Disease Briefing

Cutaneous squamous cell carcinoma: research and therapeutic landscape

A live synthesis of what is being targeted, what is being trialled, which datasets exist, and where the actionable gaps sit — assembled from public APIs, with every figure traceable to its source.

Generated 2026-09-17Sources Open Targets · ClinicalTrials.gov · openFDA · GEO · PubMed · Europe PMC · iCite · RePORTERRanked 96 studies · 2,360 GEO samples
Reading as
Reorders emphasis only — nothing is hidden or loaded on demand.

Answer block

12 genes recurrently implicated in cutaneous squamous cell carcinoma — TP53, CDKN2A, NOTCH1, NOTCH2, EGFR, HRAS, KMT2D, FAT1, PDCD1, CD274, TGFBR1, CASP8 — triaged for what can actually be aimed at them, alongside the trials, public datasets, literature and funding around the disease. Every figure below carries its source and retrieval date in the section it comes from.

3
drugs carry an FDA label naming cutaneous squamous cell carcinoma: Cemiplimab, Cosibelimab, Pembrolizumab. This counts labels, not treatment — the disease is also treated with agents approved under broader indications
2
of the 12 genes above carry a drug that is approved in cutaneous squamous cell carcinoma itself — CD274, PDCD1. Across all of them 137 drug entries reach these genes, 128 distinct once salt forms are merged
0
registered PD-1 cell-therapy trials in cutaneous squamous cell carcinoma, 0 active. Counted from ClinicalTrials.gov across 7 synonyms, deduplicated by NCT id, interventional studies only — the query is published in the JSON beside this page so the number can be re-derived
8
targets carry an Open Targets tractability signal and have no clinical programme of any kind: TP53, NOTCH1, NOTCH2, HRAS, KMT2D, FAT1, TGFBR1, CASP8
170
human GEO series match the disease; 96 survive on-topic filtering, and only 1 are patient cohorts of 100+ samples
29
Europe PMC full-text papers name GSE45216 — the highest accession-mention count in the set. A mention is not proof of reanalysis, so read it as reach rather than reuse
$8.3M
NIH obligations in FY2025, up 132% since 2013 — while distinct core projects went 15 to 20. Larger awards rather than more distinct core projects; core projects are not the same unit as laboratories

Target landscape

Open Targets · retrieved 2026-09-17 · weekly

12 genes recurrently implicated in cutaneous squamous cell carcinoma, triaged for whether anything can actually be aimed at them. The zeros are the informative rows.

Of 12 recurrently implicated genes, 9 carry any drug at all. That is a statement about these 12 gene targets, not about the disease: Cutaneous squamous cell carcinoma does have labelled therapy — 3 drugs, listed in the next section.

Two different questions

The table below asks what can be aimed at 12 recurrently implicated genes. That is narrower than what is approved for the disease, and narrower again than what cutaneous squamous cell carcinoma is actually treated with, which includes agents approved under broader indications. All three are on this page and they are kept apart deliberately.

