Table 1 The approved and currently under trials treatment modalities for the cSCC. The Table was modified from Mårten et al. (https://0-www-nature-com.brum.beds.ac.uk/articles/s41568-023-00583-5) 

Conventional Treatment/Therapies

 Excision

Surgical removal of cancer cells

Localised cSCC

Yes

[122]

 Mohs

Progressive resection of tissues layers containing cancer cells by minimizing the removal of healthy tissues

Localised cSCC

Yes

 Cryotherapy

Freezing and destroying the tumor by applying liquid nitrogen

Superficial; Localised cSCC

Yes

 Photodynamic

The initiation of tumor-ablation reaction by applying light source with therapeutics

Localised cSCC

Yes

 Radiation

High-energy radiations

Locally advanced, recurrent, or metastatic cSCC

Yes

 Topical with therapeutics

Application of chemotherapeutics (5-flurouracil or imiquimod)

Superficial; Localised cSCC

Yes

 Systemic chemotherapy

Single or combination therapies of different chemotherapeutics such as cisplatin and 5-flurouracil

Locally advanced, recurrent, or metastatic cSCC

Yes

Systemic Targeted Therapy

 Gefitinib

EGFR tyrosine kinase inhibitor

Locally advanced, recurrent, or metastatic cSCC

No

[123]

 Lapatinib

EGFR tyrosine kinase inhibitor

Locally advanced, recurrent, or metastatic cSCC

No

[124]

 Erlotinib

EGFR tyrosine kinase inhibitor

Locally advanced, recurrent, or metastatic cSCC

Yes, for NSCLC

[125]

 Panitumumab

Monoclonal antibody that targets the extracellular domain of EGFR and inhibits it

Locally advanced, recurrent, or metastatic cSCC

No

[126]

 Cetuximab

Monoclonal antibody that competitively inhibits the EGFR

Locally advanced, recurrent, or metastatic cSCC

Yes, for HNSCC

[125]

Systemic Immunotherapy

 Cemiplimab

PD1 checkpoint inhibitor

Locally advanced,recurrent, or Metastatic cSCC, not curable with surgery or radiation therapy

Yes

[127]

 Nivolumab

PD1 checkpoint inhibitor

Locally advanced, recurrent, or Metastatic cSCC, not curable with surgery or radiation therapy

Yes

[125]

 Pembrolizumab

PD1 checkpoint inhibitor

Locally advanced, recurrent, or Metastatic cSCC, not curable with surgery or radiation therapy

Yes

[128]

 Ipilimumab

CTLA-4 checkpoint inhibitor

Locally advanced, recurrent, or Metastatic cSCC, not curable with surgery or radiation therapy

yes

[125]

Combination therapies

 Cetuximab + 5FU + Cisplatin

EGFR inhibitor + Chemotherapeutic agents (Cetuximab + 5FU + Cisplatin)

Or

5FU + Cisplatin

Platinum-resistant metastatic SCC

Yes, for HNSCC

[129]

 Pembrolizumab + chemotherapy

PD1 checkpoint inhibitor + Chemotherapeutic agents

Metastatic or locally advanced cSCC,

Yes, for HNSCC

[130]

Intralesional therapy

 5 Fluorouracil

Anti-cancer/cytotoxic effects

Localised, early stage cSCC

No

[131]

 Methotrexate

Anti-cancer/cytotoxic effects

Localised, early stage cSCC

No

[132]