Editor’s foreword: evolving the rare cancer field

KEYWORDS:

• Rare cancers
• BRAF mutant melanoma
• drug regulation
• drug repurposing
• cholangiocarcinoma
• giant cell tumor of bone; patient voice; PEComas

According to a report by RARECAREnet, rare cancers accounted for 24% of all cancers diagnosed between 2000 and 2007, and the challenges in diagnosing and treating rare cancer patients are increasingly being recognized [1]. In addition, the difficulties of developing new medicines for small populations is now being seen for the traditionally classified common tumors, as these tumors are reclassified into multiple rare subsets based on the molecular features of the disease. Thus, the total number of eligible subjects may be very limited for rare cancer research, impacting the choice of the study design and the statistical methodology, and requiring the coordination of numerous trial sites across the globe. Whatever the approach employed, the requirement for statistical efficiency should be balanced against the need for drawing clinically relevant and scientifically robust conclusions [2]. Indeed, strategies that are based around pragmatic approaches and novel trial designs may help maximize the completeness of the eventual evidence base that supports both clinical and regulatory decision-making [3]. Collaborative approaches, such as the European Reference Networks (e.g. European network for Rare adult solid Cancer, ERN EURACAN), are also helping to bring together expertise from across Member States. These networks support the exchange of knowledge, fostering strong links that are conducive for promoting efficient clinical research and evidence generation [4].

Over 300 rare cancers have been identified and this special issue on rare cancers touches on aspects across the whole spectrum of the drug development pathway, including European regulatory views on pediatric oncology, examples of in-depth therapeutic and disease analysis in four different cancers, reflections from the dynamic field of drug repurposing and perspectives from a patient advocate on the changing rare cancers landscape. This special issue highlights the many ongoing advances and future opportunities in what was once a neglected space in oncology and cancer research.

The knowledge of the biology of rare cancers continues to grow at pace and the discovery of molecular alterations has created the expectation for the arrival of new (and established) targeted therapies to treat patients. This is a common theme running across the four papers on individual tumors. Squires et al. present some of the exciting treatment advances for cholangiocarcinoma [5], where improvements in the molecular understanding of the condition have led to the identification of multiple actionable mutations, moving away from traditional chemotherapy to targeted medicines. Ben-Ami et al. comprehensively discuss the emerging new therapeutics in perivascular epithelioid cell tumors (PEComa) [6]. Highlighting the diagnostic challenges for this particular tumor and the growing understanding of the role of mTOR pathway activation, offering the potential for patients to be treated with mTOR inhibitors. Views on the management of giant cell tumour of bone are presented in a review by Zdzienicki et al. [7]. Giant cell tumor of the bone is a locally aggressive tumor where deregulation of the RANK/RANK-ligand pathway has been reported. Alongside conventional surgery, anti-tumor activity of a monoclonal antibody that targets and binds RANKL has been observed and this has transformed the medical options for these patients. In a review on BRAF mutant melanoma, Eroglu and Ozgun provide updates on the currently available BRAF and MEK inhibitors, noting that although these targeted therapies are effective for most patients, acquired resistance may develop and there are outstanding questions on how to best sequence these drugs [8]. Ongoing trials are also exploring other combinations with emerging novel treatments such as immunotherapies.

In a regulatory perspective, Karres et al. discuss the impact of the European Union’s pediatric regulation which came into force in 2007 [9]. They highlight how collaboration and joint interactions between different stakeholders (patient-industry-academic-regulator) can improve timely access to novel medicines for children with cancer, providing some reflections on the potential opportunities that might further accelerate successful pediatric oncology drug development. Repurposing is a dynamic and innovative field of medicines research. Pantziarka and Meheus provide intriguing practical insights into how molecularly guided approaches in precision medicine can be used to repurpose non-oncology drugs in rare cancers. The benefits of repurposing are balanced against the challenges, in particular, the funding gap due to the lack of commercial sponsorship. However, the significant advantages of repurposing are clear, and this field may help address unmet medical need for rare cancer patients [10]. 

In a patient advocacy perspective, Kathy Oliver from the International Brain Tumour Alliance provides inspiring and personal reflections on the changing landscape of rare cancers, articulating how rare cancers are now the focus of an improved level of attention. Oliver reiterates the importance of the innovative and collaborative initiatives that have emerged in recent years, putting rare cancers firmly on the European policy agenda and providing solutions to some of the many challenges [11].

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.