognostic indicator and a predictive marker for immunotherapy in gliomas.

Glioma is the most common primary tumor in the brain, accounting for 81% of intracranial malignancies. Nowadays, cancer immunotherapy has become a novel and revolutionary treatment for patients with advanced, highly aggressive tumors. However, to date, there are no effective biomarkers to reflect the response of glioma patients to immunotherapy. In this study, we aimed to assess the clinical predictive value of ITGB2 in patients with glioma. The correlation between ITGB2 expression levels and glioma progression was explored and validated using data from CGGA, TCGA, GEO datasets, and patient samples from our hospital. Univariate and multivariate cox regression models were developed to determine the predictive role of ITGB2 on the prognosis of patients with glioma. The relationship between ITGB2 and immune activation was then analyzed. Finally, we predicted the immunotherapy response in both high and low ITGB2 expression subgroups. ITGB2 was significantly elevated in gliomas with higher malignancy and predicted poor prognosis. In multivariate analysis, the hazard ratio for ITGB2 expression (low versus high) was 0.71 with 95% CI (0.59-0.85) (P <0.001). Furthermore, we found that ITGB2 stratified glioma patients into high and low ITGB2 expression subgroups, exhibiting different clinical outcomes and immune activation status. At last, we demonstrated that glioma patients with high ITGB2 expression levels had better immunotherapy response. This study demonstrated ITGB2 as a novel predictor for clinical prognosis and response to immunotherapy in gliomas. Assessing expression levels of ITGB2 is a promising method to discover patients that may benefit from immunotherapy.

P34.08 Circulating Tumor Cell as a Predictive Marker for Immunotherapy in Advanced Non-Small Cell Lung Cancer

P34.08 Circulating Tumor Cell as a Predictive Marker for Immunotherapy in Advanced Non-Small Cell Lung Cancer

Identifying predictive biomarkers of CIMAvaxEGF success in non\u2013small cell lung cancer patients

BackgroundImmunosenescence biomarkers and peripheral blood parameters are evaluated separately as possible predictive markers of immunotherapy. Here, we illustrate the use of a causal inference model to identify predictive biomarkers of CIMAvaxEGF success in the treatment of Non–Small Cell Lung Cancer Patients.MethodsData from a controlled clinical trial evaluating the effect of CIMAvax-EGF were analyzed retrospectively, following a causal inference approach. Pre-treatment potential predictive biomarkers included basal serum EGF concentration, peripheral blood parameters and immunosenescence biomarkers. The proportion of CD8 + CD28- T cells, CD4+ and CD8+ T cells, CD4/CD8 ratio and CD19+ B cells. The 33 patients with complete information were included. The predictive causal information (PCI) was calculated for all possible models. The model with a minimum number of predictors, but with high prediction accuracy (PCI > 0.7) was selected. Good, rare and poor responder patients were identified using the predictive probability of treatment success.ResultsThe mean of PCI increased from 0.486, when only one predictor is considered, to 0.98 using the multivariate approach with all predictors. The model considering the proportion of CD4+ T cell, basal Epidermal Growth Factor (EGF) concentration, neutrophil to lymphocyte ratio, Monocytes, and Neutrophils as predictors were selected (PCI > 0.74). Patients predicted as good responders according to the pre-treatment biomarkers values treated with CIMAvax-EGF had a significant higher observed survival compared with the control group (p = 0.03). No difference was observed for bad responders.ConclusionsPeripheral blood parameters and immunosenescence biomarkers together with basal EGF concentration in serum resulted in good predictors of the CIMAvax-EGF success in advanced NSCLC. Future research should explore molecular and genetic profile as biomarkers for CIMAvax-EGF and it combination with immune-checkpoint inhibitors. The study illustrates the application of a new methodology, based on causal inference, to evaluate multivariate pre-treatment predictors. The multivariate approach allows realistic predictions of the clinical benefit of patients and should be introduced in daily clinical practice.

