iPSC-Derived Organoids as Therapeutic Models in Regenerative Medicine and Oncology

Progress made during the last decade in stem cell biology allows currently an unprecedented potential to translate these advances into the clinical applications and to shape the future of regenerative medicine. Organoid technology is amongst these major developments, derived from primary tissues or more recently, from induced pluripotent stem cells (iPSC). The use of iPSC technology offers the possibility of cancer modeling especially in hereditary cancers with germline oncogenic mutations. Similarly, it has the advantage to be amenable to genome editing with introduction of specific oncogenic alterations using CRISPR-mediated gene editing. In the field of regenerative medicine, iPSC-derived organoids hold promise for the generation of future advanced therapeutic medicinal products (ATMP) for organ repair. Finally, it appears that they can be of highly useful experimental tools to determine cell targets of SARS-Cov-2 infections allowing to test anti-Covid drugs. Thus, with the possibilities of genomic editing and the development of new protocols for differentiation toward functional tissues, it is expected that iPSC-derived organoid technology will represent also a therapeutic tool in all areas of medicine.

Cancer Cell Therapy: Looking to the Future of CAR T Cell Manufacturing (Vol. 25, No. 8, Full Issue)

For the month of August 2021, APBN looks at some of the progress made in cancer research. In Features, we have Yie Hou Lee and Michael Birnbaum from the Singapore-MIT Alliance for Research and Technology Critical Analytics for Manufacturing Personalized-Medicine (SMART-CAMP) to share about the future of CAR T cell manufacturing. Next, a team of researchers from the National Neuroscience Institute, National University of Singapore, and the Duke-NUS Medical School enlightens us on the difficulty of treating glioblastoma brain tumours and how they plan to address its critical issues. Then we have Dr. Chi-Jui Liu and Hsiao Yun Lu to talk about hereditary cancers and how we may improve our odds in this game of roulette. In Columns, we have an analysis by Dr. Ping-Chung Leung on the integrative use of Traditional Chinese Medicine in managing treatment outcomes of COVID-19 patients and a reflection by Dr. Chris Nave on the lessons we can take away from the development of COVID-19 vaccines. Finally, in Spotlights, we share highlights from the Vaccines World Summit 2021 and an interview with Mr. Abel Ang, Group Chief Executive of Advanced MedTech on how their new venture AbAsia Biolabs can help meet Singapore’ need for increased COVID-19 test kits as we enter a new normal.

Patient and Family Preferences on Health System-Led Direct Contact for Cascade Screening

Health benefits to relatives of people at known genetic risk for hereditary cancer syndromes is key to realizing the promise of precision medicine. We conducted a qualitative study to design a patient- and family-centered program for direct contact of relatives to recommend cascade genetic testing. We conducted two rounds of data collection using focus groups followed by individual interviews with patients with HBOC or Lynch syndrome and a separate sample of people with a family history of hereditary cancers. Results indicate that U.S.-based health system-led direct contact of relatives is acceptable to patients and families, should take a programmatic approach, include consent of relatives before proband testing, complement to existing patient-mediated disclosure, and allow for relative control of information. Our findings suggest a set of requirements for U.S.-based direct contact programs that could ultimately benefit more relatives than current approaches.

The disease sites of female genital cancers of BRCA1/2-associated hereditary breast and ovarian cancer: a retrospective study

Disease sites of female genital tract cancers of BRCA1/2-associated hereditary breast and ovarian cancer (HBOC) are less understood than non-hereditary cancers. We aimed to elucidate the disease site distribution of genital cancers in women with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+) of HBOC. For the primary disease site, the proportion of fallopian tube and peritoneal cancer was significantly higher in BRCA2+ (40.5%) compared with BRCA1+ (15.4%) and BRCA− (no pathogenic variant, 12.8%). For the metastatic site, the proportion of peritoneal dissemination was significantly higher in BRCA1+ (71.9%) than BRCA− (55.1%) and not different from BRCA2+ (71.4%). With one of the most extensive patients, this study supported the previous reports showing that the pathogenic variants of BRCA1/2 were involved in the female genitalia’s disease sites.

Gut Microbial Signatures in Sporadic and Hereditary Colorectal Cancer

Colorectal cancer (CRC) is the fourth most common cause of cancer-related death and the third most common cancer in the world. Depending on the origin of the mutation, colorectal carcinomas are classified as sporadic or hereditary. Cancers derived from mutations appearing during life, affecting individual cells and their descendants, are called sporadic and account for almost 95% of the CRCs. Less than 5% of CRC cases result from constitutional mutations conferring a very high risk of developing cancer. Screening for hereditary-related cancers is offered to individuals at risk for hereditary CRC, who have either not undergone genetic evaluation or have uncertain genetic test results. In this review, we briefly summarize the main findings on the correlation between sporadic CRC and the gut microbiota, and we specifically focus on the few evidences about the role that gut microorganisms have on the development of CRC hereditary syndromes. The characterization of a gut microbiota associated with an increased risk of developing CRC could have a profound impact for prevention purposes. We also discuss the potential role of the gut microbiota as therapeutic treatment.