Tagged: Cancer Research

Trending With Impact: Novel Biomarkers in Bladder Cancer

June 4, 2021

Researchers from the University of Houston and UT Southwestern Medical Center conducted a study which aimed to screen urine for potentially useful protein biomarkers of bladder cancer.

The Trending with Impact series highlights Oncotarget publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Oncotarget.com.

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Bladder cancer is four times more common among men than women, and it is the sixth most common cancer diagnosis in the United States. However, researchers have found that cystoscopy—the primary method physicians use to diagnose patients with bladder cancer—is relatively invasive, expensive, and has the potential to cause urinary tract infections.

“In contrast, urine is a noninvasive and readily available biological fluid that can be used for diagnostic tests.”

In 2021, researchers from the University of H ouston and UT Southwestern Medical Center conducted a study which aimed to screen urine for possibly useful protein biomarkers of bladder cancer. The paper they authored was published in Oncotarget’s Volume 12, Issue 8, and entitled: “Urine protein biomarkers of bladder cancer arising from 16-plex antibody-based screens.”

“Urine biomarkers could potentially provide preliminary confirmation of low-grade BC [bladder cancer] before invasive procedures are performed and facilitate surveillance of BC, as reviewed [9].”

The Study

Patients may benefit in a number of different ways by using urine as fluid in diagnostic testing for bladder cancer. Urine is readily bioavailable, non-invasive, and it can also be collected and tested on a regular basis. Patients can even use various cost-effective point-of-care diagnostic tools, including at-home testing. First, the researchers assessed whether there were useful biomarkers of bladder cancer to be found in this fluid. The team used Luminex screening to test for both low and high levels of 16 proteins utilizing highly specific antibody-protein interactions.

“In this study, Luminex screening was used to simultaneously assay the protein abundances of 16 potential biomarkers in different stages of bladder cancer and then compared to urology clinic controls.”

ELISA validation was then used to determine which proteins were significantly elevated in bladder cancer. They found that levels of three urine proteins were capable of distinguishing between control and bladder cancer urine. One protein was also found to be capable of discriminating between high- and low-grade disease, and the successive clinical stages of bladder cancer.

“Upon ELISA validation, urine IL-1α, IL-1ra, and IL-8 were able to distinguish control urine from urine drawn from various bladder cancer stages, with IL-8 being the best discriminator.”

Conclusion

“These studies indicate that urine IL-1α, IL-1ra, and IL-8 are potential biomarkers of BC, two of which re-affirm previous reports.”

The researchers note that these newer urine biomarkers must be analyzed in larger cohorts, in specific clinical contexts, and compared to the performance of current diagnostic tools, such as the Bladderchek and UroVysion FISH assay.

“Looking forward, systematic studies in larger patient cohorts are warranted to establish the specific clinical contexts in which these markers may be used, including the following: (i) for initial diagnosis of BC, (ii) for surveillance of tumor recurrence, and/or (ii) for assessing treatment response following BCG therapy or other therapeutic modalities.”

Click here to read the full scientific study, published by Oncotarget.

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Trending with Impact: Composite Score May Further Classify HCC

May 7, 2021

In this trending study, the association between IGF/CTP composite scores, overall survival, and progression-free survival of hepatocellular carcinoma patients treated with sorafenib was investigated.

Human liver tissue under the microscope view.

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Sorafenib was the first systemic therapy approved to treat Child-Turcotte-Pugh (CTP) class A patients with advanced hepatocellular carcinoma (HCC). However, there are no biomarkers known to predict survival, treatment outcomes, or to guide this HCC systemic therapy. The insulin-like growth factor 1 Child-Turcotte-Pugh (IGF-1/CTP) composite score has emerged as a hepatic reserve assessment tool—and potential prognostic biomarker.

“Accurate assessment of the functional hepatic reserve is important to the prognostic and treatment prediction for patients with liver disease [1, 2].”

Researchers from the University of Texas MD Anderson Cancer Center, Massachusetts General Hospital, and Harvard Medical School conducted a study to assess the association of the IGF/CTP score with overall survival (OS) and progression-free survival (PFS) of HCC patients treated with sorafenib. Their paper was published in Oncotarget’s Volume 12, Issue 8 and entitled, “Insulin-like growth factor 1/Child-Turcotte-Pugh composite score as a predictor of treatment outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib.”