Abstract 5373: Circulating tumor cell as a predictive marker for immunotherapy in advnaced non-small cell lung cancer

Abstract Background: Circulating tumor cells (CTCs) have potential to provide minimally invasive way for the response monitoring of various cancer. This study aimed to investigate the feasibility of CTCs as a predictive marker for anti-PD-L1 immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: This study included 37 patients with advanced NSCLC receiving atezolizumab monotherapy as second-line or more from July to November 2019. Blood was collected in a K2-EDTA tube and CTCs were isolated and enriched by using CD-PRIMETM system which is antibody-independent size-based isolation method. By Bioview CCBS system, total CTCs (tCTCs) were identified by a sum of single EpCAM/CK-positive (sCTCs) and double EpCAM/CK-CD45-positive cells (dCTCs). Results: Among 26 response-evaluable patients, objective response rate (ORR) and disease control rate (DCR) were 11.5% (3/26) and 57.7% (15/26), respectively. At cycle 1 (C1), patients with progression (PD) showed higher sCTC count (median, 8.6 vs. 4.3, p=0.065) and sCTC-to-tCTC ratio (median %, 35.9 vs. 9.8, p=0.024) than those without PD. During treatment, tCTC and sCTC count showed significant increase from C1 to C2 (p=0.019 and p=0.022). The subgroup with high sCTC increase from C1 to C2 (more than 2-folds) showed higher DCR than subgroup with low sCTC increase (less than 2-folds) (88.9% vs. 44.4%, p=0.066). Patients with high sCTC-to-tCTC ratio at C1 showed worse progression-free survival (median, 2.1 months) than those with low sCTC-to-tCTC ratio (not reached, hazard ratio 2.87, 95% confidence interval: 1.06-7.75, p=0.082). Conclusion: The baseline sCTC count and sCTC increase (more than 2-folds) at the first 3-week after atezolizumab could be potential biomarkers to predict the disease progression and poor survival in advanced NSCLC. Citation Format: Cheol-Kyu Park, Joon-Young Yoon, Min-Suk Kim, Bo-Gun Koh, Hyun-Ju Cho, In-Jae Oh, Young-Chul Kim. Circulating tumor cell as a predictive marker for immunotherapy in advnaced non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5373.

High degree of heterogeneity of PD-L1 and PD-1 from primary to metastatic endometrial cancer

ObjectivePD-L1 and PD-1 are predictive markers for immunotherapy and increasingly relevant in endometrial cancer. The reported fraction of positive primary tumors has been inconsistent. We investigated the expression of PD-L1 and PD-1 in primary tumors, also stratified by MSI. As immunotherapy is foremost relevant for metastatic disease, PD-L1 and PD-1 expression was also assessed in corresponding metastatic lesions. MethodsPD-L1 and PD-1 was investigated in a prospective, population based endometrial cancer cohort of 700 patients with corresponding metastatic lesions from 68 and 74 patients respectively. Fresh tissue was used for gene expression analysis. ResultsIn primary tumors, PD-L1 and PD-1 are expressed in 59% and 63%, respectively, but with no impact on survival, nor when stratified for MSS and MSI. Expression patterns of PD-L1 and PD-1 are similar in MSI and MSS tumors. Available metastatic lesions show heterogeneous expression of PD-L1 and PD-1. In gene expression analysis several genes related to immunological activity, including CD274 (encoding for PD-L1), were upregulated in PD-1 positive tumors. ConclusionPD-L1 and PD-1 are frequently expressed in endometrial cancer and expression patterns are similar across MSS and MSI tumors. Expression in corresponding metastatic lesions is discordant compared to primary tumors. These findings are in particular relevant for treatment decisions in advanced and recurrent disease.

CSF1R and HCST: Novel Candidate Biomarkers Predicting the Response to Immunotherapy in Non-Small Cell Lung Cancer.

