Cancer is one of the primary causes of mortality globally, and the discovery of new anticancer drugs is the most important need in recent times. Natural products have been recognized as effective in ...fight against various diseases including cancer for over 50 years. Plants and microbes are the primary and potential sources of natural compounds to fight against cancer. Moreover, researches in the field of plant-based natural compounds have moved towards advanced and molecular level understandings from the last few decades, leading to the development of potent anticancer agents. Also, plants have been accepted as abundant and prosperous sources for the development of novel therapeutic agents for the management and prevention of different cancer types. The high toxicity of some cancer chemotherapy drugs, as well as their unfavorable side effects and drugs resistance, drives up the demand for natural compounds as new anticancer drugs. In this detailed evidence-based mechanistic review, facts and information about various medicinal plants, their bioactive compounds with their potent anticancer activities against different cancers have been gathered, with further approach to represent the molecular mechanism behind the anticancer activity of these plants. This review will be beneficial for investigators/scientists globally involved in the development of natural, safe, effective, and economical therapeutic agents/drugs against various cancers. This might be an important contribution in the field of drug discovery, where drugs can be used alone or in combination to increase the efficacy of newly synthesized drugs.
Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and ...metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials.
Functions of Shp2 in cancer Zhang, Jie; Zhang, Fei; Niu, Ruifang
Journal of cellular and molecular medicine,
September 2015, Letnik:
19, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Diagnostics and therapies have shown evident advances. Tumour surgery, chemotherapy and radiotherapy are the main techniques in treat cancers. Targeted therapy and drug resistance are the main focus ...in cancer research, but many molecular intracellular mechanisms remain unknown. Src homology region 2‐containing protein tyrosine phosphatase 2 (Shp2) is associated with breast cancer, leukaemia, lung cancer, liver cancer, gastric cancer, laryngeal cancer, oral cancer and other cancer types. Signalling pathways involving Shp2 have also been discovered. Shp2 is related to many diseases. Mutations in the ptpn11 gene cause Noonan syndrome, LEOPARD syndrome and childhood leukaemia. Shp2 is also involved in several cancer‐related processes, including cancer cell invasion and metastasis, apoptosis, DNA damage, cell proliferation, cell cycle and drug resistance. Based on the structure and function of Shp2, scientists have investigated specific mechanisms involved in cancer. Shp2 may be a potential therapeutic target because this phosphatase is implicated in many aspects. Furthermore, Shp2 inhibitors have been used in experiments to develop treatment strategies. However, conflicting results related to Shp2 functions have been presented in the literature, and such results should be resolved in future studies.
Genetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, ...hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or moderate increased risk of developing breast and/or ovarian cancer. Here, we assess the genetic variation and tumor characteristics in a large cohort of women with suspected HBOC in a clinical oncogenetic setting.
Women with suspected HBOC referred from all oncogenetic clinics in Sweden over a six-year inclusion period were screened for PVs in 13 clinically relevant genes. The genetic outcome was compared with tumor characteristics and other clinical data collected from national cancer registries and hospital records.
In 4622 women with breast and/or ovarian cancer the overall diagnostic yield (the proportion of women carrying at least one PV) was 16.6%. BRCA1/2 PVs were found in 8.9% of women (BRCA1 5.95% and BRCA2 2.94%) and PVs in the other breast and ovarian cancer predisposition genes in 8.2%: ATM (1.58%), BARD1 (0.45%), BRIP1 (0.43%), CDH1 (0.11%), CHEK2 (3.46%), PALB2 (0.84%), PTEN (0.02%), RAD51C (0.54%), RAD51D (0.15%), STK11 (0) and TP53 (0.56%). Thus, inclusion of the 11 genes in addition to BRCA1/2 increased diagnostic yield by 7.7%. The yield was, as expected, significantly higher in certain subgroups such as younger patients, medullary breast cancer, higher Nottingham Histologic Grade, ER-negative breast cancer, triple-negative breast cancer and high grade serous ovarian cancer. Age and tumor subtype distributions differed substantially depending on genetic finding.
This study contributes to understanding the clinical and genetic landscape of breast and ovarian cancer susceptibility. Extending clinical genetic screening from BRCA1 and BRCA2 to 13 established cancer predisposition genes almost doubles the diagnostic yield, which has implications for genetic counseling and clinical guidelines. The very low yield in the syndrome genes CDH1, PTEN and STK11 questions the usefulness of including these genes on routine gene panels.
Clear cell renal cell carcinoma (CCRCC) is characterized by a highly metastatic potential. The stromal communication between stem cells and cancer cells critically influences metastatic dissemination ...of cancer cells.
The effect of exosomes isolated from cancer stem cells (CSCs) of CCRCC patients on the progress of epithelial-mesenchymal transition (EMT) and lung metastasis of CCRCC cells were examined.
CSCs exosomes promoted proliferation of CCRCC cells and accelerated the progress of EMT. Bioactive miR-19b-3p transmitted to cancer cells by CSC exosomes induced EMT via repressing the expression of PTEN. CSCs exosomes derived from CCRCC patients with lung metastasis produced the strongest promoting effect on EMT. Notably, CD103
CSC exosomes were enriched in tumor cells and in lung as well, highlighting the organotropism conferred by CD103. In addition, CD103
exosomes were increased in blood samples from CCRCC patients with lung metastasis.
CSC exosomes transported miR-19b-3p into CCRCC cells and initiated EMT promoting metastasis. CD103
acted to guide CSC exosomes to target cancer cells and organs, conferring the higher metastatic capacity of CCRCC to lungs, suggesting CD103
exosomes as a potential metastatic diagnostic biomarker. ᅟ.