The Study

The majority of circulating insulin–like growth factor (IGF) is synthesized and secreted by the liver, and levels of IGF dramatically decrease in chronic liver disease and HCC. IGF can be a helpful tool to determine the prognosis of patients with advanced HCC while undergoing treatment with sorafenib. Researchers also use the Child-Turcotte-Pugh (CTP) qualitative scoring system to assess severity of liver cirrhosis, hepatic reserve, guide treatment decisions, and to stratify patients with HCC into three groups (A, B, and C). CTP class A has a better prognosis compared to classes B and C.

“Assessing liver reserve in HCC is of a great value as a tool for stratification of patients in clinical trials as well as to predict HCC outcome and guide therapy decisions in routine practice [28].”

In the researchers’ prospective study, 171 patients with HCC from the University of Texas MD Anderson Cancer Center were screened and included in this study. Of the patients, 116 were classified in CTP group A. Patient IGF/CTP scores were calculated and the researchers used the Kaplan-Meier method and log-rank test to estimate and compare the time-to-event outcomes between patient subgroups. Based on CTP and the IGF/CTP scores, researchers reclassified group A patients into AA and AB risk groups, which differed significantly in terms of OS and PFS. The researchers followed up with all patients in the study until disease progression or death. Unfortunately, during the follow-up period, 100 patients passed away.

“After IGF/CTP scoring, 87 of 116 CTP class A patients were reclassified as IGF/CTP-A (AA) and 29 patients were reclassified as IGF/CTP-B (AB) (Supplementary Table 1).”

Results & Conclusion

“Our study is the first prospective validation of the IGF/CTP scoring system association with the outcomes among patients with HCC treated with sorafenib.”

This study supported the researchers’ hypothesis that the IGF/CTP score is capable of further distinguishing and refining CTP class A patients. However, for CTP class A patients, due to limited power of the study, researchers were unable to meet the threshold for statistical significance for the OS and PFS durations of the reclassified groups AA and AB.

“Although our study was not powered to determine the predictive value of the IGF/CTP score in regard to median OS and PFS durations in CTP class A patients treated with sorafenib, our subset analyses of OS and PFS at different timepoints were statistically significant and, if independently validated, could change the standard approach to assessing hepatic reserve in patients with HCC.”

Click here to read the full scientific study, published by Oncotarget.

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Trending with Impact: Acute Myeloid Leukemia and Midostaurin Response

April 23, 2021

Researchers examined midostaurin resistance or sensitivity in a cohort of patients with acute myeloid leukemia.

Figure 2: Differential gene expression for midostaurin sensitive vs. resistant samples identifies a unique signature. — **Figure 2:** Differential gene expression for midostaurin sensitive vs. resistant samples identifies a unique signature.

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Acute myeloid leukemia (AML) is a heterogeneous malignancy that most commonly affects older adults, 60 years of age and older. NPM1, DNMT3A, and FLT3 are the most common genomic alterations found within this disease. In about 30% of AML patients, FLT3 is mutated. Midostaurin was the first FDA approved FLT3 inhibitor for AML. While Midostaurin has a successful overall survival benefit, both primary and secondary resistance remains common.

“A subtype of AML, classified by the presence of a FLT3-Internal Tandem Duplication (ITD) mutation, tends to have a worse prognosis with early relapse and death [5].”

Researchers from Oregon Health and Science University and Howard Hughes Medical Institute conducted a study to identify features that may predict response to midostaurin in FLT3 mutant and wild-type samples. They performed an ex vivo drug sensitivity screen on primary and relapsed AML samples, with corresponding targeted sequencing and RNA sequencing. The paper was entitled: “Genomic markers of midostaurin drug sensitivity in FLT3 mutated and FLT3 wild-type acute myeloid leukemia patients.”

The Study

In order to understand the impact that different genomic alterations have on midostaurin response, 214 patients were functionally assessed with midostaurin and their FLT3 status was annotated. Of these patients, the researcher identified 193 primary and 21 relapse AML samples from the Beat AML publicly available dataset. Risk groups within the cohort were as follows: 73 samples were favorable risk, 59 samples were intermediate, and 68 were adverse. The median age of patients in the cohort was 61, with 52% male and 48% female.