GeneDrugsApproval, and whether it reached this diseaseOpen Targets tractabilitycomputed from protein features and literature — a signal that a modality is worth trying, not evidence that it worksCell therapy here
TP53 across cancers → 8 Phase 3Alrizomadlin, Cenersen, Contusugene Ladenovec, Eprenetapopt, Idasanutlin, Navtemadlin, Siremadlin, TeprasiranNo cutaneous squamous cell carcinoma trial of any of these drugs other clinical modality, protein degrader, small molecule
CDKN2A across cancers → 0 No drug
NOTCH1 across cancers → 1 Phase 1BrontictuzumabNo cutaneous squamous cell carcinoma trial of any of these drugs antibody, protein degrader, small molecule
NOTCH2 across cancers → 1 Phase 2TarextumabNo cutaneous squamous cell carcinoma trial of any of these drugs antibody, protein degrader, small molecule
EGFR across cancers → 74 23 approvedAfatinib, Afatinib Dimaleate, Amivantamab, Aumolertinib, Brigatinib, Cetuximab, Cetuximab Sarotalocan, Dacomitinib, Erlotinib, Gefitinib, Icotinib, Lapatinib, Lapatinib Ditosylate, Lazertinib, Mobocertinib, Necitumumab, Neratinib, Nimotuzumab, Olmutinib, Osimertinib, Panitumumab, Rociletinib, VandetanibApproved in non-small cell lung carcinoma, anaplastic large cell lymphoma, malignant tumor of neck and 14 other indications. No cutaneous squamous cell carcinoma indication appears on these drugs’ labels.9 active of 32 cutaneous squamous cell carcinoma trials antibody, other clinical modality, protein degrader, small molecule
HRAS across cancers → 1 Phase 2SalirasibNo cutaneous squamous cell carcinoma trial of any of these drugs antibody, protein degrader, small molecule
KMT2D across cancers → 0 No drug antibody, protein degrader, small molecule
FAT1 across cancers → 0 No drug antibody, protein degrader
PDCD1 across cancers → 26 9 approvedCemiplimab, Dostarlimab, Nivolumab, Pembrolizumab, Retifanlimab, Serplulimab, Sintilimab, Tislelizumab, ToripalimabApproved in cutaneous squamous cell carcinoma: Cemiplimab, Pembrolizumab.53 active of 95 cutaneous squamous cell carcinoma trials antibody, other clinical modality, protein degrader, small molecule
CD274 across cancers → 13 5 approvedAtezolizumab, Avelumab, Cosibelimab, Durvalumab, SugemalimabApproved in cutaneous squamous cell carcinoma: Cosibelimab.8 active of 17 cutaneous squamous cell carcinoma trials antibody, other clinical modality, protein degrader, small molecule
TGFBR1 2 Phase 2/3Galunisertib, VactosertibNo cutaneous squamous cell carcinoma trial of any of these drugs antibody, protein degrader, small molecule
CASP8 2 Phase 2Emricasan, NivocasanNo cutaneous squamous cell carcinoma trial of any of these drugs antibody, protein degrader, small molecule

Dataset evidence counts studies in the 96-study ranked set whose title or abstract names the gene; the bar is scaled to EGFR. Sources: Open Targets Platform and NCBI GEO, retrieved 2026-09-17. Clinical stage is the highest reached for any indication — see the per-drug indications noted in each row. Target-prioritisation reference only; not clinical or prescribing guidance.

What is actually approved here

openFDA drug labels · weekly

3 drugs carry an FDA label naming cutaneous squamous cell carcinoma: Cemiplimab, Cosibelimab, Pembrolizumab. Separately, 34 of the drugs returned for the genes in the table above are approved only for other diseases and reach cutaneous squamous cell carcinoma through trials, not through their labels.

3Labelled for cutaneous squamous cell carcinomaFDA INDICATIONS AND USAGE names the disease
34Approved, but for another diseasereturned for the genes in the table above
0Backbone agents listing itbroad cytotoxics whose labels name many tumours

Every label that names cutaneous squamous cell carcinoma

DrugRoleWhat the label says
CemiplimabLIBTAYOLabelled hereCutaneous Squamous Cell Carcinoma LIBTAYO is indicated for the treatment of adult patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.
CosibelimabUNLOXCYTLabelled hereUNLOXCYT is indicated for the treatment of adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.
PembrolizumabKEYTRUDA, KEYTRUDA QLEXLabelled hereCutaneous Squamous Cell Carcinoma (cSCC) for the treatment of patients with recurrent or metastatic cSCC or locally advanced cSCC that is not curable by surgery or radiation.

0 labels match indications_and_usage:"cutaneous squamous cell carcinoma" OR indications_and_usage:"squamous cell carcinoma of the skin" OR indications_and_usage:"cutaneous squamous cell cancer"; they collapse to 3 distinct molecules once salt forms, biosimilars and co-formulated hyaluronidase are merged. Source: openFDA drug label API (api.fda.gov/drug/label.json), retrieved 2026-09-17. Labels change; this reflects the current label text, not the approval history. Not prescribing guidance.

Cell therapy

ClinicalTrials.gov · retrieved 2026-09-17 · weekly

No cell-therapy trial in this disease names one of the antigens in the profile. That is a finding, not a gap in the query: the antigens searched are listed in the machine-readable facts alongside the synonyms used.

Research momentum

PubMed MeSH · monthly

Every term below is a share of the cutaneous squamous cell carcinoma literature, not a count, because the field itself grew: 2015–2018 (n=1,111) against 2021–2025 (n=1,429). A topic whose papers doubled while the field doubled has not risen.

