TP53 deletion

Here, we report a case of an ALK-positive lung adenocarcinoma patient who developed resistance following sequential treatment with the ALK-TKI alectinib and lorlatinib, accompanied by histological transformation to LCNEC and concurrent genetic alterations including TP53 deletion, CDKN2A deletion, and MYC amplification. This case expands the spectrum of ALK-TKI resistance mechanisms and highlights the potential value of exploring combinatorial approaches incorporating immunotherapy, antiangiogenic therapy, and chemotherapy for the management of such cases.

An improved diagnostic algorithm based on the combined use of FISH and NGS methods makes it possible to increase the accuracy of identification of genetic subtypes of aggressive B-cell lymphomas in children. This helps to categorize the diagnosis based on the molecular and genetic characteristics of the tumor, paving the way for improved prognosis and treatment effectiveness.

These data demonstrate the role of PDLIM2 in suppressing lung adenocarcinoma metastasis, thereby improving our understanding of this crucial tumor suppressor and lung cancer. They also provide a useful model for studying metastasis and testing new lung cancer treatments in vivo .

Based on this, we infer that the patients with a normal SFLC ratio are enriched with non-high-risk features and behave less aggressively.

P1/2, N=73, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

Future studies should explore long-term durability beyond 5 years and validate MRD thresholds for treatment cessation. National Nature Science Foundation of China, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Beijing Xisike Clinical Oncology Research Foundation.

P2, N=235, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

High-throughput drug screening identifies FK228 and thioguanine as promising therapeutic candidates, both of which show in vivo efficacy and are validated in PTEN-deleted organoids. Together, these results establish MEPP as a platform for studying PTEN-deleted ovarian cancer and provide a strategy for generating clinically relevant tumor models through targeted gene editing.

In conclusion, CAR-T cell therapy targeting GPRC5D is highly effective and well-tolerated in patients with RRMM, especially those with high-risk factors. Further studies with larger cohorts and longer follow-up periods are needed to validate the clinical application of GPRC5D-targeted CAR-T cell therapy in RRMM, particularly for patients who have failed BCMA-targeted therapies.

Post-hoc analysis of the OCEAN trial melflufen-treated del(17p) patient population also demonstrated favorable progression free survival compared to pomalidomide-treated cohort. Our insights into the molecular mechanisms of melflufen activity in TP53-/- myeloma support its clinical efficacy and application in the del(17p) and TP53-/- patient population.Trial registration NCT03151811, registration 2017-05-09.

Autologous CD19 CAR T cells were infused after lymphodepletion chemotherapy with cyclophosphamide and fludarabine. Sequential administration of CAR20/22/19 T cells may have reduced the antigen escape relapse in DLBCL. For patients with DLBCL relapse after allo-HSCT, larger trials are required to validate the safety and effectiveness of pseudoallogeneic CAR-T therapy as well as its ability to lower the rate of antigen escape relapse.

A notable feature of the HRS-like cells in this case is the gain of markers associated with CHL, such as CD30 and CD15. This immunophenotypic shift highlights the concept of lymphoma plasticity, where the tumor cells evolve in response to selective pressures, such as CAR T cell therapy.