Molecular Profile Detail

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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 Therapy Name Approval Status Evidence Type Efficacy Evidence References
CDKN2A loss NRAS mut melanoma predicted - sensitive Abemaciclib Case Reports/Case Series Actionable In a Phase I trial, Verzenio (abemaciclib) resulted in a partial response in a melanoma patient with CDKN2A loss and NRAS mutation (PMID: 27217383). 27217383
CDKN2A loss NRAS Q61K melanoma sensitive Palbociclib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Mekinist (trametinib) induced tumor regression in a mouse melanoma model expressing NRAS Q61K and harboring CDKN2A loss (PMID: 22983396). 22983396
CDKN2A loss NRAS Q61K melanoma sensitive SBI-0640756 Preclinical Actionable In a preclinical study, SBI-0640756 delayed tumor growth of melanomas in mice with a genetic background of NRAS Q61K and CDKN2A loss (PMID: 26603897). 26603897
CDKN2A loss PIK3CA act mut lung squamous cell carcinoma predicted - sensitive Buparlisib + Palbociclib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Buparlisib (BYL719) and Ibrance (palbociclib) resulted in increased tumor growth inhibition compared to either agent alone in patient-derived xenograft (PDX) models of lung squamous cell carcinoma harboring PIK3CA E542K or E545K mutations with p16 (CDKN2A) loss, including models that also had either PIK3CA amplification or PTEN loss (PMID: 30093452). 30093452
CDKN2A loss PIK3CA E545K PIK3CA amp lung squamous cell carcinoma sensitive Buparlisib + Palbociclib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Buparlisib (BYL719) and Ibrance (palbociclib) resulted in increased tumor growth inhibition compared to either agent alone in patient-derived xenograft (PDX) models of lung squamous cell carcinoma harboring PIK3CA E545K and PIK3CA amplification, with p16 (CDKN2A) loss (PMID: 30093452). 30093452
CDKN2A loss PIK3CA E542K PTEN loss lung squamous cell carcinoma sensitive Buparlisib + Palbociclib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Buparlisib (BYL719) and Ibrance (palbociclib) resulted in increased tumor growth inhibition compared to either agent alone in a patient-derived xenograft (PDX) model of lung squamous cell carcinoma harboring PIK3CA E542K and PTEN loss, with p16 (CDKN2A) loss (PMID: 30093452). 30093452
CDKN2A loss PIK3CA E542K PIK3CA amp lung squamous cell carcinoma sensitive Buparlisib + Palbociclib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Buparlisib (BYL719) and Ibrance (palbociclib) resulted in increased tumor growth inhibition compared to either agent alone in a patient-derived xenograft (PDX) model of lung squamous cell carcinoma harboring PIK3CA E542K and PIK3CA amplification, with p16 (CDKN2A) loss (PMID: 30093452). 30093452
BRAF V600E/K CDKN2A loss RB1 pos melanoma predicted - sensitive Palbociclib + Vemurafenib Phase Ib/II Actionable In a phase I/II trial, Ibrance (palbociclib) plus Zelboraf (vemurafenib) was safe and resulted in an overall response rate (ORR) of 26.7% (4/15), disease control rate (DCR) of 80% (12/15), and progression-free survival (PFS) of 2.8 mo in metastatic melanoma patients with prior BRAF inhibitor treatment and BRAF V600E/K, CDKN2A loss, and RB1 expression, and an ORR of 27.8% (5/18), DCR of 83.3% (10/18) and 2.8 mo PFS when combined with pts without prior BRAF inhibitor treatment (PMID: 33947696; NCT02202200). 33947696
BRAF V600E CDKN2A loss CHEK2 dec exp RB1 pos melanoma predicted - resistant Palbociclib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Ibrance (palbociclib) and Zelboraf (vemurafenib) combination therapy in a melanoma cell line harboring BRAF V600E, CDKN2A loss, RB1 expression, and decreased expression of CHEK2 via siRNA resulted in increased cell proliferation and p-ERK levels compared to treated cells without decreased expression of CHEK2 in culture (PMID: 33947696). 33947696
BRAF V600E CDKN2A loss NRAS Q61K melanoma predicted - resistant Cobimetinib + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring BRAF V600E and NRAS Q61K experienced progressive disease after a response to combination therapy with Zelboraf (vemurafenib) and Cotellic (cobimetinib), land was found to have acquired loss of CDKN2A (PMID: 34376578). 34376578
BRAF V600E CDKN2A loss NRAS G12V melanoma predicted - resistant Cobimetinib + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring BRAF V600E experienced progressive disease after a response to combination therapy with Zelboraf (vemurafenib) and Cotellic (cobimetinib), likely due to acquisition of NRAS G12V and a loss of one copy of CDKN2A (PMID: 34376578). 34376578
BRAF V600E CDKN2A loss NRAS G12V melanoma predicted - sensitive Palbociclib + Trametinib Preclinical - Pdx Actionable In a preclinical study, combination treatment with Ibrance (palbociclib) and Mekinist (trametinib) led to inhibition of tumor growth in a patient-derived xenograft (PDX) model of melanoma harboring BRAF V600E, NRAS G12V, and CDKN2A copy number loss (PMID: 34376578). 34376578
BRAF V600E CDKN2A loss NRAS G12V melanoma predicted - sensitive Palbociclib + Ulixertinib Preclinical - Pdx Actionable In a preclinical study, combination treatment with Ibrance (palbociclib) and Ulixertinib (BVD-523) led to inhibition of tumor growth in a patient-derived xenograft (PDX) model of melanoma harboring BRAF V600E, NRAS G12V, and CDKN2A copy number loss (PMID: 34376578). 34376578