Rising, with a real baseline

MeSH term2015–182021–25ChangeShare now
Antibodies, Monoclonal, Humanized0.9%7.63%8.47×109 papers
Antineoplastic Agents, Immunological0.9%3.57%3.96×51 papers
RNA, Long Noncoding0.54%1.61%2.98×23 papers
Tumor Microenvironment1.17%2.94%2.51×42 papers
Epidermolysis Bullosa Dystrophica0.99%2.17%2.19×31 papers
Transcriptome0.81%1.68%2.07×24 papers
Sweat Gland Neoplasms0.54%1.12%2.07×16 papers
Quality of Life0.72%1.4%1.94×20 papers
Epithelial Cells0.54%0.91%1.68×13 papers
Programmed Cell Death 1 Receptor1.26%2.1%1.67×30 papers

Cooling

MeSH term2015–182021–25ChangeShare now
Biopsy7.83%2.1%0.27×30 papers
Time Factors3.42%0.91%0.27×13 papers
Epidermis3.15%0.91%0.29×13 papers
Survival Rate2.7%0.84%0.31×12 papers
Cell Transformation, Neoplastic3.87%1.19%0.31×17 papers
Follow-Up Studies5.22%1.68%0.32×24 papers

Biggest topics now

MeSH term2015–182021–25ChangeShare now
Skin Neoplasms99.28%98.81%1.0×1412 papers
Neoplasm Recurrence, Local6.03%9.24%1.53×132 papers
Prognosis8.46%8.96%1.06×128 papers
Neoplasm Staging8.01%8.12%1.01×116 papers
Cell Proliferation8.19%7.77%0.95×111 papers
Antibodies, Monoclonal, Humanized0.9%7.63%8.47×109 papers
Gene Expression Regulation, Neoplastic7.56%6.72%0.89×96 papers
Treatment Outcome10.08%6.51%0.65×93 papers
Keratosis, Actinic8.19%5.88%0.72×84 papers
Skin8.73%5.88%0.67×84 papers

Publication mix

Type2015–182021–25
Randomized Controlled Trial0.8%0.5%
Review8.5%9.3%
Meta-Analysis0.5%0.9%
Case Reports0.0%3.8%

Query: ("Carcinoma, Squamous Cell"[Majr] AND "Skin Neoplasms"[Majr]) NOT ("Squamous Cell Carcinoma of Head and Neck"[MeSH] OR "Mouth Neoplasms"[MeSH] OR "Esophageal Squamous Cell Carcinoma"[MeSH] OR "Uterine Cervical Neoplasms"[MeSH] OR "Lung Neoplasms"[MeSH] OR "Melanoma"[MeSH] OR "Basal Cell Carcinoma"[MeSH]). Terms need at least 12 papers in the recent window and, in the rising table, at least 5 in the earlier one — a term going from 1 paper to 12 is a large fold change and no evidence of anything. Ubiquitous descriptors (Humans, Animals, age bands) and the disease’s own term are dropped. Source: PubMed MeSH, retrieved 2026-09-17.

Disease burden

What the public sources count, and how closely each category matches this disease. The same figures for every disease on the site are on one table.

MeasureValueMatchWhat it counts
New cases each year5,400,000 cancers/year (lesions, not people)proxycounts basal and squamous cell skin cancer (lesions, not people), which is broader than this disease
New cases each year, estimated1,080,000 cancers/year (lesions, not people)derived proxy5,400,000 x 0.2, from basal and squamous cell skin cancer (lesions, not people)
Deaths each yearnot publishedNot published: the page says deaths are not tracked by registries. Older estimates put cutaneous squamous cell deaths in the low thousands a year; none is a figure this profile can quote from a page.
Five-year relative survivalnot publishedNot published; the disease is not registered, so no relative survival exists. The page says most are cured by local treatment.
Median age at diagnosisnot publishedNot published; the page says risk "goes up as people get older".

Years of life lost: not computed. Years of life lost needs survival, age at diagnosis and a case count. five_year_relative_survival, median_age_at_diagnosis is not recorded for this disease.

Funding

NIH RePORTER · quarterly

NIH obligations naming cutaneous squamous cell carcinoma, after removing the 746 records across all years that matched the search but are about something else. That filter is not cosmetic: without it this section reports another field’s funding as this disease’s.