Objective:Precision immunotherapy in non-small cell lung cancer (NSCLC) have been the focus of tumor immunity research. The aim of this study is to identify novel candidate biomarkers predicting the response to immunotherapy in NSCLC.Methods:GSE126044 was obtained from Gene Expression Omnibus (GEO). According to the response to anti-PD-1 antibody, 2 groups were divided: response group and non-response group. Differentially expressed genes (DEGs) were screened using R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. ROC curves and possible pathways of the seed genes were further analyzed.Results:In total, 588 DEGs (487 upregulated DEGs and 101 downregulated) were identified. GO and KEGG analyses showed that upregulated DEGs were mainly enriched in immune response and cell adhesion pathways, while VEGF signaling pathway and metabolic pathways were mainly enriched in downregulated DEGs. In addition, CSF1 R and HCST showed more powerful predictive ability than PDL1. More importantly, these candidate genes were not only positively correlated with the expression of PDL1 and the infiltration of CD8+ T cells in the immune microenvironment, but also might improve the prognosis in lung squamous cell carcinoma.Conclusions:CSF1 R and HCST might be novel predictive markers for immunotherapy in NSCLC.

Correlation between K-RAS mutant subsets, TP53 mutation, and PD-L1 status in non-small cell lung cancer (NSCLC).

e14272 Background: K-RAS is a non-targetable mutation with no established predictive value. However, PD-L1 is the only approved predictive marker for immunotherapy in NSCLC. K-RAS mutation like PD-L1 has been associated with smoking. TP53 and K-RAS mutations have been identified in aggressive neoplasms. We hypothesized that K-RAS mutant NSCLC has higher PD-L1 expression suggestive of improved response to immunotherapy. Methods: The Caris database from 2016 - 2018 was queried and patients with NSCLC were identified. ≥1% staining for PD-L1 (22c3 antibody) was considered positive. PD-L1 expression as well as K-RAS and TP53 mutation status were analyzed and correlation between different variables were identified using ANOVA. Results: We identified 8,471 patients with NSCLC, where 66% had TP53 mutation and 26.9% had K-RAS mutation; both mutations were identified in 12% of the patients. In the subset of combined K-RAS and TP53 mutations there were 71.48% having positive PD-L1 expression with female predominance 1.4:1. Of the eight main K-RAS mutation subsets, G12C subset was the most common. Compared to other K-RAS subtypes, G12C was associated with the higher occurrence of PD-L1 positivity (62.68%,p &lt; 0.04; Table). Conclusions: In comparison to other subsets of K-RAS mutation, G12C had the highest occurrence of PD-L1 expression, suggestive of improved response to immunotherapy. However, the subset of patients with combined K-RAS and TP53 mutations had a higher occurrence for the PD-L1 positive status of 71.48%. [Table: see text]

Dynamic relationships among tumor, immune response, and microbiota

Recently, the analysis of microbiota has been of interest not only for the clarification of the molecular mechanisms of disease etiology, but also the discovery of novel strategies for treatment. Following the development of "next-generation" sequencing, novel areas have been discovered in microbiota; however, in oncology, the relationships between microbiota and cancer have not been fully clarified. In recent literature, surprisingly, detection of gut microbiota in tumor issue itself has been reported. Microbiota might play an important role in carcinogenesis. However, this phenomenon is not well understood, and research in this area has just begun. In the past five years, a paradigm shift has occurred in cancer treatment due to immunotherapy. Immunotherapy has made cure possible even in advanced cancer patients with not only melanoma but also non-small cell lung cancer and others. In this review, we discuss the mechanisms of novel immunotherapies, checkpoint inhibitors, and the relationship between microbiota and immunotherapy. It is of significance to clarify this relationship because it may lead to the discovery of predictive markers for immunotherapy and promote clinical efficacy. Finally, we also mention our activities in the construction of a big database for information on immunotherapy and microbiota, which may lead to excellent possibilities of discovering novel strategies for more effective cancer treatments, and may accelerate the alteration of cancers to the classification of chronic nonfatal disease.

