Details of Disease

General Information of Disease (ID: DISR1RC5)

• Disease Name: Actinic keratosis
• Synonyms: senile keratosis; Senile hyperkeratosis; Senile keratosis; SK - solar keratosis; actinic keratosis (disease); actinic keratosis; actinic (solar) keratosis; solar keratosis
• Disease Class: EK90: Epidermal dysplasias
• Definition: A precancerous lesion of the skin composed of atypical keratinocytes. It is characterized by the presence of thick, scaly patches of skin. Several histologic variants have been described, including atrophic, acantholytic, and hyperkeratotic variants.
• Disease Hierarchy:
  DIS16DDV: Skin neoplasm
  DISJMUS4: Pre-malignant neoplasm
  DISR1RC5: Actinic keratosis
• ICD Code:
  ICD-11: ICD-11: EK90.0
  ICD-10: ICD-10: L57.0
  ICD-9: ICD-9: 702
  Expand ICD-11: 'EK90.0
  Expand ICD-10: 'L57.0
  Expand ICD-9: 702
• Disease Identifiers:
  MONDO ID: MONDO_0005173
  UMLS CUI: C0022602
  MedGen ID: 9627
  HPO ID: HP:0025127
  SNOMED CT ID: 201101007

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 4 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Aminolevulinic acid hci	DMS4BLQ	Approved	Small molecular drug	[1]
Aminolevulinic Acid Hydrochloride	DMWNHPC	Approved	Small molecular drug	[1]
Ingenol mebutate	DMK1CZJ	Approved	Small molecular drug	[2]
Tirbanibulin	DMJNV4O	Approved	Small molecular drug	[3]

This Disease is Treated as An Indication in 13 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
AK04	DMU7K86	Phase 3	Bispecific antibody	[4]
GDC 695	DMU5BYP	Phase 3	NA	[5]
KX-01	DMF0NA9	Phase 3	NA	[5]
LEO 43204	DMKMCP8	Phase 3	NA	[5]
SR-T100	DMIJY3F	Phase 3	NA	[6]
DFD-07	DMX4XCD	Phase 2/3	NA	[5]
AM-001	DMGVQI8	Phase 2	NA	[5]
AM001	DM9UMSJ	Phase 2	Small molecular drug	[7]
LFX453	DM2N5W6	Phase 2	NA	[5]
NanoPac	DM0TD4G	Phase 2	NA	[5]
Resiquimod	DML6XSP	Phase 2	Small molecular drug	[8]
VDA-1102	DMAJ85O	Phase 2	NA	[5]
SDZ-LAV-694	DM8SINB	Phase 1	NA	[9]

This Disease is Treated as An Indication in 1 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ATX-201	DMWJ245	Discontinued in Phase 2	NA	[10]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PLD2	TTRLMKF	moderate	Altered Expression	[11]
MC1R	TT0MV2T	Strong	Genetic Variation	[12]
MLANA	TT362RB	Strong	Biomarker	[13]
PPP5C	TTTW7FJ	Strong	Biomarker	[14]
PPT1	TTSQC14	Strong	Biomarker	[14]
RPS6KA5	TTYXEPL	Strong	Altered Expression	[15]
SSTR1	TTIND6G	Strong	Genetic Variation	[16]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC24A4	DTQWF14	Strong	Biomarker	[12]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
AK2	DEY1FJO	Strong	Biomarker	[17]

