Meet our Clinical Research Alumni and Mentors

Q&A Event – Ask your Questions!

Ask all your questions regarding clinical research, monitoring, clinical studies, clinical trials

and career opportunities to Dr Anna Leonov, Clinical Operations Specialist in Syneos Health.

Speaker: Dr Anna Leonov, Clinical Operations Specialist at Syneos Health

Time: Saturday, Sept. 10, 2022, from 11:00 AM EST

FREE event by Zoom: https://www.eventbrite.ca/e/406278358507

Book a seat now. Log-in details for Zoom will be emailed on Friday, September 9th.

For more information about the CRA-School services click https://bit.ly/3veWxDe or here

Vishwambari T, MBBS, CCRP. Medical Advisor

Tumorigenesis is fueled by the altered metabolic pathways of necessary nutrients like carbohydrates, lipids and amino acids. These alterations are facilitated not only by carcinogenic proteins, but by non-coding RNAs, among which Circular_RNA (circRNA) has become in the recent years the focus of attention.

CircRNA plays an important role in regulating cellular metabolism through binding with corresponding mRNAs or proteins directly.

We are reviewing the emergent findings and circRNAs contribution to cancer glycolysis and oxidative phosphorylation  to understand the cancer metabolic regulatory system. We will also see how circRNA, owing to their unique structure and influence via exosomes and cancer stem cells, may help improving clinical cancer treatment by targeting cancer metabolism.

Background

Deregulated metabolism is a hallmark feature in tumors caused due to genome instability. It is the most important factor in growth and division of cancer cells and hence tumor progression.

The most prominent cancer-associated metabolic changes include the deregulated uptake of glucose and amino acids, use of opportunistic modes of nutrient acquisition, use of glycolysis / tricarboxylic acid cycle (TCA), cycle intermediates for biosynthesis, nicotinamide adenine dinucleotide phosphate (NADPH) production, and increased demand for nitrogen. Research dedicated to studying the underlying abnormal metabolism in cancer is of pivotal importance.

Circular RNA (or circRNA) is a type of single-stranded RNA formed by ‘back-splicing’ of a linear chimeric RNA, it is known to form a covalently closed continuous loop, where the 3′ and 5′ ends, normally present in an RNA, have been joined together. Their circular structure makes them stable in cells and body fluids and resistant to exonuclease digestion, so they have much longer half-life than their parental mRNAs (48 h vs. 10 h). This feature confers numerous properties to circular RNA, many of which have only recently been identified, like its affect on cell growth, cell migration, and its invasion of tumorigenesis. CircRNAs secreted within exosomes are potential cancer biomarkers.

Circular RNAs have a tissue-restricted and cancer-specific expression pattern, and the data collected suggest that these molecules have potential to directly regulate transcription by interacting with mRNAs or long non-coding RNAs (lncRNAs), sponging mRNAs, or RNA binding proteins (RBPs). Some circRNAs can even be translated into proteins.

The aim of this review is to explore the relationship between circRNAs and cancer metabolism to provide a better theoretical basis for clinical diagnosis and treatment of cancers by reviewing information on how circRNAs affect metabolism of carbohydrate, lipid, and amino acids.

CircRNAs in metabolism of Glucose

Cancer cells proliferate by modifying the metabolism of glucose. In norm in aerobic conditions, cells use glucose to generate ATP through oxidative phosphorylation and resort to glycolysis in anaerobic or anoxic conditions. Cancer cells however undergo glycolysis even in normoxic conditions. This is called “the Warburg effect” and it is instrumental in malignancy of cancer cells, as proposed in the 1920s , by Otto Warburg.

This effect alleviates damage due to oxidative stress caused by mitochondria when cancer cells choose glycolysis instead of OXPHOS to generate energy. This is followed by production of excess of lactic acid by the Warburg effect which aids to circumvent the immune surveillance.

The enhanced intracellular transport of glucose in tumor cells, maintains a high-speed glycolysis process and a high level of ATP/ADP ratio. It is hypothesized that the Warburg effect consumes an enormous amount of glucose to either produce excess amount of lactic acid creating a hyperacid microenvironment, or it starves healthy cells in the vicinity of the tumor. The excess amount of lactate produced may also stimulate neo vascularisation via the HIF1-α_.. The table below illustrates the effects of circRNAs on aerobic glycolysis of all these levels, circRNAs play a vital role in glycolysis by regulating transporters and enzymes

circRNAs in glycolysis

Table 1:

From: CircRNAs in cancer metabolism: a review

Previous studies have shown that the Warburg effect may be regulated by oncogenes, tumor suppressor genes, and key enzymes in glucose metabolism, but the underlying mechanisms are incomplete. Pieces of evidence show that circRNA is an emerging regulatory factor of the Warburg effect.

