CDK6 amplification

Palbociclib showed limited activity in histology-agnostic CDK4- or CDK6-amplified tumors, though CNS tumors may be worthy of future investigation.

Overall, while the pediatric and adult pHGG have similar outcomes, there are differences in their genomic structures, most notably in adult pHGG harboring a higher SCNA load. Overall, pHGG represent a biologically diverse set of clinically aggressive tumors that warrant further intensive study.

Through our analysis, we were able to identify molecular features characteristic of DMG and DHG. By identifying the recurrent co-mutations including actionable FGFR1 point mutations found in nearly one-third of H3K27M-mutant DMG in young adults, our findings can inform clinical translational studies, patient diagnosis, and clinical trial design.

Moreover, invasion depth was an independent factor for ESCC prognosis. Taken together, for ESCC patients in III-IV stage, CDK6 amplification indicated a better prognosis.

Our study compared the mutational characteristics of gliomas with CDK4/6 alterations and demonstrated the potential prognostic value of CDK6 amplification, and provide the new basis of precise diagnosis and treatment in gliomas.

This single arm, multicentre Phase II evaluated the efficacy of abemaciclib (200mg/d orally BID) in molecularly-selected, HPV negative (HPV-), RM-HNSCC patients (pts) progressing after at least 1 prior line of platinum and cetuximab. Abemaciclib had limited antitumor activity in RM-HNSCC harboring molecular alteration in CDK4/6 pathway. Clinical trial information: NCT03356223.

Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway, KRAS/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M-mutant spinal cord diffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management.

Selective CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, have been approved in combination with hormone therapy for the treatment of patients with HR+, HER2-negative advanced or metastatic breast cancer (mBC). Identifying the different mechanisms by which resistance to CDK4/6 inhibitors occurs may help to design new treatment strategies to improve patient outcomes. This review presents the currently available knowledge on the mechanisms of resistance to CDK4/6 inhibitors, explores possible treatment strategies that could overcome this therapeutic problem, and summarizes relevant recent clinical trials.

Recent WHO (2021) guidelines stratified MB into four molecular subgroups with four and eight further subgroups for SHH and non-WNT/non-SHH MB, respectively. In this review, we discuss advancements in genetics, epigenetics, and transcriptomics for better characterization, prognostication, and treatment of MB using precision medicine.

The most common assignable treatment arms were Z1B/Z1BX1 (palbociclib with CCND1/2/3, N = 13), Z1F (copanlisib with PIK3CA Mutations, N = 13), S1/S1X1 (trametinib with NF1 mutation, N = 12), and Z1C/Z1CX1 (palbociclib with CDK4/CDK6 Amplification and Rb Expression by IHC, N = 10). Variants observed in the blood are consistent with what is reported in the tissue. Using liquid biopsy when tissue is not evaluable can expand the ability of patients to obtain mutation information that can inform treatment compared to using tumor tissue only. Cell-free DNA provided valuable mutation information for these patients and could have resulted in up to an additional 75 patients being eligible for treatment selection based on their mutation profile.

P, Available, Novartis Pharmaceuticals

We further report novel co-amplifications of various oncogenes, which may have therapeutic implications. Finally, the genetic and epigenetic concordance of ISAs and UPS of the left atrium further supports a shared pathogenesis and common classification.

Our study provided a characteristic of CDK4/6 amplification in Chinese and Western pan-cancer patients . Analysis revealed frequent CDK4/6 amplification in lung cancer, sarcoma, stomach carcinoma, ovarian carcinoma and liver cancer . It is suggested patient with these cancer types may potentially benefit from CDK4/6 inhibitor.

Although ctDNA exhibited similar utility to tissue biopsies, more mutations in targetable genes were missed in tissue biopsies. Therefore, the evaluation of ctDNA in conjunction with tissue biopsies may help to detect additional targetable mutations to improve clinical outcomes in advanced NSCLC.