Clinical Oncology

[Why don’t immune checkpoint inhibitors work in colorectal cancer?]

SHI Yuequan, ZOU Zifang, KERR David

MAY 10, 2017

Clinical Oncology - 2017;4(02)

[In recent years, immune checkpoint inhibitors have been shown to be effective in treating manifold types of cancer but less robust in colorectal cancer (CRC). While, the subgroup of CRC with microsatellite instability (MSI; also termed as mismatch repair defi cient) showed a moderate response to Pembrolizumab in a single arm phase II clinical trial, microsatellite stable (MSS) cancers were unresponsive. Possible mechanisms that affect immune response in colorectal cancer will be reviewed in this article. We will also propose that histone deacetylase (HDAC) inhibition may reverse the immune editing commonly seen in advanced CRC and render them sensitive to immune checkpoint blockade.]



Further articles in this publication

Clinical Oncology

[News from the World]

Clinical Oncology

[Adjuvant treatment of breast cancer]


[Choice of optimal adjuvant treatment has been based on present debates, doubts and commit offence against processing or existing evidences. Clinical research has been resulted changes and renewal of practice decisions continuously. 3rd Breast Cancer Consensus Conference held on Kecskemét last year corresponded by Hungarian experts of the fi eld has given up to date and well-defi ned guideline. Present paper try to give a summary of adjuvant treatment courses for early breast cancer in consideration of last results of research since then.]

Clinical Oncology

[Signaling pathways in cancer stem cells (Notch, Hedgehog, Wnt)]


[OThe key regulators in the embryonic life, and later in the differentiation of tissues and organs are the evolutionary reserved signalling pathways, as Notch, Hedgehog and Wnt. Mutations of these pathways have been identifi ed in many tumor types, increasing the risk to the appearance of cancer stem cells (CSC), with very similar geno- and phenotype as normal stem cells have. Such CSCs with stemness functions can be developed not only from normal stem cells, but also from progenitor and differentiated cells. The main characteristics of CSC are the self maintenance, slow growth rate, very effective DNA-repair system, etc. All of these can contribute to the resistance. Further problems are the low number of CSC in the whole tumor mass, which makes rather diffi cult to achieve the effective drug concentration in CSC. The mentioned ancient pathways interact with many other pathways to form a network, which can infl uence the strategy of therapy. No doubt, that these pathways are promising targets, however, till now the clinical effectiveness is very low due to some reasons mentioned above. Nevertheless, some drugs are already in clinical use, either as monotherapy or part of the combinations. Little is known about the relationship between the pathways and the microenvironment, which has an outstanding role in the cellular activities, sometimes resulting opposite output. It is a great challenge to design effective drugs against CSC, similarly to fi nd reliable predictive biomarkers, which unfortunately still missing, since a reasonable drug-marker interactions would speed up the personalized treatment.]

Clinical Oncology

[Paleo-oncology - messages from the past]

MOLNÁR Erika, MARCSIK Antónia, PÁLFI György, ZÁDORI Péter, BUCZKÓ Krisztina, TAKÁCS Vellainé Krisztina, HAJDU Tamás

[Nowadays, cancer is one of the greatest challenges facing mankind. However, there is still no consensus among researchers regarding the antiquity of cancer. Written sources and paleo-oncological studies may help to answer this question. The aim of this study is to present data on the history of cancer based on historical sources, literature data and own research fi ndings. Early historical sources indicate that cancer was already known in antiquity. Paleopathological studies of animal and human fossils show that malignant bone tumors were present in ancient times, although the frequency of the disease was seemingly very low. The increasing number of unearthed fossils and the use of modern diagnostic tools have led to a rise of the number of diagnosed cancer cases. Our comprehensive paleo-oncological study, focusing on the occurrence and frequency change of malignant tumors in historic populations of Hungary was based on the analysis of skeletal remains belonging to 11,000 individuals dated from the Early Neolithic to the late medieval period. During the analysis macromorphological, modern imaging and histological methods were applied. As a result of the extensive investigations osteological evidences of malignant bone tumors were identifi ed in 39 cases. Neoplastic bone diseases were present in all studied historical periods and there were no differences in their occurrence and frequency between the different archaeological periods.]

Clinical Oncology


A szerkesztők

All articles in the issue

Related contents

Lege Artis Medicinae

[Specialists’ opinions about the introduction of colorectal cancer screening ]