CircRNAs in Regulating Transporters of Glycolysis

In the major energy providing pathway, the carbohydrate metabolism pathway involves the participation of a group of metabolic enzymes. The process of glycolysis starts when glucose transporter (GLUT) transports extracellular glucose into the cell. To meet the excessive requirements of glucose, GLUTs ranging from GLUT1 to GLUT4 are all over-expressed in tumor cells.

Studies have shown that certain circRNAs are significantly up-regulated in the  tumor tissues, which in turn promotes tumor glycolysis, growth, and metastasis by affecting the cell metabolism. The suppression of circHIPK3 in pancreatic islets can reduce the expression of Slc2a2, which encodes GLUT2. CircHIPK3 reduces the expression levels of transporters as well as enzymes, and inhibits glycolysis by targeting miR-124. Circ-Amotl1 can target AKT1 and PDK1.

The down-regulated circARHGAP10 in non-small cell lung cancer(NSCLC) can decrease the expression of GLUT1, which inhibits intracellular transport of glucose, glucose consumption as well as lactate formation this consecutively inhibits glycolysis by sponging miR-150-5p. In NSCLC, hsa_circ_0002130 targets miR-498 to up-regulate GLUT1, hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), regulating the glycolysis and eventually progresses NSCLC by increasing the resistance towards Osimertinib.

In colorectal cancer (CRC), the absorption of miR760, regulation of GLUT1, and stimulation of glycolysis, growth, as well as metastasis of cells. is directly influenced by the up-regulated circDENND4C. On the other hand, down-regulation of circDENND4C can inhibit glycolysis in CRC cells, and overexpression of GLUT1 can remedy this inhibition.

In oral squamous cell carcinoma (OSCC), the expression of circRNA_100290 cells was significantly up-regulated. GLUT1 was up-regulated through miR-378a to promote glycolysis, growth, and metastasis of cells.

 CircRNAs in Regulating Enzymes or Kinases of Glycolysis

CircRNAs also effect the enzymes of glucose metabolism. Another circRNA called circ-Amotl1 was reported to be able to physically bind to PDK1 and AKT1 and translocate them into the nucleus, which antagonizes apoptosis. Three speed-limiting enzymes including hexokinase (HK), 6-phosphfructa-1-kinase (PFK), and pyruvate kinase (PK) work together to transform glucose into pyruvate. Lactate dehydrogenase A (LDHA), which is the final enzyme in aerobic glycolysis, catalyses pyruvate to lactate.

Recent studies report that in the production of lactic acid from pyruvate, some circRNAs are able to influence the glycolysis by targeting ENO1, PKM2, and LDHA. Eventually, the monocarboxylate transporter (MCT) releases this lactate into the extracellular matrix. In addition to this, pyruvate dehydrogenase kinase (PDK) blocks the traditional OXPHOS by neutralising pyruvate dehydrogenase (PDH) which catalyses pyruvate into acetyl-COA.

PDK1 is a component of the PI3K/AKT pathway to affect cell growth, differentiation, and survival. AKT1, as a protein kinase signaling pathway known to trigger cancer, regulates the expression of  transcription factors (TFs) and affects cellular glycolysis by activating downstream cell growth regulators.

Some experimental studies have shown that suppressing circHIPK3, which is abundant in pancreatic islets, decreased Slc2a2 expression that encodes GLUT2. CircHIPK3 could sponge miR-124, which represses the expression of several enzymes and transporters of glycolysis. CircRNA circ-Amotl1 is capable of physically binding to PDK1 and AKT1 and translocate them into the nucleus, which antagonises apoptosis. These circRNAs are likely to induce the Warburg effect in tumor tissues.

ENO1

Enolase 1 (ENO1), plays an important regulatory role in the Warburg effect of tumor cells.

Circ-ENO1 can increase the expression of ENO1 in Lung Adenocarcinoma (LUAD) by targeting miR-22-3p and the suppression of circ-ENO1 reduces the activity of ENO1, delay the uptake of glucose and formation of lactic acid, and eventually inhibit cell glycolysis. Reduced ATP levels, EMT, inhibition of cell growth, cell migration, and apoptosis are induced by down-regulated circ-ENO1.

