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Gene | CDKN2A |
Variant | loss |
Impact List | unknown |
Protein Effect | loss of function |
Gene Variant Descriptions | CDKN2A loss indicates loss of the CDKN2A gene, mRNA and protein. |
Associated Drug Resistance | |
Category Variants Paths |
CDKN2A mutant CDKN2A inact mut CDKN2A loss |
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 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 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 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 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 |