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Novel Screening Biomarkers for Muscle Invasive Bladder Cancer Response to Chemotherapy
Muscle Invasive Bladder Cancer (MIBC) is an aggressive and metastatic tumor which accounts for 30% of all bladder cancer cases. Currently, the standard of care for such patients remains cystectomy, preceded by neoadjuvant chemotherapy (AMVAC-methotrexate, vinblastine, doxorubicin and cisplatin). The combination of both surgery and chemotherapy has a significant impact of the quality of life of MIBC patients. Hence, if either treatment can be avoided, it will greatly help improve the quality of life for patients. While surgery is requisite in MIBC cases, the benefits of neoadjuvant chemotherapy remain to be evaluated. Current data suggests that only 28-38% MIBC patients achieve pathologic complete response (pT0). Further, pT0 leads to cure in 90% of MIBC cases. Yet, the patients who do not achieve pT0 still show cure 50% of times post-surgery. Thus, there is no clear pattern that brings out the benefits of chemotherapy in MIBC patients prior surgery using the current methods to evaluate response. Hence, there is an urgent need to develop novel screening biomarkers that will predict the likelihood of chemotherapy response in MIBC patients. This will also enable physicians with tools to tailor a treatment regimen for the patient, and potentially avoid chemotherapy if they are unlikely to gain benefit from it. In the era of personalized medicine, gaining additional genetic information from MIBC cases will also help predict potential targeted therapies for patients, outside of the standard of care chemotherapy.
Summary of Invention
Dr. Plimack and her team at Fox Chase Cancer Center have devised a novel screening algorithm that can distinguish MIBC patients that are likely to respond to the AMVAC regimen compared to those who will not. By sequencing bladder tumors from patients that had received AMVAC regimen prior surgery, the researchers have identified at least three key genes that are key in determining response to AMVAC. Mutations or other genetic alterations in the identified genes has been correlated to better AMVAC response. All three genes are crucial bystanders in the DNA damage response (DDR) pathway. Thus, defects in these genes might serve as proxy for the DDR machinery and confer sensitivity to chemotherapy. The key novelty is that the genes identified have not been associated with AMVAC response prior to this study. Further, the success story of PARP inhibitors such as Olaparib in BRCA1/2 defective tumors shows that identifying tumor specific defects in DDR can have long term and potentially curative implications in patients. On similar lines, the study by Dr. Plimack and her team lays the groundwork for novel screening methods for MIBC patients for chemotherapy response. The study will truly help change the quality of life for such patients and save valuable time for patients prior to surgery.
Patent Status: Patent pending
For Licensing/Partnering discussion, please contact:
Inna Khartchenko, MS, MBA
Director, Technology Transfer Fox Chase Cancer Center