$8.3MNIH obligations, FY2025from $3.6M in FY2013 · +132%
20distinct projects funded15 in FY2013
$9.1Mpeak year was FY2023obligations, all institutes
71%of FY2025 awards from NCI15 of 21

NIH obligations by fiscal year

$2M$5M$7M$9M13151719212325
YearObligationsAwardsDistinct projectsDropped as off-topic
FY2013$3.6M161557
FY2014$2.5M101063
FY2015$3.4M131260
FY2016$4.4M141249
FY2017$4.3M9951
FY2018$2.6M9963
FY2019$4.3M121163
FY2020$4.5M151355
FY2021$6.5M211965
FY2022$8.5M252169
FY2023$9.1M252352
FY2024$8.0M252345
FY2025$8.3M212054

Where FY2025 money went

InstitutionObligationsAwards
Phusis Therapeutics, Inc.$2.1M1
University Of California, San Francisco$1.1M2
University Of Louisville$0.8M2
Division Of Basic Sciences - Nci$0.8M1
Stanford University$0.7M0
H. Lee Moffitt Cancer Ctr & Res Inst$0.6M1
Massachusetts General Hospital$0.5M0
University Of Virginia$0.5M1
University Of Texas At Austin$0.4M1
Ohio State University$0.4M1

Text search cutaneous squamous cell carcinoma OR skin squamous cell carcinoma over project title, terms and abstract, per fiscal year. Awards are individual funding actions; distinct projects collapse them by core project number, so a multi-year grant counts once. The most recent year may be incomplete. Source: NIH RePORTER, retrieved 2026-09-17.

Who funds it, FY2025

The total says how much. These say who from, through what kind of award, and to whom — which a dollar figure cannot.

NIH institutes

NCI15 · 71%
VA3 · 14%
NIEHS2 · 10%
NIAMS1 · 5%

Projects by administering institute. The rows above are the top 4 and account for 21 of 21.

Award mechanisms

R0110 · 48%
I013 · 14%
F302 · 10%
R441 · 5%
K081 · 5%
ZIA1 · 5%

R01 is an investigator-initiated grant; ZIA is NIH intramural, meaning the work happens inside NIH rather than being funded outside it. The rows above are the top 9 and account for 21 of 21.

Where it lands

Phusis Therapeutics, Inc.$2.1M · 25.1%
University Of California, San Francisco$1.1M · 13.1%
University Of Louisville$0.8M · 9.7%
Division Of Basic Sciences - Nci$0.8M · 9.6%
Stanford University$0.7M · 7.9%
H. Lee Moffitt Cancer Ctr & Res Inst$0.6M · 7.7%

Share of $8.3M in FY2025. The top three hold 48%.

Public datasets, ranked

NCBI GEO + Europe PMC + iCite · weekly

170 human GEO series match cutaneous squamous cell carcinoma. Keyword relevance cannot tell a 105-sample patient cohort from a six-well cell-line experiment, so this ranking scores four things GEO does not expose: how often the accession is named in full-text papers, field-normalised citation impact, clinical annotation, and cohort type.

Composition of the 96-study ranked set

unspecified 38patient 23cell line 20mixed 11xenograft 4
38 unspecified23 patient20 cell line11 mixed4 xenograft29 carry clinical annotation12 carry survival1 patient cohorts ≥100 GEO samples2,360 GEO samples totalin 5 single-cell series a GEO sample is one cell, not one patient

Established

high reuse, older
AccessionStudySamplesMentionsEurope PMCRCREvidence
GSE45216Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling2014 · array40292.4
APT 0.7579 cites
GSE139505Comprehensive analysis of transcriptomic changes in cutaneous squamous cell carcinoma2020 · sequencing1693.1
patient cohortAPT 0.7569 cites
GSE42677Defining an invasion signature at the leading edge of cutaneous squamous cell carcinoma (SCC): IL-24 driven MMP-7 and MMP-13 expression.2013 · array25281.7
cell lineAPT 0.558 cites
GSE74758circRNA expression in cutaneous squamous cell carcinoma (cSCC)2016 · array674.1
patient cohortAPT 0.75114 cites
GSE32979Cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients2013 · array94172.6
APT 0.7585 cites
GSE145328Decreased cytotoxic T cells and TCR clonality in organ transplant recipients with squamous cell carcinoma2020 · single-cell1141.2
patient cohortAPT 0.25molecularTIL29 cites
GSE45164Transcription profiling of human skin squamous cell carcinoma (SCC)2014 · array13251.5
APT 0.2557 cites
GSE159093Improving the efficacy of EGFR inhibitors by topical treatment of cutaneous squamous cell carcinoma with miR-634 ointment2020 · array821.0
mixedAPT 0.5survivalmolecularEGFRGEFITINIB20 cites

