Vascular malformations: a new hope due to molecular targeted anti-tumor strategies

Emmanuel Seront, Valérie Dekeuleneer, Julien Coulie, Ann Van Damme, Laurence Boon, Miikka Vikkula Published in the journal : May 2022 Category : Oncologie

Vascular malformations are rare diseases that result from disturbances in the angiogenesis process. These malformations are subdivided into capillary, lymphatic, venous, arteriovenous, and mixed malformations, according to the type of affected vessels. Until a few years ago, therapeutic options were limited to sclerotherapy or surgery, but these latter treatments were only rarely curative in nature or often not feasible. The majority of vascular malformations are caused by inherited or somatic mutations in various genes. Of note is that these mutations are similar to oncogenic mutations detected in cancer conditions, causing hyperactivity of essential signaling pathways, including the MAPK and PI3K/AKT/mTOR cascades. In this article, we have highlighted the role of targeted molecular inhibitors as possible therapies for vascular anomalies via repurposing of anticancer drugs.

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Improved patients’ prognosis by using innovative treatments at earlier stages

Jean-Francois Baurain, Jean-Pascal Machiels, François Duhoux Published in the journal : February 2019 Category : Oncologie

There has been no revolution in the oncology field in 2018. We have, however, been able to further confirm the major benefits of immunotherapy for patients with metastatic cancers. Anti-PD1 antibodies have now become the standard of treatment for head and neck cancers, bladder cancers, melanoma, lung carcinomas, kidney cancers, and cutaneous spinocellular carcinomas. Based on mature survival data, we’ll likely be able to cure numerous metastatic cancer patients. Amongst targeted therapies, PARP inhibitors will possibly be more effective in terms of increased progression-free survival. These inhibitors block one of the two DNA repair mechanisms and are active in ovarian cancer patients responding to platinum salt-based chemotherapy. At present, we are witnessing another prognosis improvement in our patients, as a consequence of using these agents at earlier stages and preventing relapse after curative surgery in patients at high-risk of relapse. At the King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Brussels, these treatments are now available, as are other new treatments still being investigated, which may become the standard of care in the future.

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Immunotherapy and targeted therapies are standard of care in oncology

Jean-François Baurain, François Duhoux, Astrid De Cuyper, Frank Cornélis, Jean-Pascal Machiels, Thierry Pieters Published in the journal : February 2018 Category : Oncologie

2017 was again a great year for oncologists, as the efficacy of new promising drugs and treatment modalities could be confirmed, thus improving the prognosis of our patients. Since we cannot describe all highlights here, we decided to focus on some major advances. Immunotherapy with anti-PD-1/PD-L1 antibodies has become a standard of care in many metastatic patients, with a long-term survival benefit reported for some of them (yet it is too early to talk about cure). However, the administration of these antibodies is associated with a very specific auto-immune toxicity that may have serious or even fatal consequences if not recognized and treated early. Moreover, the range of available targeted therapies is continuously growing, with the advent of new therapeutic classes, such as the CDK 4/6 and PARP inhibitors. Thanks to our better understanding of the mechanisms underlying resistance to targeted therapies, news drugs have been developed (e.g. osimertinib) and have proved able to overcome the resistance observed with the first-generation tyrosine kinase inhibitors in lung cancer. There is also a trend toward decreasing the aggressiveness of chemotherapeutic regimens. All these treatments are available at the King Albert II Cancer Institute, along with new treatments that are currently being investigated and might become the standard of care of tomorrow.

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Krukenberg tumors, osteoblastic metastases, and elevated parathormone levels : clinical case report and literature review

Léopold Pirson (a), Yves Humblet (b), Ingrid Ferreira de Castro Moutinho (c), Christine Galant (c), Dominique Maiter (d) Published in the journal : March 2017 Category : Oncologie

Numerous cases of Krukenberg tumors have been described in the literature, with several reviews on this topic published over these last three decades. The precise origin of these metastatic tumors is often unknown, in spite of the availability of biological and immunohistochemical markers. This case-report sought to present the diagnostic and therapeutic challenges raised by Krukenberg tumours in the course of a poorly-differentiated adenocarcinoma of atypical presentation, along with a review of the literature on this topic. We report the case of a 29-year-old patient referred to the endocrinology department for increased bone turn-over and elevated parathormone levels, in the context of chronic lower back pain. Further examinations revealed bilateral Krukenberg tumors, multifocal osteoblastic bone metastases, as well as probable peritoneal dissemination. While the primary origin of the metastases is still unknown, they are likely of gastro-intestinal origin, following careful exclusion of breast carcinoma. Whereas there are no guidelines on the management of Krukenberg tumors, actual therapy primarily consists of bi- or tri-chemotherapy with bilateral adnexectomy, leading to extended survival from a few months to several years. Yet prognosis remains poor with a median survival time of only 16 months, unless both primary tumor and metastases can be fully resected, with then considerably extended survival.

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Hope for cancer patients due to immunotherapy and the advent of new targeted therapies

Jean-François Baurain, Jean-Pascal Machiels, François Duhoux Published in the journal : February 2017 Category : Oncologie

Major advances in medical oncology were observed in 2016. This article highlights some of these advances. Firstly, a new therapeutic class, the CDK4/6 inhibitors (palbociclib, ribociclib), was discovered, arousing major interest. When combined with hormonotherapy, these inhibitors were shown to increase overall survival of ER-positive metastatic breast cancer patients by several months. Secondly, PARP inhibitors (niraparib) that block one of the two DNA repair mechanisms were shown active in all relapsing ovarian cancer patients with a response to platinum-based chemotherapy. Finally, immunotherapy is now generally regarded as an essential therapeutic modality in the treatment of cancer, with shapes of some survival curves suggesting that some patients could be definitely cured. Ipilimumab, an anti-CTL-4 antibody, was shown able to increase the global survival of resected Stage III melanoma patients at high risk of relapse. The combination of anti-PD1 and CTLA-4 antibodies proved superior to the respective monotherapies in the treatment of metastatic melanoma. Anti-PD1 antibodies currently represent the standard of care in the treatment of metastatic head and neck cancers, kidney cancers, and lung cancers. The administration of these antibodies was associated with a very specific, autoimmune toxicity, which was at times severe or even fatal if not recognized and treated early. All these treatments are presently accessible at the King Albert II Cancer Institute.

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J.-Fr. Baurain, F. Cornélis, F. Duhoux, Y. Humblet, F. Mazzeo, M. van den Eynde, J.-P. Machiels Published in the journal : February 2016 Category : Oncologie

Cancer management has become multidisciplinary, and major advances have been achieved in medical oncology field over the last years. The year 2015 was marked by a change in the treatment strategies for metastatic prostate cancer, with docetaxel-based chemotherapy being now initiated concurrently with castration. This allows for a 10-month increase in median overall survival in these patients, thereby representing a major breakthrough. Last year, a new kind of targeted agent, olaparib, was also granted reimbursement for the treatment of platinumsensitive ovarian cancer. This inhibitor of PARP, a major protein involved in DNA repair, was shown to significantly increase recurrence-free survival in BRCA-mutated ovarian cancer patients. BRCA is a key protein involved in the second DNA repair mechanism. Lastly, the most impressive oncological advance achieved last year pertained to the introduction in daily practice of the anti-PD1 or PDL1 antibodies. Several studies, conducted mostly in melanoma patients, have shown this immunotherapy to be highly effective, with possible cancer cure for some patients. Administering these antibodies is, however, associated with very specific toxicity features, namely autoimmune toxicity that may be severe or even fatal if not recognized and treated early. All these treatments are available at the King Albert II Cancer Institute.

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