Precision Medicine of Osteosarcoma - Opportunity, Challenge and Practice

Jun. 12, 2015 Source:

Osteosarcoma is a disease with very complicated gene background. Its pathogenesis and the gene causing tumor to occur are still unknown today. Therefore, the basic research and progress of diagnosis & treatment of osteosarcoma face difficulties and challenges. Over the two decades, osteosarcoma is still treated by classic medicine, assisted with chemotherapy. In case of chemotherapy failure and high rate of lung metastasis, clinical doctors, lacking of new treatment methods, are always very passive.

    Due to the low morbidity, it's hard to conduct randomized controlled trial for osteosarcoma in a large scale. Thus, it moves slowly to change clinical practice based on medical evidence so as to improve the survival rate of patients.  In recent years, as the biomedicine based on gene sequencing experiences a rapid development,

especially in tumor field. Particular driver genes of many tumors or molecular markers related to treatment effect are found. Precision medicine is to customize the best treatment plan for each patient on the premise of gene sequencing and biological information analysis so as to maximize the treatment effect and minimize the side effect. Under such background, the precision medicine of osteosarcoma faces opportunities and challenges. It has good research and development prospect in the following direction.

1. Exploration and molecular classification of driver gene. The complex gene background of osteosarcoma means extensive and varied gene mutation spectrum driving tumor growth. The age of onset and histopathologic subtype may differ from one another. At present, it is proved by several relatively large scale of sequencing study. In the meantime, some widespread gene mutation is also explored such as p53 and PI3K related pathway. However, there is no more direct evidence to prove the above mutation or pathway will benefit the patients as therapeutic target. Specimen related to the medicine used needs to be further collected for in-depth study.

2. Accurate diagnosis and prognosis monitoring: Osteosarcoma has such a high metastasis that 80% of the patients will get micrometastasis. In this aspect, there are primary two clinical problems: 1) lack of highly precise and flexible indexes to detect micrometastasis; 2) the micrometastasis that fails to be killed by chemotherapy becomes the root cause of tumor recurrence and the drug-resistant mechanism is unclear. Therefore, it is of clinically significant to separate and study CTC of osteosarcoma. Though osteosarcoma lacks distinctive and clear surface markers, its CTC research gains ground, including the assorting process based on physical difference of cells and negative enrichment. In addition, the advancement of the study on detecting circulating tumor DNA (ctDNA) also provide a method to more accurately detect the curative effect of chemotherapy. It has a higher flexibility and lower detection cost compared to CTC. At last, ctDNA study and the in-depth sequencing study after CTC separation is significant for discovering the chemotherapy resistance and mechanism of pulmonary metastasis.

3. Patient derived xenograft (PDX):The effective rate of chemotherapy for osteosarcoma is between 60-70%. In view of chemotherapy resistance, the effective rate of the second- and third-line drugs are very limited. There isn't an uniform standard in clinical selection of second- and third-line drugs. For these problems, we may establish a PDX to monitor the sensibility of the chemotherapy drug and targeted drug by utilizing animal model. This is a method worthy of attempting for the purpose of improving chemotherapy efficiency. Moreover, PDX can also be used in new medicine research and development for osteosarcoma and related pathogenesis study. Thus, it is a very useful tool and method for the precision medicine of osteosarcoma.

Hua Yingqi, Doctor of Medicine, Director Assistant of Shanghai Bone Tumor Institute, selected into Class A of Shanghai Pujiang Talent Plan (2012) and "New, Excellent and Young" Talent Plan of Shanghai Municipal Commission of Health and Family Planning. Graduated from Shanghai Medical School of Fudan University in clinical medicine with Bachelor's degree in 2006, The Second Military Medical University with Doctor's degree and completed study of postdoctor in MD Anderson Cancer Center of University of Texas in 2011.