MIRPLA-KIT: Method to identify cancer patients with platinum resistant disease and related kit
Dr Gustavo Baldassarre, National Cancer Institute CRO Aviano; Dr Maura Sonego, National Cancer Institute CRO Aviano
National Cancer Institute CRO Aviano
The identification of cancer patients potentially treatable with platinum that may respond poorly to chemotherapy and/or that might merit a different treatment is a cogent unmet clinical need. In fact platinum agents are used in 80% of clinical anticancer regimens, but unfortunately the development of platinum-resistant tumor recurrences represents a very frequent event. Moreover costs for platinum based regimens can be higher than those for platinum free regimens. By using the presented genetic biomarker, patient eligible for platinum therapy at higher risk of developing drug resistance and disease progression could have the opportunity to receive a more specific anticancer treatment. In this context, a platinum sensitivity biomarker is economically and clinically relevant.
The proposed biomarker for platinum sensitivity is a 10-gene signature identified in primary Ovarian Cancer (OC) cell lines for which the genetic profile was available. Results show that the 10-gene signature segregates OC patients with worse PFS and OS. The signature was verified in silico on two more cancer type: triple-negative breast cancer (TNBC) that is considered a platinum sensitive tumor, and estrogen receptor–positive ((ER+) BC). Results showed that the 10-gene signature was able to predict PFS in TNBC, but not (ER+) BC, confirming its the ability to identify patients eligible for platinum therapy at higher risk of developing drug resistance and disease progression.
If we only refer to new cancer cases, based on the currently available therapeutic options for each cancer type based on international guidelines, in EU about 1.000.000 of patients will be likely treated with a combination therapy that include either cisplatin or carboplatin and about 400.000 with a regimen based on the use of oxaliplatin (i.e. colorectal, gastric and esophagus cancer patients).The kit could be used as support tool for clinicians to select cancer treatment. RNA quantification can be performed with any of the available techniques for nucleic acids quantification. The kit can be proposed on the market as e.g. NGS/RT-PCR kit including necessary reagents and combined with one or more instruments. The final user of the predictive kit can be hospitals or external facilities.
Preliminary tests to evaluate the signature biomarker properties were performed using a customized statistical analysis method applied to the expression profiles available online in the KM plotter dataset for 614 OC patients, 161 TNBC patients and 762 (ER+) BC patients. The protocol for gene expression analysis has already been developed and validated on cell lines. The kit validation on real samples is planned within the Proof of Concept program that was recently assigned to CRO. The signature will be tested on 200 epithelial ovarian cancer samples in first instance and validated on a larger cohort afterwards. Researchers will have the possibility to test the signature on more than 1000 samples in large part already available. The inventors have deep knowledge in oncology field and biochemical techniques and they also developed cancer cell lines models.
The priority Italian patent, filed in 2019, has been granted.
- Sonego et al., " USP1 links platinum resistance to cancer cell dissemination by regulating Snail Stability", Sci. Adv. 8: 5(5), eaav3235 (2019) (DOI: 10.1126/sciadv.aav3235) .