PKM2

Pyruvate kinase (PK) is a crucial enzyme in both normal glycolysis as well as in abnormal glycolysis during tumorigenesis. PK plays a crucial role in the final step of glycolysis where it catalyses the conversion of phosphoric acid by phosphoenolpyruvate and ADP to ATP.

There are 4 isozymes of pyruvate kinase namely-PKXL, PKR, PKM1 AND PKM2, each of these are expressed during gluconeogenesis in different organs. PKM2 which is expressed in the embryonic cells, stem cells, and tumor cells with active nucleic acid syntheses.

PKM2 also has a vital role in cancer growth and carbohydrate metabolism in tumor cells. PKM2 exists in two isomeric forms: a highly active tetramer and a low-activity or restrictive dimer. The dimeric form promotes the anabolism of carbohydrates, and the tetrameric form aids in OXPHOS of glucose and provides energy for cells. In tumor cells the overexpression of PKM2 and the transformation between the two forms aids the tumor cells survival in various environments.

In Colorectal Carcinoma (CRC), hsa_circ_0005963 (ciRS-122) exosomes are transported from oxaliplatin-resistant cells to sensitive cells. the reduced ciRS-122, targets miR-122 and up-regulates the expression of PKM2 in oxaliplatin-resistant cells, which boosts aerobic glycolysis, ATP production, and the development of CRC.

LDHA

Lactate dehydrogenase A (LDH-A) executes the last step of aerobic glycolysis and catalyses the inter-conversion of pyruvate and L-lactate. In bladder cancer (BC) the prognosis is poor when, in cells experiencing hypoxic environment, aerobic glycolysis is promoted by the up-regulated has_circRNA_403658, which primarily regulates the expression of LDHA. The excess production of has_circRNA_403658 in triggered by excess of HIF1 and is encoded by its host gene ZNF292. Similarly when the production of has_circRNA_403658 was stifled there was a significant down regulation of LDHA leading to reduced LDH activity, lactate production, glucose absorption, along with ATP production.

Transcription factors, Genes, and Signaling Pathways of Glycolysis

CircRNA is a member of the ncRNAs and has an important role in monitoring the expression of mutation of Transcription factors (TF) and their regulatory function. The circRNA achieves this by targeting the HIF-1, C-myc, CUX1, p53, FLOT2, RAS, and STAT3, which are the TF of miRNAs, there by eventually modulating the miRNAs. These TFs also have impact on the Warburg effect.

Signaling Pathways of Glycolysis

Fig 1: Relationships between circRNAs and TFs

HIF-1

The Warburg effect is directly proportional to the hypoxia in the cell. Activation of oncogenes in hypoxic solid tumor cells result in transcription of genes and enzymes like HK, PKM, MCT4 abd Hypoxia-inducible_factor HIF-1, which encourages glycolysis instead of OXPHOS. This increases the production of lactate proportional to the level of HIF-1 by up-regulating PDK1

In  breast cancer cells, HIF-1α can up-regulate circDENND4C. This can target the miR-200b and miR-200c, which eventually down-regulates LDHA and Sirtiuin 2. This inhibits tumor glycolysis, and insistently promotes cell proliferation in a hypoxic environment. In human umbilical cord vascular endothelial cells (HUVEC), circ_0010729 is over expressed along with HIF-1, especially in hypoxia-induced HUVEC.

By sponging miR-186, this over-expressed circ_0010729 promotes glycolysis and cell growth, and up-regulating HIF-1α. This causes increased glucose supply to the tumor cells with the support of new vessels. Hence, it can be said that  circ_0010729 facilitates glycolysis by accelerating the development of vascular endothelial cells

C-Myc

C-Myc is one of the most crucial oncogenic TFs. It regulates cell metabolism and can also activate the Warburg effect. The collaboration between C-Myc and over expressed HIF-1 is known to raise the levels of  glycolytic components GLUT1, HK2, and PDK1. C-myc is an oncogene, which can be regulated by several circRNAs.

In CRC, miR-145 is targeted by both circRNA_001569 and circBIRC6. Certain circRNA have the ability to target more than one miRNAs like circBIRC6 also targets miR-34a along with miR-145. miR-34a has the ability to inhibit c-myc oncogene. Circ-Amotl1 can also supress the nuclear translocation mutation of c-myc, and also influence the STAT3 and AKT which in turn promotes tumor development through enhanced aerobic glycolysis and not by using endogenous RNA (ceRNA).

Interestingly, a protein FBXW7-185aa which is capable of interacting with de-ubiquitinating enzyme USP28, could be encoded by circ-FBXW7. This circ-FBXW7-185aa, could possibly indirectly degrade c-myc thereby ameliorating the Warburg Effect.