DNA mismatch repair in cancer.

Microsatellite instability (MSI) refers to the hypermutator phenotype secondary to frequent polymorphism in short repetitive DNA sequences and single nucleotide substitution, as consequence of DNA mismatch repair (MMR) deficiency. MSI secondary to germline mutation in DNA MMR proteins is the molecular fingerprint of Lynch syndrome (LS), while epigenetic inactivation of these genes is more commonly found in sporadic MSI tumors. MSI occurs at different frequencies across malignancies, although original methods to assess MSI or MMR deficiency have been developed mostly in LS related cancers. Here we will discuss the current methods to detect MSI/MMR deficiency with a focus of new tools which are emerging as highly sensitive detector for MSI across multiple tumor types. Due to high frequencies of non-synonymous mutations, the presence of frameshift-mutated neoantigens, which can trigger a more robust and long-lasting immune response and strong TIL infiltration with tumor eradication, MSI has emerged as an important predictor of sensitivity for immunotherapy-based strategies, as showed by the recent FDA's first histology agnostic-accelerated approval to immune checkpoint inhibitors for refractory, adult and pediatric, MMR deficient (dMMR) or MSI high (MSI-H) tumors. Moreover, it is known that MSI status may predict cancer response/resistance to certain chemotherapies. Here we will describe the complex interplay between the genetic and clinical-pathological features of MSI/dMMR tumors and the cancer immunotherapy, with a focus on the predictive and prognostic role of MMR status for immune checkpoint inhibitors (ICIs) and providing some suggestions on how to conceive better predictive markers for immunotherapy in the next future.

C-reactive protein (CRP) as a predictive marker for immunotherapy in lung cancer.

e20623Background: The PD1-inhibitor nivolumab is approved in second line metastatic squamous cell carcinomas of the lung, and has in clinical trials shown response rates of around 20%. Overexpressi...

The Role of Predictive Molecular Biomarkers for the Treatment of Metastatic Colorectal Cancer

Colorectal cancer (CRC) is a major public health problem in the USA and globally. Over the past 20 years, significant advances have been made in the treatment of patients with metastatic colorectal cancer (mCRC). Recent efforts have focused on developing molecular biomarkers to further define the subset of patients with mCRC who would derive a substantial benefit from anti-epidermal growth factor receptor (EGFR) therapy. Activating mutations in KRAS and NRAS are a predictive marker for resistance to anti-EGFR therapy in mCRC. BRAFV600E and PIK3CA mutations have been reported as negative predictive markers for anti-EGFR therapy in mCRC. Microsatellite instability and immunologic biomarkers may be predictive markers for immunotherapy, including immune-checkpoint inhibitors in the near future. Next-generation sequencing technology is a powerful new tool for the discovery of predictive molecular biomarkers and to facilitate the delivery of personalized medicine. Herein, we review the current status of predictive molecular biomarker research in the treatment of mCRC.

Possible Predictive Markers of Immunotherapy in Esophageal Cancer: Retrospective Analysis of a Randomized Study

The aim of this report is to evaluate retrospectively the data from a prospective randomized study of 158 esophageal cancer patients who actually completed therapy with protein-bound polysaccharide P (PSK) and the 5-year survivals with and without raised alpha 1-antichymotrypsin and sialic acid levels to determine the value of these parameters in predicting effectiveness of immunotherapy. There was a significant difference in survival between the patients with and without PSK therapy. The survival of the radiochemotherapy plus PSK group treated for > 3 months was significantly better than that of the radiochemotherapy group. Among the patients with abnormal levels of alpha 1-antichymotrypsin and sialic acid, those who received PSK may have a significantly better survival than those without PSK. These results indicate that the preoperative serum levels of alpha 1-antichymotrypsin and sialic acid may possibly predict the effectiveness of immunotherapy using PSK.