Molecular Profile Detail

Profile Name CDKN2A loss
Gene Variant Detail

CDKN2A loss (loss of function)

Relevant Treatment Approaches CDK Inhibitor (Pan) CDK4 Inhibitor CDK4/6 Inhibitor CDK6 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
CDKN2A loss pancreatic cancer decreased response CDK4/6 Inhibitor Palbociclib + Rigosertib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the efficacy of ON-01910 in pancreatic cancer cell lines with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss pancreatic cancer decreased response CDK4/6 Inhibitor GSK461364 + Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the efficacy of GSK461364 in pancreatic cancer cells with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss pancreatic cancer decreased response CDK4/6 Inhibitor Gemcitabine + Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the efficacy of Gemzar (gemcitabine) in pancreatic cancer cells with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss Advanced Solid Tumor predicted - sensitive PF-00477736 + PF3644022 Preclinical - Cell culture Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of multiple cancer cell lines harboring CDKN2A loss and in Cdkn2a-depleted transformed cells in culture (PMID: 26140595). 26140595
CDKN2A loss melanoma sensitive CDK Inhibitor (Pan) CDK4 Inhibitor CDK6 Inhibitor Alvocidib Preclinical Actionable In a preclinical study, melanoma cell lines with CDKN2A loss demonstrated a greater sensitivity to Alvocidib (flavopiridol) as compared to melanoma cell lines positive for CDKN2A (PMID: 12777976). 12777976
CDKN2A loss renal cell carcinoma sensitive CDK4/6 Inhibitor Palbociclib Preclinical Actionable In a preclinical study, renal cell carcinoma cell lines with CDKN2A loss were sensitive to Palbociclib (PD-0332991) (PMID: 23898052). 23898052
CDKN2A loss melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line with CDKN2A loss demonstrated sensitivity to Mekinist (trametinib) in culture, resulting in inhibition of cell growth (PMID: 27488531). 27488531
CDKN2A loss melanoma resistant CDK4/6 Inhibitor Palbociclib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line deficient for CDKN2A demonstrated resistance to treatment with Ibrance (palbociclib) in culture (PMID: 27488531). 27488531
CDKN2A loss brain glioblastoma multiforme sensitive CDK4 Inhibitor Milciclib Preclinical - Cell line xenograft Actionable In a preclinical study, Milciclib (PHA-848125AC) resulted in tumor regression in glioma cell line xenograft models with CDKN2A loss (PMID: 23347136). 23347136
CDKN2A loss neuroendocrine tumor sensitive CDK4 Inhibitor ZK 304709 Preclinical Actionable In a preclinical study, an orthotopic mouse model treated with ZK 304709 demonstrated an 80% tumor growth reduction in neuroendocrine tumor cells with CDKN2A loss (PMID: 18829975). 18829975
CDKN2A loss chordoma sensitive CDK4/6 Inhibitor Abemaciclib Preclinical - Cell culture Actionable In a preclinical study, Abemaciclib (LY2835219) inhibited growth of chordoma cell lines with CDKN2A loss and loss of p16 protein expression in culture (PMID: 26183925). 26183925
CDKN2A loss chordoma sensitive CDK4/6 Inhibitor Palbociclib Preclinical - Cell culture Actionable In a preclinical study, Ibrance (palbociclib) inhibited expression of phosphorylated Rb and growth of chordoma cell lines with CDKN2A loss and loss of p16 protein expression in culture (PMID: 26183925). 26183925
CDKN2A loss pancreatic cancer decreased response CDK4/6 Inhibitor HMN-214 + Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) antagonized the activity of HMN-214 in pancreatic cancer cell lines with CDKN2A loss in culture (PMID: 25156567). 25156567
CDKN2A loss non-small cell lung carcinoma sensitive CDK4/6 Inhibitor Palbociclib Phase II Actionable In a Phase II trial (TAPUR), Ibrance (palbociclib) treatment resulted in a disease control rate of 29% (7/28, 1 partial response, 6 stable disease at 16 weeks) in patients with non-small cell lung cancer harboring CDKN2A loss or mutations, with a median progression-free survival of 9.7 weeks and a median overall survival of 20.6 months (J Clin Oncol 37, 2019 (suppl; abstr 9041); NCT02693535). detail...
CDKN2A loss non-small cell lung carcinoma sensitive CDK4/6 Inhibitor Palbociclib Phase II Actionable In a Phase II trial, treatment with Ibrance (palbociclib) resulted in and stable disease in 50% (8/16) of non-small cell lung cancer patients with CDKN2A loss (J Clin Oncol 32:5s, 2014 (suppl; abstr 8077)). detail...
Clinical Trial Phase Therapies Title Recruitment Status
NCT02933736 Phase 0 Ribociclib Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients Unknown status
NCT02540876 Phase I ABT-348 Ilorasertib in Treating Patients With CDKN2A-deficient Advanced or Metastatic Solid Cancers That Cannot Be Removed by Surgery Completed
NCT03834740 Phase I Everolimus + Ribociclib Ph0/2 Ribociclib & Everolimus Recruiting
NCT02334527 Phase II Palbociclib Phase II Trial of Palbociclib (PD-0332991) in Patients With Metastatic Urothelial Cancer (UC) After Failure of First-Line Chemotherapy Terminated
NCT03435250 Phase I AG-270 Study of AG-270 in Subjects With Advanced Solid Tumors or Lymphoma With MTAP Loss Recruiting
NCT01711658 Phase II Cisplatin Cisplatin + Lapatinib TRYHARD: Radiation Therapy Plus Cisplatin With or Without Lapatinib in Treating Patients With Head and Neck Cancer Active, not recruiting
NCT02896335 Phase II Palbociclib Palbociclib In Progressive Brain Metastases Recruiting
NCT02693535 Phase II Cobimetinib + Vemurafenib Regorafenib Pembrolizumab Temsirolimus Dasatinib Pertuzumab + Trastuzumab Ipilimumab + Nivolumab Crizotinib Palbociclib Sunitinib Olaparib Cetuximab TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer Recruiting
NCT03220646 Phase II Abemaciclib The Purpose of This Study is to Test Any Good and Bad Effects of a Study Drug Called Abemaciclib (LY2835219) in Patients With Recurrent Brain Tumors. Recruiting