P53

The tumor suppressor gene P53 is an important TF which can regulate tumor metabolism along with HIF-1 and C-Myc oncogene, as a tumor suppressor gene. P53 helps circRNA in regulating metabolism. In triple negative breast cancer (TNBC), research has shown that circSEPT9 has the ability to  regulate the expression of Leukemia Inhibitory Factor (LIF) via sponging miR-637 and activate LIF/Stat3 signaling pathway involved in progression of TNBC. The elevated levels of circSEPT9 which was found in TNBC tissues, is and indicator of poor prognosis due to advanced clinical stage.

On the other hand, suppression of circSEPT9 in TNBC cells reduced proliferation, migration and invasion of cells, stimulated apoptosis and autophagocytosis in TNBC cells, as well as inhibited tumor growth and metastasis in vivo. It can be concluded that, the potential of circSEPT9 as a prognostic marker and therapeutical target for TNBC is worthy of further research.

Regulation of signaling pathways

The effects of circRNAs

Fig 2: The effects of circRNAs on the Warburg effect-associated signaling pathways. This figure indicates the effects of circRNAs on the Warburg effect-associated signaling pathways. It shows how circRNAs interact with these metabolic pathways by enzymes and transporters associated with the Warburg effect.

The majority of circRNAs can antagonize microRNAs to indirectly produce effects. HIF1-α regulates GLUT, HK2, PDK, LDHA. The PI3K/Akt pathway promotes glucose GLUT, HK2, PFK2, pyruvate kinase M2 (PKM2), and PDK. The change of RAS pathway up-regulated HK2. P53 up-regulated GLUT, HK2. The STAT3 pathway promotes HK2. Wnt/β-catenin pathway up-regulates PDK transcription while promoting c-myc. The positive relationships are shown by arrows, and the negative relationships are shown by short dashes.

The collective work of all TFs forms a network, which consists of various signalling pathways involving diverse circRNAs. This regulatory pathway is known to affect the Warburg effect.

PI3K/Akt

PI3K/Akt pathway is vital in glycogenesis and promoting glucose uptake. Glycogenesis is stimulated by HK2 and PFK2 under the influence of Akt (Protein_kinase_B).  PI3K/Akt signaling pathway, affects the absorption of glucose and glycogenesis by increasing the antioxidant activity of HIF-1α along with the elevated levels of HK2 and PFK2. Down streaming of Akt1 is brought about by MTOR complex1, which can phosphorylate elf4E-binding proteins and support HIF-1α to promote GLUT1, HK2, and PFK2.

In Hirschsprung disease, he levels of Akt# and circ-ZNF609 are elevated, while the level of miR-150-5p expression is reduced. It can be said circ-ZNF609 might support AKT3 by targeting miR-150-5p which improves the Warburg effect. More research is required to confirm its role in cancer metabolism.

RAS

The KRAS gene provides instructions for making a protein called K-Ras (Kirsten rat sarcoma virus) that is part of a signaling pathway known as the RAS/MAPK pathway. The KRAS belongs to a class of genes known as oncogenes. These proteins play important roles in cell division, cell differentiation, and apoptosis. When mutated, they become cancerous, especially in colorectal cancer, non-small cell lung cancer, and prostrate cancer. Mutated KRAS upregulates the GLUT1 , and glycolytic enzymes thereby contributing to the Warburg effect in cancer cells.

STAT3

The Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor which in humans is encoded by the STAT3 gene. STAT3 is studied to be very important in the development, progression, and maintenance of many human tumors, validating STAT3 as an anticancer target. The STAT3 pathway promotes inflammatory environment, cell proliferation which favors cancer development under the stimulation by circ-Amotl1.

In osteosarcoma, miR-449a mediates the STAT3 pathway indirectly with the aid of hsa_circ_0009910. This hsa_circ_0009910 can have a sponging effect on miR-449a which antagonises IL6R.

Wnt/β-catenin

Wnts are glycoproteins which act as ligands in stimulating receptor-mediated signal transduction pathways, which modulate cell proliferation, survival, and cell behavior. Upregulating the transcription of MCT1 and PKD1 is how the Wnt/β-catenin pathway regulates the Warburg effect.

In NSCLC cells, the circCDR1as/miR-219a-5p/SOX5 axis may target the Wnt/β-catenin pathway and regulate the Warburg effect. In nasopharyngeal carcinoma (NPC), circCDR1 targets the miR-7-5p, upregulates E2F3, which increases the glucose consumption and production of lactic acid.

