Medical Bulletin 23/December/2022

The KRAS protein is part of a normal signaling pathway regulating growth and proliferation of cells, but activating mutations in KRAS drives abnormal growth in cancer. KRAS mutations are especially common in pancreatic cancers, occurring in about 90% of patients, while KRAS G12C mutations are present in 1-2% of cases.

In the Phase I/II CodeBreaK 100 trial, the KRAS G12C inhibitor sotorasib achieved meaningful anticancer activity with an acceptable safety profile in heavily pretreated patients with KRAS G12C-mutated metastatic pancreatic cancer, according to researchers at The University of Texas MD Anderson Cancer Center.

Reference:

David S. Hong et al,Sotorasib in KRAS p.G12C–Mutated Advanced Pancreatic Cancer, New England Journal of Medicine

Breakthrough for Artemis-SCID patients in the form of Infant gene therapy

Gene correction has been used before in patients with other genetic forms of SCID, but its use in Artemis-SCID is significant because these patients usually respond more poorly to standard bone marrow transplants. Complications can include rejecting the marrow graft, graft-vs.-host disease - in which the donor T cells attack the recipient's tissues - chronic infections leading to organ damage, stunted growth, and premature death.

Ten young children born without functioning immune systems and lacking the ability to fight infections are on track for healthier lives thanks to a new gene therapy treatment pioneered at UC San Francisco, reports a Dec. 22 study in the New England Journal of Medicine.

Reference:

Mort Cowan et al, UNIVERSITY OF CALIFORNIA - SAN FRANCISCO,JOURNAL New England Journal of Medicine

People with hand osteoarthritis may benefit from talarozole

More than 40% of individuals will develop osteoarthritis (OA) during their lifetime. Hand (OA) is an extremely common form of OA and there are currently no disease modifying treatments that effectively relieve symptoms or stop deformity and stiffness of the joints.

Tonia Vincent, Professor of Musculoskeletal Biology & Honorary Rheumatologist at Oxford's Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), said: 'Hand osteoarthritis is a common and debilitating medical condition that affects mainly women, especially around the time of the menopause. We currently have no effective treatments that modify their disease.'

Reference:

Tonia Vincent et al, Variants in ALDH1A2[Q1] reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis ,JOURNAL Science Translational Medicine.