cariplo foundation Archives

April 15, 2022April 15, 2022

Our review on cardiotoxicity of anticancer therapies is online!

Unfortunately, anticancer drugs can induce side effects on heart tissue. This phenomenon, known as cardiotoxicity, in severe cases, can reduce the quality and life expectancy of cancer patients, regardless of the oncological prognosis.

The good news is that the complex molecular mechanisms responsible for these effects in different classes of anticancer drugs are beginning to emerge, and as a result, potential therapeutic approaches to protect the heart from these effects are beginning to be proposed.

#cardiotossicità #farmaciantitumorali #ricercascientifica #medicina #salute #unibo #irccsmultimedica #conFondazioneCariplo

Abstract: Chemotherapy and targeted therapies have significantly improved the prognosis of oncology patients. However, these antineoplastic treatments may also induce adverse cardiovascular effects, which may lead to acute or delayed onset of cardiac dysfunction. These common cardiovascular complications, commonly referred to as cardiotoxicity, not only may require the modification, suspension, or withdrawal of life-saving antineoplastic therapies, with the risk of reducing their efficacy, but can also strongly impact the quality of life and overall survival, regardless of the oncological prognosis. The onset of cardiotoxicity may depend on the class, dose, route, and duration of administration of anticancer drugs, as well as on individual risk factors. Importantly, the cardiotoxic side effects may be reversible, if cardiac function is restored upon discontinuation of the therapy, or irreversible, characterized by injury and loss of cardiac muscle cells. Subclinical myocardial dysfunction induced by anticancer therapies may also subsequently evolve in symptomatic congestive heart failure. Hence, there is an urgent need for cardioprotective therapies to reduce the clinical and subclinical cardiotoxicity onset and progression and to limit the acute or chronic manifestation of cardiac damages. In this review, we summarize the knowledge regarding the cellular and molecular mechanisms contributing to the onset of cardiotoxicity associated with common classes of chemotherapy and targeted therapy drugs. Furthermore, we describe and discuss current and potential strategies to cope with the cardiotoxic side effects as well as cardioprotective preventive approaches that may be useful to flank anticancer therapies.

Go to the original article: Morelli MB, Miano C, Bongiovanni C, Sacchi F, Da Pra S, Lauriola M and D’Uva G. Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms and Strategies for Cardioprotection. Frontiers in Cardiovascular Medicine, 2022

March 26, 2022April 15, 2022

Our study unveils a potential role for Neuregulin-ERBB3-ERBB2 signalling axis in basal-like / triple-negative breast cancer

Breast cancers called “triple negative” and “basal-like” are particularly aggressive subtypes of breast cancer, with fewer treatment options.
Our results, just published in the journal “Cancers“, suggest that in these tumor subtypes the activation of a cellular signaling pathway composed by the growth factor Neuregulin and the ERBB3 and ERBB2 receptors may confer to cancer cells an increased ability to grow in absence of adhesion, consequently supporting the dissemination of tumor cells and the growth of metastases.
Therefore, our study suggests to evaluate, through further experiments, the administration of Neuregulin-ERBB3-ERBB2 axis inhibitors, in particular anti-ERBB2 drugs already used in the clinic for the treatment of other tumor subtypes, as a potential therapeutic strategy for basal-like / triple-negative breast cancer patients .

Congratulations to Dr. Carmen Miano, postdoc researcher of our research group and first author of the article, as well as to the other members of our group and external collaborators who have helped and supported us in the execution of the experiments and in the advancement of the project.

We deeply thank #AIRC and #FondazioneCariplo for their financial support of the project.

Go to the full article: Miano C, Morselli A, Pontis F, Bongiovanni C, Sacchi F, Da Pra S, Romaniello D, Tassinari R, Sgarzi M, Pantano E, Ventura C, Lauriola M, D’Uva G. NRG1/ERBB3/ERBB2 Axis Triggers Anchorage-Independent Growth of Basal-like/Triple-Negative Breast Cancer Cells. Cancers, 2022

April 13, 2018April 13, 2018

Fellowship opportunity in our lab

We are recruiting a research fellow at MultiMedica ONLUS Foundation (Milan). The contract is for 1 year, starting from June 2018, and potentially renewable for a total of three years.
The project is funded by Cariplo Foundation and the research will be conducted in our laboratory, which forms a bridge between the fields of cancer, cardiotoxicity of anticancer therapies and cardiac regeneration.

The selected research fellow will develop a project on the cardiotoxicity of anti-cancer therapies. Cardio-toxicity is a common side effect of chemotherapy and targeted anti-cancer therapies, strongly impacting on the quality of life and the overall survival, regardless of the oncological prognosis. The goal is to develop strategies for reducing the cardiotoxic side effects of current anti-cancer therapies, while simultaneously improving their efficacy. By employing both breast cancer cells and primary mouse cardiomyocytes cultures in vitro, the research activities will be focused on the role of specific growth factors and receptors on cell differentiation status, and the impact on tumour growth and cardiotoxic side effects. In vivo analysis on mouse models will also be conducted.

Applicants requirements: Applicants must have a molecular-, cell- and biochemistry backgrounds, such as a Master Degree in Biotechnology, Biology or related field. Candidates must have at least one year of experience in a research laboratory. Familiarity with standard molecular biology techniques (Real Time PCR, Western Blot, Immunofluorescence analysis…), as well as the expertise in cardiac and/or tumour biology, are required. Passion for science as well as a positive attitude towards solving problems is required in order to pursue technically challenging and intellectually stimulating projects in the lab.

Other criteria: PhD Degree is not required, but is positively evaluated. Expertise in procedures for the induction of cardiac damage (by cardiotoxic drugs or myocardial infarction) as well as in the analysis of microarray o RNA-seq datasets is a plus factor for the selection process.

How to apply: Applicants should send their CV by email with subject line “Research fellowships at Fondazione MultiMedica ONLUS” to Dr. Gabriele D’Uva (gabriele.duva@multimedica.it). One or more letters of recommendation are welcome, although not strictly required. Interviews will be conducted for selected candidates until the position is filled.

Previous publications relevant to the project:
• D’Uva G et al., ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nature Cell Biology, 2015
• D’Uva G and Tzahor E, The key roles of ERBB2 in cardiac regeneration. Cell Cycle. 2015
• Yutzey KE. Regenerative biology: Neuregulin 1 makes heart muscle. Nature, 2015 (News & Views on our article)
• D’Uva G and Lauriola M, Towards the emerging cross-talk: ERBB family and steroid hormones. Seminars in Cell and Developmental Biology, 2016