Cancer Statistics in I.R. Iran in 2020

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Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches

According to the Global Cancer Statistics 2020, colorectal cancer (CRC) represents the third most frequent malignancy worldwide, and is the second in terms of mortality [...]

Hematological malignancies in the Northwest Ethiopia

Background The effect of malignant diseases is increasing globally, particularly in developing countries as shown by recent cancer statistics from the world health organization reports. It is anticipated that with an increase in life expectancy consequent upon the improved standard of living and increasing urbanization, the burden of hematological malignancies in sub-Saharan Africa particularly in Ethiopia is likely to increase recently. Therefore, this study was aimed to determine the incidence and trend of hematological malignancy in Northwest Ethiopia. Methods A facility-based retrospective study was conducted from 2015 to 2019 at the University of Gondar and Bahir-Dar Felegehiwot comprehensive specialized hospitals. Hematological malignancy data were collected by using a data collection sheet that was consisted of patients’ socio-demography, clinical, and laboratory data. Then, data were entered into Epi-info 3.5.1 and exported to SPSS version 20 for analysis. Skewness and kurtosis were used to check data distribution. Descriptive statistics were summarized as percentages, means, and standard deviations of background variables, and the trend were analyzed. Results In this study, a total of 1,342 study participants were included. The mean age of study participants was 41.49 ± 16.3 years with a range of 1 to 92 years. About 58.3%, 52.2%, and 80% of the cases were observed among males, 18–45 age group, and urban residences, respectively. Of the total cases, 92.9% and 7.1% were lymphoma and leukemia, respectively. On the other hand, from lymphoma cases, 72.3% and 27.7% were HL and NHL, respectively while from leukemic cases, 61.1%, 23.2, 6.3%, 4.2%, and 5.3% were CLL, ALL, CML, AML, and other HM types, respectively. In this study, there was no trend. Conclusion We concluded that lymphoma was the dominant type of hematological malignancy observed in northwest Ethiopia. The study indicated that the majority of cases were observed among male, urban residents, and adult populations aged 18–45 years. Therefore, special focus should be given to the highly affected population. Further, a prospective cohort study should be conducted for a better understanding of the prevalence and associated factors to it.

Stemness, Inflammation and Epithelial–Mesenchymal Transition in Colorectal Carcinoma: The Intricate Network

In global cancer statistics, colorectal carcinoma (CRC) ranks third by incidence and second by mortality, causing 10.0% of new cancer cases and 9.4% of oncological deaths worldwide. Despite the development of screening programs and preventive measures, there are still high numbers of advanced cases. Multiple problems compromise the treatment of metastatic colorectal cancer, one of these being cancer stem cells—a minor fraction of pluripotent, self-renewing malignant cells capable of maintaining steady, low proliferation and exhibiting an intriguing arsenal of treatment resistance mechanisms. Currently, there is an increasing body of evidence for intricate associations between inflammation, epithelial–mesenchymal transition and cancer stem cells. In this review, we focus on inflammation and its role in CRC stemness development through epithelial–mesenchymal transition.

Identifying Novel Causes of Cancers to Enhance Cancer Prevention: New Strategies are Needed

The burden of cancer from a clinical, societal, and economic viewpoint continues to increase in all parts of the world, along with much debate regarding how to confront this. Projected increases in cancer indicate a 50% increase in the numbers of cases over the next two decades, with the greatest proportional increase in low- and medium-income settings. In contrast to the historic high cancer burden due to viral and bacterial infections in these regions, future increases are expected to be due to cancers linked to ‘westernization’ including breast, colorectum, lung, and prostate cancer. Identifying the reasons underlying these increases will be paramount to informing prevention efforts. Evidence from epidemiological and laboratory studies conducted in high income countries over the last 70 years have led to the conclusion that about 40% of the cancer burden is explained by known risk factors, the two most important being tobacco and obesity in that order, raising the question of what is driving the rest of the cancer burden. International cancer statistics continue to show that about 80% of the cancer burden in high income countries could be preventable in principle, implying that there are important environmental or lifestyle risk factors for cancer that have not yet been discovered. Emerging genomic evidence from population and experimental studies points to an important role for non-mutagenic promoters in driving cancer incidence rates. New research strategies and infrastructures that combine population-based and laboratory research at a global level are required to break this deadlock.

285 Breaking through the resistance of breast cancer to immune checkpoint blockers in a unique mouse model of HR+ disease

BackgroundHormone receptor (HR)+ breast cancer (BC) causes most BC-related deaths in the US.1 Standard treatment for non-metastatic disease involves surgery plus adjuvant hormonotherapy. However, approximately 50% of patients ultimately relapse and require additional lines of treatment including chemotherapy, which is unfortunately associated with limited clinical benefits and severe toxicity. In HR+ BC patients, the efficacy of immunotherapy has also been disappointing so far. Indeed, objective responses to PD-1 blockade with pembrolizumab in women with HR+ BC have been in the range of 5–10%, with no clear advantage on survival. Thus, resistance to PD-1 blockers constitutes a major obstacle towards the implementation of immunotherapy in HR+ BC patients.MethodsTo obtain insights into the immunological alterations accompanying disease relapse in HR+ BC exposed to PD-1 blockade, we harnessed a unique endogenous model of BC driven in immunocompetent mice by progesterone and a carcinogen. This model recapitulates key aspects of human luminal B BC, including a relatively ´cold´ microenvironment, hence limited sensitivity to PD-1 blockade.2 We undertook an in-depth characterization of the tumors (by DNAseq and RNAseq) and systemic (by flow cytometry on the splenic compartment) immune microenvironment of C57BL/6 female mice bearing tumors that recovered normal growth after PD-1 treatment.ResultsThere was no clear difference after PD-1 blockade at the systemic level in the myeloid, or lymphoid compartments; or in the activation of T cells, nor their capacity to degranulate upon ex vivo stimulation. Whole exome sequencing showed a higher mutational burden in PD-1 treated tumors after relapse. At the gene expression level, unsupervised analysis showed a clustering independent of the treatment groups, probably due to the heterogeneity of the model. Targeted pathway analysis with supervised clustering showed however differences in immune pathways that are currently further investigated, and results will be available shortly.ConclusionsBreaking through resistance of HR+ tumors to PD-1 blockers can direct strategies to overcome resistance in HR+ BC patients, the majority of BC patients. If successful, this can inform therapeutic approaches to enable superior therapeutic responses in patients with HR+ BC, hence significantly reducing BC-related deaths.ReferencesSiegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7–30.Buque A, Bloy N, Perez-Lanzon M, Iribarren K, Humeau J, Pol JG, Levesque S, Mondragon L, Yamazaki T, Sato A, Aranda F, Durand S, Boissonnas A, Fucikova J, Senovilla L, Enot D, Hensler M, Kremer M, Stoll G, Hu Y, Massa C, Formenti SC, Seliger B, Elemento O, Spisek R, Andre F, Zitvogel L, Delaloge S, Kroemer G, Galluzzi L. Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer. Nat Commun 2020;11:3819.Ethics ApprovalThis study was approved by Weill Cornell Medical College’s Ethics Board; approval number 2018–0053.