“We hypothesized that there are additional genomic alterations and gene expression changes outside of FLT3-ITD mutations that can influence AML sample resistance or sensitivity to midostaurin and aimed to further characterize these factors.”

Drug sensitivity screening, RNA sequencing/expression analysis, custom gene panel (GeneTrails) sequencing and variant detection, exome sequencing and variant detection, internal FLT3-ITD and NPM1 mutation detection, derivation of FLT3-ITD and NPM1 consensus calls, ex vivo functional drug screens, and statistical analysis were the methods used to observe the impact of genomic alterations on midostaurin response.

“Our research explored the multi-targeted nature of midostaurin and suggested a number of molecular mutational patterns that correlated with midostaurin drug sensitivity and resistance in both FLT3-ITD mutated and FLT3-ITD wild-type AML patient samples.”

Results

The researchers observed specific point mutations and gene expression patterns that they believe explain why there is a range of responses to midostaurin treatment. In the FLT3-ITD positive cohort, increased expression of the oncogene RGL4 (and regulator of the Ras-Raf-MEK-ERK cascade) correlated with poorer midostaurin response. In the FLT3-ITD negative cohort, KRAS mutations correlated with a poorer midostaurin response.

“We also observed that 16 / 34 of the most sensitive samples did not harbor a FLT3 mutation and a majority of differentially expressed genes were independent of FLT3 status.”

Conclusion

The authors point out that additional research studies will be needed given that their sample cohort was relatively small. They also note that since there are multiple FLT3 inhibitors available, it is important to understand the sensitivity mechanisms of each intervention in order to better personalize therapy for chemo-refractory or relapsed AML patients.

“Overall, we identify genomic alterations that correlate with midostaurin response independent of FLT3-ITD status, propose that Ras-Raf-MEK-ERK inhibition in combination therapy could limit resistance to midostaurin, and suggest that within the overall AML population there may be therapeutic benefit of midostaurin in patients with certain expression profiles.”

Click here to read the full scientific study, published in Oncotarget.

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Trending with Impact: The Vitamin D Binding Protein in Thyroid Cancer

April 8, 2021

Researchers compared vitamin D binding protein expression in papillary thyroid cancer tissues among Filipino American and European American patients.

3D rendered medically accurate illustration of thyroid cancer.

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On the basis of ethnicity, different gene variants of the vitamin D binding protein (DBP) are expressed among different populations of people around the world. Little is known about this highly polymorphic protein, though, researchers do know that DBP functions dependently and independently of vitamin D. Many previous research studies have examined the vitamin D-dependent correlation between DBP and cancer, however, few studies have examined DBP’s functionality independent of vitamin D, especially regarding the role of DBP expression in thyroid cancer.

“A systemic review demonstrated that a large number of chronic diseases, including cancers, have been associated with DBP variants [29].”

Filipino Americans are disproportionately affected by thyroid cancer, and researchers from Harbor-UCLA Medical Center, Loma Linda University School of Medicine, and Riverside University Health System conducted a study published in Oncotarget’s Volume 12, Issue #7, entitled, “Differential expression of Vitamin D binding protein in thyroid cancer health disparities.” The researchers compared the expression of DBP in thyroid cancer in Filipino and European Americans. The goal of this research was to further elucidate the functional implications of DBP in different stages of thyroid cancer across ethnicities.

“Although DBP is an essential protein with multifunctional properties, [28, 41–47], very few studies are available on its contribution to thyroid cancer oncogenesis.”

The Study

“Thyroid cancer incidence, recurrence, and death rates are higher among Filipino Americans than European Americans.”

To determine the correlation between differential DBP expression in tumor tissues and cancer staging among Filipino Americans and European Americans, the researchers gathered 200 archival papillary thyroid tissues; 100 from Filipino Americans and 100 from European Americans. They used immunohistochemistry to assay DBP expression in each sample and then analyzed the data with confocal microscopy.

“Since DBP gene variants showed differential expression across ethnicities [25, 40, 48, 49], DBP level in the tumor microenvironment may implicate the difference in TC [thyroid cancer] prognosis between Filipino and European Americans.”