In contrast, suppression of circCDR1as, triggers the  Wnt/β-catenin pathway to significantly inhibit the metabolism of HK1 and HONE1 cells (NPC line).¹⁰⁵

All in all, circRNAs that regulate tumor cell metabolism of lung adenocarcinoma and nasopharyngeal carcinoma are closely related to the Wnt/β-catenin pathway.

Conclusion

In depth research in the field of circRNA has brought forward a lot of new understandings about cancer glucose metabolism. Evidence that Warburg effect may be triggered by the rogue circRNAs, which may contribute to development of various malignancies by impacting various metabolic pathways in cancer.

There are studies showing evidence of close association between circRNA and carbohydrate, lipid, and amino acid metabolisms. Glucose metabolism is a topic of review herein, where the molecular mechanism involves circRNA in tumor glycolysis by regulating transporters, enzymes, kinases, TFs, genes, and glycolysis signaling pathways (Figure 2) was reviewed.

It is worth investing further how the abnormally expressed circulation circRNAs participate in cancer glucose metabolism, as they are substantially related to various cancer types in humans

Vishwambari Tamary, MBBS, CCRP,
Medical Advisor and Consultant at the
International Clinical Research Academy
The “CRA-School” of Montreal

References

1. CircRNAs in cancer metabolism: a review: Tao Yu, Yanfen Wang, Yu Fan, Na Fang, Tongshan Wang, Tongpeng Xu& Yongqian Shu Journal of Hematology & Oncology ( https://link.springer.com/article/10.1186/s13045-019-0776-8#Fig2 )

2. Tip of the Iceberg: Roles of CircRNAs in Cancer Glycolysis Tan Li,¹Hong-chun Xian,² Li Dai,¹ Ya-lingTang,² and Xin-huaLiang¹ (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039208/)

Quebec is the only entirely francophone province of Canada

The official language in Quebec is only French. It is the only province, where French is the language of the majority of the population (79%), and the only province in Canada, in which it is the sole official language. Despite that fact, a lot of people speak both languages, especially the younger generations. This makes it a great place to live and work for newcomers from francophone countries.

Two types of French are spoken in Canada, the French, spoken in Quebec and French spoken by Acadians in New Brunswick, which has a different accent. Some other provinces like New Brunswick, Ontario and Manitoba, also have areas with some francophone population. In New Brunswick they are about 28% of the population. Alberta, Saskatchewan, British Columbia, Nunavut, and Newfoundland have very small populations of French speakers, less than 1% of their population.

French has been recognized as an official language together with English in the Official Languages Act of 1969 and both languages are recognized as having equal status in the government of Canada. To work in public institutions you need to be fully bilingual.

Why jobs in clinical research require bilingual staff.

Face-to-face interaction on-site, particularly outside of Montreal, may be primarily in French. In many regions, some older study participants, site staff, vendors, and other stakeholders may be unilingual Francophones. Therefore, in Quebec the interviews for clinical research jobs are always in both languages.

French is always required in Quebec even if all the work in phase III of the clinical trials is done in English. Clinical trials are always international and are conducted in 36-38 countries or more to study the effects on the new product on different ethnic groups. The protocol, the Sponsor SOPs, the study documents and correspondence are in English, as this is the only common language of communication. However, the study subjects do not always speak English. Hence the need of bilingual staff.

This said, not all the jobs require to communicate with external partners, like for ex., Data Management roles, but your French will still be verified. Due to the high shortage of experienced staff, you may soon be offered a promotion to some role, requiring more communications in French. Not speaking it will limit your career growth.

For most of the roles, perfection in French is generally not required, unless it involves writing publications and articles. The goal is to be functional, to understand what you need to do, and do it correctly, and to make yourself understood during interactions with the others and at telephone communications. So relax and take it easy.

What is the solution for this challenge

The requirement of speaking French is blocking the way for foreign-trained candidates, who for family reasons or other considerations decide to settle in Quebec. For those, who come to study in an Anglophone university like McGill or Concordia, and who are considering to stay in Quebec, the only solution to this challenge is to start studying French as early as possible. When you finish your studies it will be too late.

It may take a few years to become sufficiently functional in the language. The time during the immigration procedures is a good opportunity to prepare in advance, and also to acquire more points for the Express Entry program. Demonstrating that you are highly motivated and do what it takes, positions you as a reliable future contributor.

