Personal Genome Diagnostics Inc. — Department of Health and Human Services SBIR Phase I: NCI

Description

DESCRIPTION provided by applicant With over million new cases and over deaths annually colorectal cancer CRC is the third most common cancer and the third highest cause of cancer death in the developed world CRC patients are classified into stage I through IV depending on the extent of their disease Approximately of CRC patients are diagnosed with localized stage II cancer amounting to new cases in the developed world and in the U S annually The standard of care for stage II CRC includes surgical removal of the tumor followed by adjuvant therapy in high risk patients The current risk stratification approaches including the standard of care TNM staging method offer only limited accuracy as evidenced by the approximately of stage II CRC patients who recur with predominantly incurable disease and do not receive adjuvant therapy Therefore novel more accurate approaches to identify high risk patients are urgently needed Circulating cell free tumor derived DNA ctDNA is released by tumors and carries tumor exclusive genetic alterations Hypothesis We hypothesize that direct and early detection of minimal residual disease MRD using ctDNA will more accurately identify high risk CRC patients than the current approaches that predict recurrence based on analyses of the resected tumors Preliminary Data We have pioneered the development of technologies for evaluation of ctDNA and established ctDNA as an exquisitely specific and sensitive marker for tumor burden and MRD Most relevant to this proposal we have demonstrated that andgt of localized CRC release detectable ctDNA and that post surgery ctDNA levels are prognostic Specific Aims In this phase I SBIR we propose to develop and validate CRCDetect a molecular test for the detection of MRD using ctDNA in the peripheral blood of stage II CRC patients collected weeks after surgery CRCDetect can identify patients who are not cured by surgery alone have a high risk of recurrence and may benefit from adjuvant therapy In Specific Aims and we will focus on the development and analytical validation of CRCDetect In Specific Aim we will evaluate the prognostic performance of CRCDetect in a cohort of stage II CRC patients Overall Impact Together these studies will demonstrate the feasibility of using CRCDetect to detect MRD in early stage CRC patients from a simple blood draw after surgery thereby identifying the stage II CRC patients with a high risk of recurrence and informing whether a patient should receive adjuvant treatment PUBLIC HEALTH RELEVANCE Colorectal cancer CRC is the third most common cancer with over new cases diagnosed and deaths predicted in in the United States More than of CRC patients including stage I III and some stage IV patients have surgery performed intended to cure their cancer Current standard care for stage II CRC includes surgical removal of tumor followed by chemotherapy treatment for patients who have a high risk of recurrence Although existing approaches attempt to predict the risk of recurrence based on features of the resected tumors they achieve only modest accuracy as evidenced by cancer recurrence in stage II CRC patients Given the high specificity and sensitivity of circulating tumor DNA ctDNA as a cancer marker we propose to develop and validate CRCDetect a non invasive approach for detection of cancer specific mutations in peripheral blood of CRC patients using digital sequencing and polymerase chain reaction PCR methods CRCDetect would identify from a simple blood drawl the stage II CRC patients who have a high recurrence risk and may benefit from chemotherapy The results from CRCDetect would enable physicians to determine the most appropriate treatment course for stage II CRC patients and would improve the outcome and survival of this patient cohort