[ INTRODUCTION - The number of new cases of colorectal cancer is over 10 000 and there are around 5000 deaths per year in Hungary. A nationwide colon cancer screening program was launched in 2018. AIMS - Concerning the upcoming national screening, our aim was to explore attitudes, preferences and knowledge of specialists (family medicine, gastroenterology, surgery, oncology, pathology) who will be engaged in screening, diagnosis and treatment of colorectal cancer. METHOD - Before the start of the program we conducted semi-structured interviews with 20 representatives of specialties mentioned above. Interview-questions focused on knowledge (epidemiology, screening methods, program-related), preferences (screening method, protocol) and impact of the program on medical practice. Quan­ti­ta­tive and qualitative methods were used for analysis. RESULTS - Incidence of colon cancer was well known but its mortality in Hungary was underestimated. The public health significance of colorectal cancer scored 7 on a 10-point Likert scale and all participants agreed with introduction of the program. 12 people knew the chosen protocol (two-stage), only a single person mentioned one-stage (colonoscopy), and 7 had no information. 16 people prefer colonoscopy as the best screening method. 11 support two-stage protocol, 5 do not support but accept it, 4 would only accept the one-stage approach. 13 people think their duties will increase considerably. CONCLUSIONS - Our review partners consider colorectal screening in Hungary as an initiative to be supported. They expect increase of workload in their everyday medical practice and assume that the current endoscopic capacity will be overburdened. The majority prefers two-stage protocol because of cost-effectiveness while arguing that the colonoscopy has a bad reputation among the general population, nevertheless they consider colonoscopy as the best method of screening. ]

Lege Artis Medicinae

[Systemic adjuvant pharmacotherapy of colorectal cancer]


[Colorectal cancer is one of the most frequent cancer in the postindustrial world; its most common form is adenocarcinoma. In Hungary, colorectal cancer has the second highest mortality among tumours. If diagnosed early, it might be successfully treated by surgery, however, chemotherapy is necessary to prevent tumor relapse and development of metastases and achieve adequate palliation. In the past few years, adjuvant treatment of colorectal cancer has improved substantially. Many new drugs have been developed, which are also being used in combination with previously known agents. This article will discuss the novelties in the field of adjuvant chemotherapy for colorectal cancer and the main guidelines of adjuvant treatment.]

Lege Artis Medicinae


LAKATOS László, LAKATOS Péter László

[Colorectal cancer is the second leading cause of cancer mortality in developed countries; in Hungary, the mortality has almost tripled in the past four decades. A decrease in mortality can only be expected from a consistently applied diagnostic and management strategy, including preventive measures. Primary prevention is defined as dietary, medicinal and lifestyle actions that can reduce the risk of developing cancer in people with average risk. Secondary prevention is the prophylactic treatment of high-risk patients or praecancerous lesions; tertiary prevention is the prevention of recurrence in patients cured of colorectal cancer. Drugs or dietary supplements used for chemoprevention block, delay or reverse the process of carcinogenesis. The most important drugs used for chemoprevention are aspirin and nonsteroidal anti-inflammatory drugs. Long-term administration of these drugs reduces the risk of developing colorectal cancer or adenoma both in the high-risk and in the average-risk population. The risk-lowering effect seems to be in positive correlation with the dose and the duration of use. Other chemoprophylactic drugs such as calcium, folate, oestrogen and antioxidants, as well as 5-aminosalicylates in patients with ulcerative colitis are also discussed in this review. Based on the current knowledge, chemoprophylaxis of colorectal cancer is recommended as secondary prevention in patients at high risk (e.g., familial adenomatous polyposis, extensive ulcerative colitis). In contrast, based on adverse event profile and cost-effectiveness analysis, primary prevention with chemopreventive drugs is currently not recommended in the averagerisk population.]

Clinical Oncology

[How the molecular informations infl uence the therapeutic strategy against colorectal cancer?]

AXEL Grothey

[Colorectal cancer is not a homogenous disease, but it has different subgroups based on their molecular characteristics. NCCN and ESMO guidelines emphasize the importance of the determination of RAS and BRAF mutations in those patients who are intended to treat with targeted therapy. The increase in knowledge on the molecular changes will help to design and start a new generation of clinical trials, which will be designed not on their randomization of large groups of unselected patients, but rather on the consideration of the molecular subgroups determined before introducing therapy.]


[The role of calcium in the chemoprevention of colorectal cancer]


[One of the most exciting research areas of the past decade has concerned the chemoprevention of colorectal cancer (CRC). Numerous clinical studies have been conducted on the preventive role of NSAIDs, high fibre intake, selenium, phytooestrogens, hormone replacement therapy, antioxidants, COX-inhibitors, folic acid and calcium, however, their results are controversial. Among the suggested chemopreventive agents, the preventive role of calcium is supported by the strongest evidence.This paper aims to review the available facts on the role of calcium. Recent studies suggest that appropriate calcium intake may partially counterbalance the effect of the genes that contribute to the development of CRC. Experimental data show that calcium directly influences the expression of several genes involved in tumorigenesis and that it is also involved in a number of signalling pathways that control cell proliferation, differentiation and apoptosis.These effects mostly arise through the activation of the calcium sensing receptor. The main goal of this review is to draw attention to the established chemopreventive role of calcium in CRC. Published data suggest that a lifelong daily calcium intake between 1200 to 1500 mg (even 2000 mg in high risk groups) would significantly decrease the incidence of CRC by inhibition of tumorigenesis.]