First, the team evaluated whether or not there was any relationship between their DBP staining results and age, gender, or body mass index of the patients. They found no correlation between DBP levels and any of these variables, in either ethnicity. The researchers then analyzed the immunohistochemistry DBP staining results by ethnicity. They found moderate to strong intensity DBP staining across the European American cancer tissues and significantly low to no DBP staining in the Filipino American cancer tissues. The researchers also determined an inverse relationship between DBP expression and cancer stage—the lower the DBP expression, the poorer the prognosis.

“These data implied that DBP’s presence might play protective roles in cancer progression in European Americans compared to Filipino Americans, supporting the aggressive phenotype observed in Filipino Americans.”

Next, to observe the effects on cell migration and proliferation, DBP knockdown and overexpression (almost 90%) was achieved in the papillary thyroid tumor cells. The researchers demonstrated increased cancer cell proliferation and migration after the knockdown of the DBP gene. When the researchers overexpressed DBP, they observed a significant reduction in papillary thyroid cancer cell proliferation and migration.

Conclusion

“In conclusion, we demonstrate that the presence or absence of DBP inversely correlates to thyroid cancer staging in two ethnicities.”

The researchers note that while this study demonstrated low vitamin D binding protein expression in the advanced thyroid tumors of Filipino Americans, they acknowledge the need to determine the progressive loss of DBP throughout the stages of thyroid cancer.

“A future study is underway to determine the DBP regulation and its downstream pathways to elucidate strategies to eliminate the observed thyroid cancer health disparities.”

Click here to read the full scientific study, published in Oncotarget.

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Oncotarget Participating in Virtual AACR 2021 Annual Meeting

March 26, 2021

Oncotarget, exhibited by its publisher Impact Journals, will be participating virtually at the AACR Annual Meeting this year, from April 10-15 and May 17-21, 2021.

Oncotarget participating in the Annual AACR Meeting 2021 #AACR

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The American Association for Cancer Research (AACR) organizes an annual meeting program covering some of the most recent discoveries in cancer research. The conference aims to highlight work from the best minds in research and medicine from institutions all over the world. Oncotarget, exhibited by its publisher Impact Journals, will be participating virtually at the AACR Annual Meeting this year.

As of June 2020, Scopus released their latest 2019 Journal Rankings on Oncology. Oncotarget is among their highest rated (Q1) journals and ranked number one in total citations in oncology. The journal has published outstanding papers and reviews by authors including Bert Vogelstein, Peter K. Vogt, Pier Paolo Pandolfi, Arnold J. Levine, Brian Druker, and Carol Prives. Founding Oncotarget Editorial Board members include Nobel Laureates Andrew V. Schally and Gregg L. Semenza; Lasker Award recipients Alexander Varshavsky, Brian J. Druker, and Gregg L. Semenza; and 16 members of the US National Academy of Sciences. Oncotarget is indexed and archived in PubMed, PubMed Central, Scopus, EMBASE, and META (Chan Zuckerberg Initiative) .

The 2021 AACR conference, a two-week online event, will take place from April 10-15 and May 17-21, 2021. Topics include population science and prevention, cancer biology, translational and clinical studies, survivorship, and advocacy.

In 2019, Oncotarget participated in the AACR Annual Meeting at the Georgia World Congress Center in Atlanta, Georgia, USA, and “AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics,” at the Hynes Convention Center in Boston, Massachusetts, USA. The total registration count from the 2019 AACR Annual Meeting was over 21,000—nearly 16,000 of which were scientific attendees from all over the world. Click here to view photos from Oncotarget’s participation in the 2019 AACR Annual Meeting.

Follow the Oncotarget Twitter account (@Oncotarget) for live updates about the conference using the #AACR21 hashtag.

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Trending with Impact: Hepatocellular Carcinoma in The Andes Mountains

March 11, 2021

Young people living in the Andes Mountains are disproportionately affected by hepatocellular carcinoma compared to other youth around the world. Researchers conducted a study to better understand the cause.

Peru. View of the Urubamba River through the Aguascalientes Village.

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Andean people live in sparsely populated regions in the Andes Mountains of South America. It is the longest mountain range in the world; spanning seven countries from southern Peru to southern Argentina. Due to the high elevations (averaging 13,000 feet; peaking at 22,834 feet), these areas are known for such low oxygen levels that Andean people have adapted physiologically to the extreme conditions.