This Disease Is Related to 15 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CLDN11	OTNN6UTL	Limited	Biomarker	[18]
INPP5A	OT9CMGMS	Limited	Biomarker	[19]
KNSTRN	OTYA7UXS	Limited	Genetic Variation	[20]
KRT16	OTGA0EQN	Limited	Altered Expression	[21]
KRT72	OTAXW63A	Limited	Biomarker	[21]
TMC8	OTUAD95X	moderate	Genetic Variation	[22]
AK3	OTM59ZGG	Strong	Genetic Variation	[23]
AK4	OTA0T02Q	Strong	Genetic Variation	[23]
CCL27	OTUZYC61	Strong	Biomarker	[24]
COL17A1	OTID5AH2	Strong	Altered Expression	[25]
ENDOV	OTX2GXXX	Strong	Biomarker	[26]
HOXC4	OT52VJ6V	Strong	Altered Expression	[27]
IVL	OT4VPNGY	Strong	Altered Expression	[28]
MAL	OTBM30SW	Strong	Biomarker	[29]
SMIM10L2B	OT04IG2N	Strong	Biomarker	[30]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7443).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [4] ClinicalTrials.gov (NCT00308867) Photodynamic Therapy With PD P 506 A or Its Placebo Compared With Cryosurgery for the Treatment of Mild to Moderate Actinic Keratosis. U.S.National Institutes of Health.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] ClinicalTrials.gov (NCT01493921) Efficacy Study & Safety Evaluation of SR-T100 Gel in Actinic Keratosis Treatment. U.S. National Institutes of Health.
• [7] ClinicalTrials.gov (NCT03210740) Safety and Efficacy Study of AM001 Cream in the Treatment of Actinic Keratosis. U.S. National Institutes of Health.
• [8] ClinicalTrials.gov (NCT01583816) Dose-finding, Safety, Efficacy Trial of Topical Resiquimod in Patients With Multiple Actinic Keratosis Lesions. U.S. National Institutes of Health.
• [9] Recent patents reveal microtubules as persistent promising target for novel drug development for cancers. Recent Pat Antiinfect Drug Discov. 2009 Nov;4(3):164-82.
• [10] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026557)
• [11] AQP3 small interfering RNA and PLD2 small interfering RNA inhibit the proliferation and promote the apoptosis of squamous cell carcinoma.Mol Med Rep. 2017 Aug;16(2):1964-1972. doi: 10.3892/mmr.2017.6847. Epub 2017 Jun 23.
• [12] Pigmentation-Independent Susceptibility Loci for Actinic Keratosis Highlighted by Compound Heterozygosity Analysis.J Invest Dermatol. 2017 Jan;137(1):77-84. doi: 10.1016/j.jid.2016.09.007. Epub 2016 Sep 16.
• [13] Immunohistochemistry of pigmented actinic keratoses, actinic keratoses, melanomas in situ and solar lentigines with Melan-A.J Cutan Pathol. 2008 Oct;35(10):931-4. doi: 10.1111/j.1600-0560.2007.00921.x. Epub 2008 May 20.
• [14] Photodynamic therapy using intense pulsed light for treating actinic keratoses and photoaged skin of the dorsal hands: a randomized placebo-controlled study.Br J Dermatol. 2017 Feb;176(2):352-362. doi: 10.1111/bjd.14970. Epub 2016 Dec 28.
• [15] Astragalin Attenuates UVB Radiation-induced Actinic Keratosis Formation.Anticancer Agents Med Chem. 2018;18(7):1001-1008. doi: 10.2174/1871520618666171229190835.
• [16] Association analysis of somatostatin receptor (SSTR1 and SSTR2) polymorphisms in breast cancer and solar keratosis.Cancer Lett. 2001 May 26;166(2):193-7. doi: 10.1016/s0304-3835(01)00442-6.
• [17] Cutaneous squamous cell carcinomas are associated with basal proliferating actinic keratoses.Br J Dermatol. 2019 Apr;180(4):916-921. doi: 10.1111/bjd.16536. Epub 2018 Jun 29.
• [18] Expression of claudin-11 by tumor cells in cutaneous squamous cell carcinoma is dependent on the activity of p38.Exp Dermatol. 2017 Sep;26(9):771-777. doi: 10.1111/exd.13278. Epub 2017 Apr 10.
• [19] Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma.J Am Acad Dermatol. 2020 Apr;82(4):846-853. doi: 10.1016/j.jaad.2019.08.027. Epub 2019 Aug 19.
• [20] Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma.J Eur Acad Dermatol Venereol. 2019 Aug;33(8):1535-1540. doi: 10.1111/jdv.15615. Epub 2019 May 8.
• [21] Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients.BMC Cancer. 2013 Feb 5;13:58. doi: 10.1186/1471-2407-13-58.
• [22] Possible association between actinic keratosis and the rs7208422 (c.917AT, p.N306l) polymorphism of the EVER2 gene in patients without epidermodysplasia verruciformis.Clin Exp Dermatol. 2015 Apr;40(3):318-23. doi: 10.1111/ced.12506. Epub 2014 Dec 12.
• [23] Evaluation of two histological classifications for actinic keratoses - PRO classification scored highest inter-rater reliability.J Eur Acad Dermatol Venereol. 2019 Jun;33(6):1092-1097. doi: 10.1111/jdv.15580. Epub 2019 Apr 3.
• [24] Peptidase inhibitor 3 and chemokine ligand 27 may serve as biomarkers for actinic keratoses in organ transplant recipients.Eur J Dermatol. 2019 Jun 1;29(3):259-267. doi: 10.1684/ejd.2019.3559.
• [25] Aberrant expression of a hemidesmosomal protein, bullous pemphigoid antigen 2, in human squamous cell carcinoma.Lab Invest. 1996 Oct;75(4):589-600.
• [26] DNA repair, immunosuppression, and skin cancer.Cutis. 2004 Nov;74(5 Suppl):10-3.
• [27] Expression of the homeobox gene HOXC4 in keratinocytes of normal skin and epithelial skin tumors is correlated with differentiation.J Invest Dermatol. 1994 Sep;103(3):341-6. doi: 10.1111/1523-1747.ep12394888.
• [28] Immunohistochemical localization of keratins and involucrin in solar keratosis and Bowen's disease.Am J Dermatopathol. 1995 Apr;17(2):151-7. doi: 10.1097/00000372-199504000-00007.
• [29] Methyl aminolevulinate daylight photodynamic therapy applied at home for non-hyperkeratotic actinic keratosis of the face or scalp: an open, interventional study conducted in Germany.J Eur Acad Dermatol Venereol. 2019 Apr;33(4):661-666. doi: 10.1111/jdv.15422. Epub 2019 Feb 22.
• [30] Split-face study comparing conventional MAL photodynamic therapy in multiple actinic keratosis with complete time vs. half-time red light LED conventional illumination.J Eur Acad Dermatol Venereol. 2019 Aug;33(8):1529-1534. doi: 10.1111/jdv.15566. Epub 2019 Apr 15.