Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs); where do they stand in tumorigenesis and how they can change the face of cancer therapy?

The tumor microenvironment (TME) and its components have recently attracted tremendous attention in cancer treatment strategies, as alongside the genetic and epigenetic alterations in tumor cells, TME could also provide a fertile background for malignant cells to survive and proliferate. Interestingly, TME plays a vital role in the mediation of cancer metastasis and drug resistance even against immunotherapeutic agents. Among different cells that are presenting in TME, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) have shown to have significant value in the regulation of angiogenesis, tumor metastasis, and drug-resistance through manipulating the composition as well as the organization of extracellular matrix (ECM). Evidence has shown that the presence of both TAMs and CAFs in TME is associated with poor prognosis and failure of chemotherapeutic agents. It seems that these cells together with ECM form a shield around tumor cells to protect them from the toxic agents and even the adaptive arm of the immune system, which is responsible for tumor surveillance. Given this, targeting TAMs and CAFs seems to be an essential approach to potentiate the cytotoxic effects of anti-cancer agents, either conventional chemotherapeutic drugs or immunotherapies. In the present review, we aimed to take a deep look at the mechanobiology of CAFs and TAMs in tumor progression and to discuss the available therapeutic approaches for harnessing these cells in TME.

Primary Liver Cancer in Golestan Province, Northeastern Iran: 13-Year Experience of Golestan Population-Based Cancer Registry (GPCR).

BACKGROUND: Liver cancer (LC) is among the most common and fatal cancers worldwide. A four-fold increasing trend is reported for LC age-standardized mortality rate (ASMR) in Iran within 1990-2015. In the present study, we aimed to report the incidence rate of LC during the 13-year establishment of the Golestan population-based cancer registry (GPCR). METHODS: Age-standardized incidence rate (ASIR) per 100000 person-years was calculated using CanReg5 software. The Joint point regression analysis was used to assess the temporal trends in incidence rate of LC. RESULTS: During the study period, GPCR registered 575 of LC cases, of which 373 (64.9%) were men and 297 (51.6%) lived in rural areas. The mean (SD) age of LC in men and women were 60.3 (17.2) and 58.0 (17.1), respectively. The ASIR of LC was significantly higher in men than women (4.7 vs. 2.6; P value<0.01) and a minimal increasing trend in LC incidence was observed in both sexes. The incidence rate of LC was significantly higher in rural areas compared to the urbans (3.91 vs. 3.40; P value=0.04). In the last 13 years, rural population had a significant increasing trend in ASIR of LC (average annual percent change [AAPC]=7.85, P value=0.005). CONCLUSION: LC was more prevalent in men among both urban and rural populations. The results showed a significant increasing trend in rural areas that requires Golestan health care system to take action in controlling the burden of LC in rural areas.