Around the world, hepatocellular carcinoma (HCC) is the main form of primary liver cancer and commonly affects older patients after they have had prolonged liver disease. However, among Andean people, half of the total patients who develop HCC are adolescents and young adults. Researchers—from Sorbonne Université, Institut Pasteur, Université de Rennes, and Université de Toulouse in France, and the Instituto Nacional de Enfermedades Neoplásicas in Peru—conducted a study to better understand HCC in Andean people.

“To deepen our understanding of the molecular determinants of the disease in this population, we conducted an integrative analysis of gene expression and DNA methylation in HCC developed by 74 Peruvian patients, including 39 adolescents and young adults.”

The Study

“The 74 Peruvian patients with HCC included in the present study carried mitochondrial DNA (mtDNA) haplotypes of the four ancestral lineages (A–D) shared by Indigenous American populations (Figure 1A and Table 1) [23].”

The researchers retrospectively conducted transcriptome profiling of patient samples from 74 Peruvian patients with HCC. They compared gene expression data (after batch-effect removal) and found that Peruvian HCC is characterized as a distinct molecular subtype. This, now referred to as the “Amerind signature,” identifies Peruvian HCC as a distinct phenotypic cluster.

“A 961 gene signature was defined (hereinafter referred to as “Amerind signature”), of which 806 were upregulated and 155 downregulated in Peruvian HCC (Figure 3A and Supplementary Table 4).”

Methylome profiling was also conducted by the researchers to show the dynamics of DNA methylation marks, which revealed that Peruvian HCC is associated with a genome-wide hypermethylation pattern. They explain that DNA hydroxymethylation also represents a relevant epigenetic mark in Peruvian HCC. In addition, the researchers found evidence that Peruvian HCC tumor cells have a weaker retinoid signaling signature, which opens the door to potential therapeutic targets.

“The genomic analysis of Peruvian HCC evidenced a weaker retinoid signaling signature in tumor cells, which could pinpoint novel targets and drugs for anticancer targeted therapy (Figure 1C and Supplementary Table 1) [45]. We hypothesized that this weaker retinoid signaling could be responsible for the increased proliferation; hence, the pharmacological response to RA should antagonize this process.”

Conclusion

After comparing this sample of patients with Peruvian HCC with other HCC tumors from other countries around the world, molecular divergence in Peruvian HCC was demonstrated by showing “hierarchical clustering relying on a large and meaningful gene expression signature.” The researchers do not yet know if these differences are due to external/geographic or genomic factors.

“Whether this molecular phenotype is due to anthropological specificities embedded in genome architecture, to extrinsic etiological cues, or to subtle interplays between both components remains to be ascertained.”

With this being said, the researchers believe that this study stresses the need to carefully consider the potentially prominent roles of human genomic architecture and biogeography when it comes to cancer and underreported minorities and Indigenous patients, especially in low- and middle-income countries. They are forthcoming about limitations in their study and mention having analyzed a fairly small sized cohort. Importantly, the findings from this study create a case for developing therapeutics that are tailored to this new molecular subtype of HCC.

“The present study establishes a foundation for the dissection of the functional importance of RA-mediated epigenetic control in HCC and therapeutics tailored to patients with Indigenous American ancestry.”

Click here to read the full scientific study, published in Oncotarget.

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Trending with Impact: Murine Model of Cancer-derived Myocardial Damage

February 18, 2021

Researchers in this study employed one of the few available murine cachexia models and validated its ability to be used in future studies of cancer-derived myocardial damage.

Part of Figure 2: Alterations in the myocardium of CT26-inoculated BALB/c mice.

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Cachexia, a complex metabolic syndrome characterized in part by the loss of muscle mass, can account for up to 30% of all cancer-related deaths. Myocardial atrophy, or cardiac remodeling/degradation, is a phenotype of cachexia and a common cause of death.

“The causes of cancer-derived myocardial impairment might be the effects of cancer itself, background heart disease, and influence of cancer treatments; however, they have not been given much clinical importance, and specific treatment efforts are delayed [8].”