Recent

2022 onward, by score
AccessionStudySamplesMentionsEurope PMCRCREvidence
GSE289743Cancer-induced nerve injury promotes resistance to anti-PD-1 therapy [RNA-Seq FFPE]2025 · sequencing83218.4
APT 0.75survivalmolecularPD-172 cites
GSE193304Single-cell Sequencing Highlights Heterogeneity and Malignant Progression in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma2023 · chromatin1493.5
patient cohortAPT 0.547 cites
GSE284467Multi-omic Sequencing of Intermediate to High-Risk Cutaneous Squamous Cell Carcinoma Identifies Critical Genes and Expression Patterns Associated with Disease and Poor Outcomes2024 · sequencing752
survivalstagemolecularCDKN2ANOTCH1TP53
GSE178845CD271 activation prevents low to high-risk progression of cutaneous squamous cell carcinoma and improves therapy outcomes2023 · sequencing610.8
mixedAPT 0.25survivalstagemolecular8 cites
GSE175463TINCR lncRNA encodes a ubiquitin-like protein that activates CDC42, promotes epithelial differentiation and suppresses tumor growth2022 · sequencing5812.7
cell lineAPT 0.25survival43 cites
GSE191334Bulk RNA-Seq of cutaneous squamous cell carcinomas (cSCC) with paired normal controls2022 · sequencing1680.8
APT 0.2511 cites

Sources: NCBI GEO + Europe PMC + iCite, retrieved 2026-09-17. SubSeries are collapsed to one row per study by linked PMID. Of 170 series retrieved, 12 were dropped by the profile’s exclusion rules and 40 named the disease only in passing. The ranked set is a relevance-ranked sample, not a census, so the composition figures describe the sample only.

Where the gaps are

Derived from the sections above · recomputed on every refresh

Each card below is a disagreement between two of the tables on this page — a drug that exists but was never tried here, a target that looks tested and was not, a gene with no drug whose product has a busy clinical programme. They are computed from the same facts as the tables, so they cannot contradict them.

CDKN2A

No drug, no trial, no clinical programme of any kind. Whatever the biology says, nothing has been built.

KMT2D

No drug, no trial, no clinical programme of any kind. Whatever the biology says, nothing has been built.

FAT1

No drug, no trial, no clinical programme of any kind. Whatever the biology says, nothing has been built.

How a machine reads this page

Static

This page is written to be quoted correctly by a model as much as read by a person. The same facts are available as JSON at the sibling URL below, which is what to cite. The cross-disease layer — burden, genes, drugs and antigens across every briefing — is described at /disease/api.json.

Fully server-rendered

Every figure is in the HTML at first byte. No JavaScript runs, no figure is fetched after load, and nothing on this page requires a renderer to see.

Every number carries a source

Each section names the API it came from and the date it was retrieved: Open Targets (2026-09-17), ClinicalTrials.gov (2026-09-17), openFDA (2026-09-17), NCBI GEO (2026-09-17), PubMed (2026-09-17), NIH RePORTER (2026-09-17).

Negatives stated explicitly

Where nothing exists for cutaneous squamous cell carcinoma — no drug, no trial, no approval — the page says so in those words rather than omitting the row. An absent row is unquotable; a stated negative is the finding.

Denominators, not just percentages

Every share is printed with the count and the total it came from, so a figure can be checked rather than taken.

The filters are published

5 exclusion patterns are applied to free text before anything is ranked, because A431 (an EGFR workhorse) is used as a model system in EGFR signalling and trafficking, receptor biology, drug delivery. What was removed and why is stated in each section rather than silently applied.

{
  "disease": "Cutaneous squamous cell carcinoma",
  "mesh": "Carcinoma, Squamous Cell",
  "facts": "https://usebiotransfer.org/disease/cutaneous-squamous-cell-carcinoma.json",
  "methods": "https://usebiotransfer.org/methods/",
  "all_diseases": "https://usebiotransfer.org/disease/api.json",
  "note": "Every figure on the page is in that JSON with its source and retrieval date. Quote from it rather than from the HTML."
}