There are many online courses for beginners, which provide the needed flexibility. We also offer such a service. After arrival, there are free French courses organized by the government, where you can continue to improve your French. Having already some initial knowledge will help a lot, and you will show a good proof that you are actively working to increase your qualification. Employers like proactive and passionate people.

Conclusion:

With the right spirit of picking up French along with fundamental Clinical Research skills, Quebec is a great place to work and grow in this field. Bilingual staff is in big demand all the time because other provinces also have francophone population. All our bilingual students got jobs and we are short of bilingual candidates to refer.

Start working on that issue in advance to be ready for applying immediately after arrival and avoid delaying your access to these rewarding jobs.

P.S. If you are interested to learn how you can learn or improve your language skills without losing time and money, send a request by email to info@cra-school.com and you will get a detailed publication with many practical suggestions how to do it.

The International Clinical Research Academy (ICRA), formerly known as CRA-SCHOOL MONTREAL, has been created in March 2009 with the commitment of helping highly educated people worldwide with university and nursing diplomas  enter the rewarding and well-paid field of clinical research careers on unapproved new drugs, vaccines and medical devices for the pharmaceutical and medical devices industry. 

In this spirit, and to help alleviate the financial burden for candidates in conditions of  rapidly growing inflation, the Global Accessibility Program (GAP) has been reactivated.

What is GAP

The Global Accessibility Program (GAP) offers additional regional discounts based on the disparity of the economic realities of some areas, including many countries in Africa, South America and Asia.

The objective of the GAP program is to increase the accessibility to these well-paid careers with chronic shortage of qualified staff for every candidate in the world.

GAP Eligibility by region:

If you are in Africa, South America, or Asia, please get in contact with us today by email at info@cra-school.com to see if your country is eligible for an additional reduction in the enrollment fees based on your country of residency.

* This  additional tuition fees reduction is not available for residents of North America and Europe.

1-hour free consultation on the clinical research careers & discussion of a suitable Action Plan

The concept of this program is quite unique. It combines a very comprehensive regulatory training with 3 remote part-time monitoring internships to provide the required practical experience and 1-on-1 Placement Assistance Till Hired (PATH)

For a detailed 1-hour consultation and to get answers to all your questions, connect to our 7/7 LIVE support, provided 7 days per week till midnight EST (UCT-5).

Just say “Hi” to our Skype account CRA SCHOOL MONTREAL (the account without a dash between CRA and School) or book a consultation at info@cra-school.com.

It is a free service.

Become Affiliate of the International Clinical Research Academy CRA-School – Montreal

Kindly share the information with colleagues and friends who may profit from this opportunity. You will get 10% Referral bonus whenever anyone enrolls in the program

Contact us for more details

On occasion of the Cinco de Mayo, the Battle of Puebla, CRA-School Montreal (ICRA) offers a special additional 10% discount to Mexicans worldwide, who enroll for the Spring Session of the PG Clinical Research Professionals Certification and On-boarding program CRP_3.0 with 3 remote internships and unlimited Placement Assistance Till Hired.*

The reduced price of CAN$ 971.00 (or its equivalent in US$) is valid till May 15th midnight.
Enter the promo code ICRAMEXICO in the coupon field at checkout.

This is an individual, self-paced online PG program, not in a group, and it takes 3 to 6 months to finish depending on student’s availability. The support is adapted to the objectives and the qualifications of every student. It starts immediately after enrolling, and has unlimited duration (till hired).

The 7/7 LIVE Support is provided by Skype chat directly from tutors and Level II instructors 7 days/week till midnight EST (UCT-5) to fit the availability of the students in different time zones. This allows to combine study with work or other studies.

Share with friends who may profit and get $100 Referral bonus when any of them enrolls.

______________________________________________________________________

* Our concept how to help IMGs to get a 1-st job in the clinical trials industry is rather atypical. Besides the very detailed regulatory training on the US, Canadian and international clinical trials regulations (over 1000 pages because the goal is to answer successfully any question at an interview and get the job), it includes 3 part-time remote internships to provide “hands-on” experience in Canadian/US regulatory environment, as required by law (and make the students eligible for the interviews), networking coaching to become known and get job leads about the “hidden” jobs (80-90% of all vacancies are never published, but filled-in by internal promotions and references), and CV adaptation support for every job, with unlimited interview practice and preparation for every role (till hired).

This program is internationally accredited and recognized by Transcelerate Research – USA.
It provides a PG professional diploma of a Certified Clinical Research Professional (CCRP) and covers not only the role the field CRA (the monitor and auditor), but also the roles of the CRC, CTA, IH-CRA, RA, DM, and PM.