Researchers from Nara Medical University, Hanna Central Hospital, and Hoshida Minami Hospital in Nara and Osaka, Japan, and Nantong University in Jiangsu Province, China, note that while myocardial damage in cancer patients is known to be a cause of death, there are few murine cachexia models available to evaluate cancer-derived heart disorders. Thus, there is a need for further studies that may allow researchers to establish an intervention to prevent myocardial damage in cancer patients.

“In this study, we used the mouse cancer cachexia model that we previously established [14] to examine the status of cancer-derived myocardial impairment reported in literature, and validate our model for studying cancer-derived myocardial impairment.”

The Study

Some causes of cancer-derived myocardial impairment have been reported as cancer-induced cytokines, oxidative stress, depletion of antioxidants, and protein catabolism as a result of AKT/mTOR inhibition.

“Despite these advances in our understanding, the multifactorial mechanisms underlying cancer-derived myocardial impairment remain incompletely understood, necessitating further investigations to elucidate the molecular mechanisms and prevent myocardial damage in cancer patients.”

The researchers previously established a mouse cancer cachexia model. In this study, they aimed to validate their model by employing it in the examination of cancer-derived myocardial impairment that has been reported in previous literature. Their study enlisted the mouse model, CT26 colon cancer cell cultures, protein extraction, histological analysis, immunoblot analysis, enzyme-linked immunosorbent assay (ELISA), mitochondrial stress tests (Seahorse assay), glycolytic stress tests, and statistical analysis.

Conclusion

“In summary, our established mouse cachexia model showed various myocardial changes associated with cancer cachexia such as oxidative stress in the myocardium, energy metabolism, autophagy, and inflammatory cytokines.”

Results obtained by the researchers in this study using their mouse cachexia model are congruent with previously reported results about cancerous myocardial damage, and therefore provide reasonable evidence that it may be used in future studies.

“The established mouse cachexia model can therefore be considered useful for analyzing cancer-derived myocardial damage.”

Click here to read the full scientific study, published in Oncotarget.

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An Overview of Cannabis and Cancer

February 9, 2021

Researchers review different varieties of cannabinoids, the signaling pathways they affect, and their role in different types of cancer.

Close up of female Cannabis flower with a high production of cannabinoid resin

The Top-Performer series highlights research literature published in Oncotarget that has generated a high Altmetric score. Altmetric scores, located at the top-left of trending Oncotarget papers, provide an at-a-glance indication of the volume and type of online attention the research has received. Read Oncotarget’s Top 100 Altmetric papers.

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In a high-rated paper published in 2014 in Oncotarget, researchers from India’s Sanjay Gandhi Post Graduate Institute of Medical Sciences and the United States’ Ohio State University reviewed cannabinoids, their role in different types of cancer, and the signaling pathways they affect. Today, this paper currently presents with an Altmetric Attention score of 200.

“In this review article, we will focus on a broad range of cannabinoids, their receptor dependent and receptor independent functional roles against various cancer types with respect to growth, metastasis, energy metabolism, immune environment, stemness and future perspectives in exploring new possible therapeutic opportunities.”

Cannabinoids and Receptors

“[The] Cannabis sativa plant has been used for several hundreds of years both recreationally and medicinally.”

Researchers trace the earliest archaeological evidence of cannabis medical use back to ancient China, during the Han Dynasty. The use of this plant was recommended for rheumatic pain, constipation, disorders of the female reproductive tract, and malaria, among other conditions. Cannabis sativa contains three major classes of bioactive molecules; flavonoids, terpenoids, and 100+ types of cannabinoids.

Cannabinoids are a family of complex chemicals that activate and bind to two receptors in mammals named central cannabinoid receptor one (CB1) and peripheral cannabinoid receptor two (CB2). These receptors are found abundantly throughout the central nervous system and immune system.

“CB1/2 receptors are also responsible for proliferation, motility, invasion, adhesion and apoptosis of cancer cells both in vitro and in vivo.”

CB1 and CB2 receptors have been used as targets for the treatment of various diseases, including neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease, neuropathic and inflammatory pain, glaucoma, multiple sclerosis, cardiovascular disorders, obesity, and more. Today, in addition to inhibiting nausea and emesis, stimulating appetite, improving mood, and relieving pain and insomnia that cancer patients face, cannabinoids used in the targeted killing of tumor cells has been a major discovery in cancer treatment.

