dream designs

Combination Of Conventional And New Drugs Enhances Tumor Cell Death

ArticlePress release
Current Medical News
Contributed byMaulik P. Purohit MD MPHAug 29, 2017

Cancer is one of the major causes of death worldwide affecting 8.2 million of people per year, and in the US, the number of new cases will achieve 1.6 million in 2017. The global impact of this disease costs a trillion of dollars, which makes critical the development of new drugs and treatment against it.

In a recent study published in the scientific journal Translational Oncology, researchers from the Federal University of Rio de Janeiro (UFRJ), State University of West Zone, (UEZO) and D'Or Institute for Research and Education (IDOR) tested the therapeutic effect of a combination of conventional -- common anti-cancer agents -- and new drugs -- under clinical trials. "The results were very exciting because the successful outcome depended on the chemotherapy regimens. On the other hand, "wrong" combination of drugs could elicit harmful effects," states Helena Borges, professor at Institute of Biomedical Sciences of UFRJ, and study leader.

The disease

Cancer is characterized by abnormal cell growth that invades other parts of the body. It is known that this abnormal pattern of cell growth depends on several signaling mechanisms inside the cells involving the protein pRB. pRB plays multiple roles, including controlling cell division, which prevents abnormal growth. In cancer cells, both cell division and apoptosis (programmed cell death) are impaired because tumor suppressor agents, such as pRB, are not fully available. As a result, cell number increases drastically since cell death and division do not occur appropriately.

Many anti-cancer drugs widely used were developed more than 50 year ago, when the cancer-related cellular mechanisms were poorly understood. Among them, cisplatin and 5-FU act inducing DNA damage or preventing DNA production, leading to a reduction of cancel cells. Recent findings about the central role of pRB on cancer revealed it is a potential target for treatments with fewer side effects. Indeed, new drugs were developed to act on the pRB pathway, fostering its functioning and allowing the appropriate control of cell growth. Some of these drugs are under clinical trials and may be incorporate as alternative anti-cancer treatment soon.

The study

Researchers from Rio de Janeiro investigated whether cisplatin and 5-FU would be able to interfere with pRB. Also, they evaluated the impact of the drugs on tumor cell death induction and on the standard treatment against cancer.

First, they described that the signaling pathway in which the pRB plays a key role is impaired in esophageal cancer, the sixth most common cause of cancer-related death worldwide. Human esophageal biopsies coming from non-tumoral tissue, esophageal pre-cancer and advanced stages of disease were assessed for pRB expression. As a result, a positive correlation between pRB expression and cancer progression was observed: the more advanced the stage of the esophageal tumor, the greater pRB inactivation was found.

"This result reinforces the notion that impaired pRB signaling contributes for the esophageal cancer progression," points Prof. Borges.

Then, researchers focused on a family of proteins responsible for pRB inactivation, named CDKs. Blocking CDKs' activity is the mechanism of action of new anti-cancer drugs under clinical trials.

The group aimed to clarify whether blocking CDKs combined with conventional drugs, such as cisplatin and 5-FU, would increase cell death, making the treatment more effective.

The analyses revealed that blocking CDKs, associated with cisplatin, increased mortality of tumor cells. On the other hand, opposite effects were observed when treating cells with 5-FU: esophageal cancer cells became resistant to the drugs, showing decreased death rates.

Stevens Rehen, researcher from IDOR and professor at the Institute of Biomedical Sciences/UFRJ, co-author of the study, highlights the importance of gathering knowledge of cell biology in order to strategically identify and test anti-cancer drugs.

"The results bring attention to studies that investigate the combination of CDKs' inhibitors and conventional anti-cancer drugs. CDKs' inhibitors seem to enhance the treatment, but depending on the situation, combining them with 5-FU can be disastrous" says Prof. Borges. New studies have been conducted to investigate the effects of specific CDKs' inhibitors on new combinations of several types of cancer.


Materials provided by D'Or Institute for Research and EducationNote: Content may be edited for style and length.

Disclaimer: DoveMed is not responsible for the accuracy of the adapted version of news releases posted to DoveMed by contributing universities and institutions.

References:

Rossana C. Soletti, Deborah Biasoli, Nathassya A.L.V. Rodrigues, João M.A. Delou, Renata Maciel, Vera L.A. Chagas, Rodrigo A.P. Martins, Stevens K. Rehen, Helena L. Borges. (2017). Inhibition of pRB Pathway Differentially Modulates Apoptosis in Esophageal Cancer CellsTranslational Oncology. DOI: 10.1016/j.tranon.2017.06.008

Was this article helpful

On the Article

Maulik P. Purohit MD MPH picture
Approved by

Maulik P. Purohit MD MPH

Assistant Medical Director, Medical Editorial Board, DoveMed Team

0 Comments

Please log in to post a comment.

Related Articles

Test Your Knowledge

Asked by users

Related Centers

Loading

Related Specialties

Loading card

Related Physicians

Related Procedures

Related Resources

Join DoveHubs

and connect with fellow professionals

Related Directories

Who we are

At DoveMed, our utmost priority is your well-being. We are an online medical resource dedicated to providing you with accurate and up-to-date information on a wide range of medical topics. But we're more than just an information hub - we genuinely care about your health journey. That's why we offer a variety of products tailored for both healthcare consumers and professionals, because we believe in empowering everyone involved in the care process.
Our mission is to create a user-friendly healthcare technology portal that helps you make better decisions about your overall health and well-being. We understand that navigating the complexities of healthcare can be overwhelming, so we strive to be a reliable and compassionate companion on your path to wellness.
As an impartial and trusted online resource, we connect healthcare seekers, physicians, and hospitals in a marketplace that promotes a higher quality, easy-to-use healthcare experience. You can trust that our content is unbiased and impartial, as it is trusted by physicians, researchers, and university professors around the globe. Importantly, we are not influenced or owned by any pharmaceutical, medical, or media companies. At DoveMed, we are a group of passionate individuals who deeply care about improving health and wellness for people everywhere. Your well-being is at the heart of everything we do.

© 2023 DoveMed. All rights reserved. It is not the intention of DoveMed to provide specific medical advice. DoveMed urges its users to consult a qualified healthcare professional for diagnosis and answers to their personal medical questions. Always call 911 (or your local emergency number) if you have a medical emergency!