Several entry-level jobs are also covered, like Data Entry Assistant, Documentation Assistant, Study Feasibility Assistant, Patients Recruitment Assistant, IRB and Regulatory Applications Assistant, Study Start-up Assistant etc.

We provide support also for top-level jobs that require high medical qualification, like Clinical Scientist, Medical Writer, Medical Monitor, Medical Assistant, Medical Affairs, Project Manager, Study Manager, Study Director, Drug Safety or Pharmacovigilance Associate and MSL (Medical Scientific Liaison)

The clinical research industry is a great alternative for foreign-trained RNs, MDs, BDS, veterinarians, pharmacists. biochemists, biologists and BSc/MSc/PhD degree holders
(No need for recognized diplomas, exams, nor license to practice)

* Regulatory Affairs jobs, including Clinical Data QC/QA, Drug Safety & Pharmacovigilance
* High wages, fast access (4-6 months detailed self-paced training with 3 remote internships in parallel to the regulatory training + unlimited 7/7 LIVE support in interview preparation till hired

The International Clinical Research Academy (ICRA), formerly CRA-School of Montreal, offers this program since 2009. It was the first program to include internships, a key requirement for getting hired. Internships are still extremely rare due to confidentiality & liability reasons.

You can find our former graduates and current students on LinkedIn, feel free to contact them. Career change is an important step, and to make a well-informed decision requires to get the maximum of information from several different sources.  Do not jump in the water if you don’t know what  is under the surface.

Schedule a free 1-hour consultation here

End of the special 45% reduction for the

PG Clinical Research program CRP_3.0

During the first lock-down, the Executive Board of the International Clinical Research Academy “CRA-School” – Montreal decided to help people blocked at home to use the time for acquiring new qualifications in the rewarding field of the clinical research industry, which is in chronic shortage of qualified research staff, and offers higher than the average salaries, with frequent promotions.

* Therefore, two years ago, the board has decided for the duration of the lock-down to work temporarily without generation profits and granted a special 50% temporary discount for the unique concept of the individual online PG Clinical Research On-boarding program CRP_3.0 with 3 remote internships and unlimited Placement Assistance Till Hired (PATH). It is an individual, self-paced online program, with immediate 7/7 LIVE SUPPORT, provided till midnight EST (UCT-5).

Last week of the old 2021 fees with 45% discount for the PG Clinical Research On-boarding program with 3 internships and unlimited Placement Assistance Till Hired.

* Unfortunately, nobody expected that the lock-downs will become systematic, and the next year the discount had to be reduced to 45% to continue covering the operation costs and provide the highest quality services to the students. However, the high yearly inflation in 2021 made it difficult to cover the raising costs and maintain the 2021 tuition fees without cutting in the services.

In this situation, another reduction of this special discount becomes necessary. This is the LAST WEEK of the old 2021 fees with a 45% discount. It will expire on March 31 at midnight EST, and the new, corrected fees for 2022 will enter in force in April.

Payment in 2 monthly installments can also be selected during the inscription. For immediate assistance, just say “Hi” to our Skype account CRA SCHOOL MONTREAL. The 7/7 LIVE support is provided by chat till midnight EST (UCT-5). The service is free.

Please share with friends and colleagues who may be interested to profit from this last opportunity. Fees can be corrected without prior notice if the economic situation changes.

The well-paid careers in the clinical trials industry are an interesting alternative for foreign-trained physicians, dentists, veterinarians, nurses, pharmacists, biologists, chemists, and any other life-science professionals. Neither recognized diplomas, nor license to practice are required. In Regulatory affairs, only the licensed staff perform medical acts. All the other staff work on the Quality Control (QC) of the generated data, its documentation according to the Good Documentation Practice (GDP), and on assuring the compliance of all activities with the approved protocol and applicable regulations.

The Administrative Board of ICRA, The CRA-School

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Global Networking Series – live webinar WOMEN IN CLINICAL RESEARCH – DIVERSITY IN ACTION March 8, 2022.

Special event on occasion of March 8,

    the International Women’s Day

Tuesday, March 8, from 12:00 till 1:00 PM EST, Montreal time (UCT-5). 

Join us during your lunch break. Open panel discussion by Zoom. 

Meet 3 inspiring women with different origin from the clinical trials field

• A Senior Project manager, who set studies in 15 African countries,
• A Medical Writer, who trains Medical Writers, and
• A Clinical Research Coordinator, graduate of CRA School.

Learn about their careers, challenges they faced & their achievements.

Hear tips & advice from these seasoned panelists, ask any questions.