“In this review article we focused on the role of cannabinoids in different cancer types and the respective signaling pathways.”

Endocannabinoids

“Endogenous cannabinoids which are produced in our body include lipid molecules containing long-chain polyunsaturated fatty acids, amides, esters and ethers that bind to CB1 or CB2 receptors.”

Endocannabinoids act primarily as neuromodulators, or reverse messengers, which can affect the release of neurotransmitters. They also play important role in regulating inflammation, insulin, and fat and energy metabolism, which affects our mood, appetite, pain sensation, inflammation response, and memory.

Phytocannabinoids

“Phytocannabinoids are only known to occur naturally in significant quantities in the cannabis plant, and are concentrated in a viscous resin that is produced in glandular structures known as trichomes.”

Over 120 phytocannabinoids are capable of interacting within the body’s own biological systems because their structures and behaviors mimic those of endocannabinoids (cannabinoids that are synthesized by our own bodies). The most prevalent natural cannabinoids are delta-9-tetrahydrocannabinol (∆9-THC), cannabidiol (CBD), and cannabinol (CBN).

Synthetic Cannabinoids

“Synthetic cannabinoids are classified on the basis of chemical structure of molecules and they are capable of a more selective activation of cannabinoid receptors [28].”

The researchers explain that synthetic cannabinoids have been used extensively in pharmacology to gain better insight about their action in order to evaluate the potential use of cannabinoids clinically.

Within the synthetic category, classical cannabinoids are compounds isolated from the Cannabis sativa plant or its synthetic analogs. Nonclassical cannabinoids “are a family of AC-bicyclic and ACD-tricyclic cannabinoid analogs.” Aminoalkylindoles are non-cannabinoid molecules given cannabis-mimicking capabilities. Eicosanoids are compounds that can enhance or inhibit physiological and pathophysiological responses. These lipid mediators also have an affinity for CB1 and CB2 receptors.

Cannabinoids in Cancer

Multiple studies have shown that THC, CBD, and synthetic cannabinoids can inhibit breast cancer cell proliferation and drive them toward apoptosis.

“It [breast cancer] is classified into three main subtypes according to their molecular profiles: hormone receptor-positive, HER2-positive (ErbB2-positive, a member of EGFR family) and triple-negative tumors [42-43]. Cannabinoid-based medicines have been useful for the treatment of these three breast cancer subtypes.”

In prostate cancer, CB1 and CB2 expression levels are often higher in prostate cancer tissues and several cell lines compared to normal prostate epithelial cells. Studies have found that cannabinoids have either induced cell death or activated pathways that lead to growth inhibition and increased patient survival.

Preclinical cancer models have shown that cannabinoids can alter gene expression, block enzymes, inhibit signaling pathways, and induce apoptosis in mice with lung cancer. In skin and pancreatic cancers, researchers have found that the activation of CB1/2 receptors induced the apoptotic death of tumorigenic cells, without affecting the normal cells. In bone cancer studies, researchers found that cannabinoids reduced pain and bone loss in mice.

“Cannabinoids could halt tumor development without side effects via specific targeting of CB1/CB2 receptor.”

Cannabinoids have anti-tumorigenic properties in glioma, lymphoma, oral cancers, and thyroid carcinoma. In young people, marijuana smoking has been found to increase the incidence of head and neck cancer, however, cannabinoids have anti-tumor properties.

Conclusion

“Cannabinoids exert a direct anti-proliferative effect on tumors of different origin.”

Given that cannabinoid receptors are often demonstrated to be expressed higher in tumor cells than in normal cells, cannabinoids are more specific to cancer cells than to normal cells. The researchers conclude their review by noting that it is important to identify which cannabinoids are most compatible with an individual cancer or disorder to have the greatest impact on patient outcome.

“It is important to understand which of the cannabinoid receptors are expressed and activated in different tumors as each receptor follows a different signaling mechanism.”

Years after this paper was published, subsequent studies have confirmed and expanded on many ideas mentioned in this review, including the regenerative and pharmacological effects of THC, synthetic cannabis used to treat thrombosis, increased expression of CB2 potentially linked to colon cancer, experiments with cannabis extracts, synergistic combinations of cannabinoids, and much more.

Click here to read the full scientific review, published in Oncotarget.