Platinum-based chemotherapy is standard-of-care first-line treatment for advanced urothelial carcinoma. However, progression-free survival and overall survival are limited by chemotherapy resistance.
...In a phase 3 trial, we randomly assigned patients with unresectable locally advanced or metastatic urothelial cancer who did not have disease progression with first-line chemotherapy (four to six cycles of gemcitabine plus cisplatin or carboplatin) to receive best supportive care with or without maintenance avelumab. The primary end point was overall survival, assessed among all patients who underwent randomization (overall population) and among those with tumors positive for programmed cell death ligand 1 (PD-L1). Secondary end points included progression-free survival and safety.
Among all 700 patients who underwent randomization, the addition of maintenance avelumab to best supportive care significantly prolonged overall survival as compared with best supportive care alone (control). Overall survival at 1 year was 71.3% in the avelumab group and 58.4% in the control group (median overall survival, 21.4 months vs. 14.3 months; hazard ratio for death, 0.69; 95% confidence interval CI, 0.56 to 0.86; P = 0.001). Avelumab also significantly prolonged overall survival in the PD-L1-positive population; overall survival at 1 year was 79.1% in the avelumab group and 60.4% in the control group (hazard ratio, 0.56; 95% CI, 0.40 to 0.79; P<0.001). The median progression-free survival was 3.7 months in the avelumab group and 2.0 months in the control group in the overall population (hazard ratio for disease progression or death, 0.62; 95% CI, 0.52 to 0.75) and 5.7 months and 2.1 months, respectively, in the PD-L1-positive population (hazard ratio, 0.56; 95% CI, 0.43 to 0.73). The incidence of adverse events from any cause was 98.0% in the avelumab group and 77.7% in the control group; the incidence of adverse events of grade 3 or higher was 47.4% and 25.2%, respectively.
Maintenance avelumab plus best supportive care significantly prolonged overall survival, as compared with best supportive care alone, among patients with urothelial cancer who had disease that had not progressed with first-line chemotherapy. (Funded by Pfizer and Merck Darmstadt, Germany; JAVELIN Bladder 100 ClinicalTrials.gov number, NCT02603432.).
Excess body weight has been established as a risk factor for at least twelve cancer sites, though questions remain as to the timing of associations for adiposity and cancer risk throughout the life ...course. We conducted a narrative review summarizing existing evidence to provide insights into the complex timing relationship between adiposity and risk of seven common obesity-related cancers. We considered five types of studies, including traditional epidemiologic studies examining adiposity at different time points, studies examining weight gain in specific life phases, studies examining weight loss over a period including from bariatric surgery, life course trajectory analysis, and Mendelian randomization studies. The results showed that lifetime excess body weight is associated with increased risk of cancers of endometrium, colorectum, liver, kidney, and pancreas. Early life obesity is one of the strongest risk factors for pancreatic cancer but less directly important than adult obesity for endometrial and kidney cancer. Interestingly, heavy weight during childhood, adolescence, and early adulthood is protective against pre- and postmenopausal breast cancer and possibly advanced prostate cancer. It is apparent that preventing weight gain later in adulthood would likely reduce risk of many cancers, including postmenopausal breast cancer, endometrial cancer, colorectal cancer (especially in men), liver cancer, kidney cancer, and probably advanced prostate cancer. Furthermore, weight loss even late in life may confer benefits for cancers of breast, endometrium, colorectum, and liver among patients with obesity, as mostly demonstrated by studies of bariatric surgery. Overall, maintaining a healthy weight throughout the life course will help prevent a large number of cancers.
Familial risks of breast cancer (BC) are well established but whether BC clusters with other, i.e. discordant, cancers is less certain but of interest for the identification of common genetic and ...possible environmental factors contributing to a general cancer susceptibility. We apply a novel approach to search for familial associations of BC with other (discordant) cancers based on the Swedish Family‐Cancer Database. Relative risks (RRs) were calculated for BC in families with increasing numbers of patients with discordant cancer X, and conversely, familial RRs for cancer X in families with increasing numbers of BC patients. Joint p‐values were calculated from independent analyses. The total number of familial BCs was 12,266, 14.9% with one first‐degree relative with BC and 1.2% with at least 2 affected relatives. Ovarian and prostate cancers showed the strongest associations with BC (p‐value <10−11). The p‐value for melanoma was <10−6, for stomach and male colorectal cancer <2.5 × 10−6, for cancer of unknown primary <2.5 × 10−5 and for lung cancer <5 × 10−5. Significance level <5 × 10−4 was reached with pancreatic cancer. The remaining associations (p < 0.0025) included thyroid, endometrial, testicular, eye cancers (uveal melanoma), nervous system and endocrine tumors and non‐Hodgkin lymphoma. The RR for BC increased by increasing numbers of patients with any cancer in family members and it reached 1.62 when three or more family members were affected. The results suggest that BC shares susceptibility with a number of other cancers. This might alert genetic counselors and challenge approaches for gene and gene–environment identification.
What's new?
It is well known that first‐degree relatives of breast‐cancer (BC) patients have also an increased risk of breast and ovarian cancer. But what about other, seemingly unrelated types of cancer? In our large study, the authors found that families with BC have also significantly higher rates of several other cancers, including melanoma, stomach cancer and leukemia. The converse was also true – families with other cancers have also increased rates of BC. These results suggest that BC shares genetic or environmental susceptibility factors with other types of cancer.
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