Register here to get the password how to join the Zoom Meeting.

Recording provided if you are not available at that hour.

FREE EVENT 

Best time to access a rewarding clinical research career in the clinical trials industry

• The offer

Last chance to offer to your loved one a new clinical research career in the rewarding clinical trials industry with a 45% discount for the Valentine Day. Tuition fees will be corrected with the inflation before the end of February after this offer expiry. 

Now the package offer provides for free also a Good Documentation Practices training (GDP) and the Medical devices regulations. Internationally harmonized regulations, qualification recognized worldwide.

• Added value

The PG diploma includes the International GCP E6(R2) guidelines, the US FDA & NIH regulations, the Health Canada F&DA, division 5, plus 3 remote internships to provide the required “hands-on” experience and 7/7 Live Support till midnight.

Placement Assistance Till Hired (PATH), networking support and professional branding, unlimited CV adaptation coaching for every role, and interview preparation till getting the first job and 3 months afterwards are integral part of the program.

• Clinical research careers 

Clinical research careers are an excellent alternative for international health & life sciences graduates, facing a career change: nurses, physicians, dentists, veterinarians, physiotherapists, pharmacists, biologists, biochemists, medical & lab technologists, MSc & PhD graduates, etc.

Neither recognized diplomas, nor license to practice are needed; No night and weekend shifts, no handling of biological fluids. The clinical research careers are in Regulatory Affairs, and most jobs became remote and home-based. 

• The right time to join

Join the winners in the most important and always growing industry of the world, with a chronic 30% shortage of experienced staff and automatic promotions every year because of that huge demand.

Presently, a lot of companies try to develop vaccines that work, but a vaccine trial needs 40,000 subjects vs 4,000 for drugs. This requires a lot of new staff. There have never been that many well-paid new jobs in the rewarding clinical trials industry.

It is the right time to get in. The companies hire like crazy. Don’t miss the opportunity. Once you get in, you will be in forever.

• How to join

Short-term offer for the Valentine day only, expires on February 24, 2022.

Validity: 10 days (till our Professional Networking Event with CREMCV on February 24)

To register, go to the menu ENROLL, select the combined course CRP 3.0 and Payment in 1 installment or in 2 installments, click the button ADD TO CART at the bottom of the screen, then enter your credit card number.

• Consultations

Book a free consultation or contact us by Skype at our account CRA SCHOOL MONTREAL

SÉRIE DE RENCONTRES MENSUELLES DE RÉSEAUTAGE GLOBAL DE CRA-SCHOOL MONTRÉAL

Edition Février 2022

CRA-School a invité CREMCV, un organisme d’aide aux nouveaux arrivants, spécialisé à accompagner les nouveaux-arrivants et les professionnels de la santé formés hors du Canada, dans leurs demarches de trouver une application adéquate de leur compétences.

La gestion de la pandémie et les essais cliniques des nouveaux vaccins* génèrent beaucoup de nouveaux emplois inconnus, et souvent, non affichés, mais comment faire pour en avoir vent si une grande partie ne sont pas affichés? La réponse est: Réseautez 

Venez nous joindre par Zoom le 24 février 2022 de 17h00 pour entendre les conseils des experts de CREMCV et apprendre comment dénicher les postes dans le domaine de la santé à l’aide d’un réseautage professionnel actif.

Événement gratuit. SVP partagez l’information avec vos amis et collègues, qui pourraient en profiter.

Enregistrez vous sur https://bit.ly/34I38Mb pour obtenir le lien et le mot de passe pour la rencontre

____________________________
* L’essais clinique d’un vaccin exige 40,000 participants, contre 4,000 seulement pour un médicament.
  Ceci demande 10 fois plus de personnel que d’habitude. L’embauche n’a jamais été aussi active.
  Plusieurs compagnies sont entrées dans la course pour développer un vaccin qui marche mieux.
  C’est le meilleur moment d’entrer dans ce domaine, mais comment, si on n’y connait personne?

Des consultations gratuites pour cadres de la santé, formés hors du Canada (infirmières, médecins,
dentistes, vétérinaires, pharmaciens, biochimistes, biologistes, MSc et PhD) sur les carrières en
Affaires Réglementaires dans l’industrie des essais cliniques, qui ne demandent ni diplôme reconnu,
ni licence à pratiquer, sont procurées aussi par Skype 7 jours par semaine jusqu’à minuit. Juste envoyez
une invitation à notre Support à CRA School Montreal, ou réservez sur le site l’heure qui vous convient.