Leading the path in precision oncology for rare cancers


Personalized or precision cancer medicine represents a departure from traditional ‘one size fits all’ strategies to treat cancer and extends the concept of stratifying treatment for a particular tumor based on clinicopathological features to a more intricate, individual level. Extensive cancer sequencing data describing the genetic landscapes of human cancers is now used to identify actionable mutations using targeted therapy, e.g., targeting oncogenes or using a synthetic lethal approach. International efforts providing a pan-cancer comparison of the genomic similarities of tens of thousands of patients now suggest shifting the grouping of cancers towards tissue-agnostic subtypes defined by the genomic aberrations rather than the tissue or cell of origin. This has a profound impact also on the way cancers could be treated as classically cancer treatment strategies have been considered cancer type specific and developed through large clinical trials focusing on one single cancer type.

The problem

Today, it is clear that cancer heterogeneity has been largely underestimated. The hundreds of different forms of cancers originating from different sites of organs and the different cell-of-origin are driven by a complex array of genomic driver and passenger alterations and no two cancers are identical. Thus, it is easy to argue that no two cancers respond similarly to a given therapy, even if having a similar genetic background. The outcomes reported from recent genomics informed clinical trials are in support of this as the overall response rates achieved through genomics matched therapies have not been substantially better than those achieved with standard therapies. How do we then match the patients with the best treatment in the future?

The solution

The ability to functionally confirm a patient’s tumor cells´ sensitivity towards targeted therapeutics following a genetic profiling could provide the needed evidence to use such therapeutics also to treat other cancers, especially rare cancers for which conventional clinical trial designs are not possible due to the low numbers of cases. A diagnostic method to confirm the patient specific efficacy of a drug before each treatment decision may well be the only way to demonstrate efficacy of novel targeted therapies for rare cancers. To allow this, we are pioneering a platform for ex vivo therapy efficacy screening for rare solid cancers. Feasibility of the platform´s utility has been demonstrated in a pre-clinical study of hundreds of patients covering 60 different solid cancer types including some of the rarest cancers in the world.

What we do

Ex vivo drug screening in rare solid cancers

“We are developing tissue agnostic ex vivo evidence based personalized medicine for rare solid cancers.”

The definition of rare cancers is based on the incidence rate of 50 cases per 100.000 people. In Europe, the overall incidence rate of rare cancers is 114 per 100.000 and these account for ~22% of all new cancers diagnosed in Europe. Due to the low incidence rates of individual rare cancer types, the tumorigenesis of many of these malignancies is largely unclear and due to low number of cases there is little literature on e.g. common genetic aberrations that would confer to targeted treatment strategies, and moreover, the low number of cases prevents completion of systematic clinical trials. Treatment regimens used in rare cancer care are thus mainly based on surgery and radio- and/or standard chemotherapy. To allow patient specific assessment and clinical utilisation of targeted therapeutics for rare cancer care, we have developed a methodology to determine the anti-tumoricidal effects of hundreds of treatment options within days from the biopsy and provide prioritized recommendations as well as identify patterns of responses for novel agents across different cancers. The comparison of drug sensitivity of an individual patient’s tumour cells across the developed pan-cancer drug sensitivity database allows assessment of patient and cancer specific drug responses. This method of identification of outlier drug responses examines the similarities and differences of individual patient’s drug sensitivity to the pan-cancer profile of a drug and highlights drugs with a patient specific effect. In combination with genetic profiling of the patient’s tumour cells, the drug response profile is then used as empirical evidence to support treatment decisions. The pan-cancer drug sensitivity comparison offers thus new insights in repurposing of targeted therapies and identification of commonalities of drug sensitivity patterns between rare cancers and the common types of cancers. Evidence from the methodology has already been used for development of n-of-1 style trials for patients with a particularly aggressive rare cancer, after the standard treatment options were exhausted.

Related Publications

Ex vivo analysis of DNA repait targeting in extreme rare cutaneous apocrine sweat gland carcinoma. Mäkelä R, Härmä V, Badra-Fajardo N, Wells G, Lygerou Z, Sangfelt O, Kononen J, Rantala JK.  Oncotarget. 2021.

Ex vivo assessment of targeted therapies in a rare metastatic epithelial-myoepithelial carcinoma. Mäkelä R, Arjonen A, Suryo Rahmanto A, Härmä V, Lehtiö J, Kuopio T, Helleday T, Sangfelt O, Kononen J, Rantala JK.  Neoplasia. 2020;22(9):390-398.

Ex vivo modelling of therapy efficacy for rare Krugenberg tumors – a report of two cases. Arjonen A, Mäkelä R, Virtakoivu R, Härmä V, Kuopio T, Hakkarainen H, Hollmén M, Kononen J, Rantala JK. Onc. Res. 2020;3(7).

Ex vivo modelling of drug efficacy in a rare metastatic urachal carcinoma. Mäkelä R, Arjonen A, Härmä V, Rintanen N, Paasonen L, Paprotka T, Rönsch K, Kuopio T, Kononen J, Rantala JK. BMC Cancer. 2020;20(1):590.

Image-based ex vivo drug screen to assess targeted therapies in recurrent thymoma. Arjonen A, Mäkelä R, Härmä V, Rintanen N, Kuopio T, Kononen J, Rantala JK.  Lung Cancer. 2020;145:27-32.

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