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Special Collection by Oncotarget: Lung Cancer

December 11, 2020

Oncotarget Special Collection: Lung Cancer

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Lung cancer is still the leading cause of cancer-related mortality worldwide. According to the CDC, smoking cigarettes is linked to 80-90% of lung cancer deaths in the United States. In non-smokers, lung cancer can be caused by exposure to radon, secondhand smoke, air pollution, asbestos, diesel exhaust, and other chemicals and factors.

Some symptoms of lung cancer include pain in chest or ribs, frequent respiratory infections, shortness of breath, wheezing, fatigue or loss of appetite. As numerous research studies about lung cancer are currently underway, we hope this Special Collection will set future research in motion to discover more causes and treatments for this disease.

Special Collections: Lung Cancer

Oncotarget publishes open access peer-reviewed literature about research studies, clinical studies, reviews, case reports, and meta-analyses on a variety of different topics pertaining to cancer. Lung cancer continues to be an area of interest for researchers, therefore, the Special Collection on Lung Cancer was created by Oncotarget for scientists and researchers to discover new biomarkers, mechanisms, and therapies to treat this cancer.

All content submitted for publication has been reviewed by a diligent board of academic editors and world-renowned scientists and researchers. In this Special Collection, the content focussing on lung cancer is organized together in one place, including papers such as “Molecular pathways and therapeutic targets in lung cancer” by Emma Shtivelman, Thomas Hensing, George R. Simon, Phillip A. Dennis, Gregory A. Otterson, Raphael Bueno, and Ravi Salgia. This review is a summary of the pathways and mechanisms involved in current treatment methods for lung cancer of various types.

This meta-analysis examines the relationship between exposure to PM2.5 (particulate matter or fine particles) and lung cancer incidence and mortality: “Relationship between exposure to PM2.5 and lung cancer incidence and mortality: A meta-analysis” by Feifei Huang, Bing Pan, Jun Wu, Engeng Chen, and Liying Chen.

This review focuses on improved anticancer agents and therapy options for lung cancer patients with acquired EGFR TKI (chemotherapy) resistance: “Clinical strategies for acquired epidermal growth factor receptor tyrosine kinase inhibitor resistance in non-small-cell lung cancer patients” by Lijun Dong, Dan Lei, and Haijun Zhang.

Read more about lung cancer on Oncotarget.com.

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Oncotarget is a unique platform designed to house scientific studies in a journal format that is available for anyone to read—without a paywall making access more difficult. This means information that has the potential to benefit our societies from the inside out can be shared with friends, neighbors, colleagues and other researchers, far and wide.

Mikhail Blagosklonny

Oncotarget Launches New Special Collection on Breast Cancer

December 4, 2020

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By Kathryn Atkins

As you may know, Oncotarget is a scientific journal that publishes oncology-focused review and research papers every week on its open access platform — available at no cost to readers. Recently, a new Special Collections series debuted, and the first collection launched in honor of breast cancer awareness.

What makes our collections special?

Oncotarget carefully selects the most credible and insightful studies to publish on Oncotarget.com, while also choosing papers that link different fields of oncology, cancer research, and biomedical sciences together to eliminate borders between specialties. The term “oncotarget” encompasses all molecules, pathways, cellular functions, cell types, and tissues that can be viewed as targets relevant to cancer, as well as other diseases. This journal is a resource for oncology researchers and the larger scientific community.

Before a study is published in Oncotarget, selected papers are meticulously peer-reviewed by an editorial board of award-winning scientific editors from academic universities and institutions well-known for their excellence and precision. Click here for a complete list of Oncotarget Editorial Board members.

Breast cancer research

Each year, over 40,000 women and men lose the fight against breast cancer in the United States. After skin cancer, breast cancer is the most commonly diagnosed cancer in women. The spread of breast cancer awareness and increase in research funding has helped develop advances and discoveries in the diagnosis and treatment of this proliferous cancer.

The new Special Collections by Oncotarget are yet another tool researchers and science readers alike may use as a resource to learn more about breast cancer. The creators of these collections also hope that they may be used by scientists to discover new biomarkers, mechanisms, and therapies to improve our quality of life and better treat cancer and diseases.

Click here to explore the Special Collection on breast cancer.