Managing skin cancer: New treatment modalities may soon be available for clinical use

October 1, 2008

Gene, molecular and cell-targeted therapies are under investigation for the treatment and prevention of nonmelanoma skin cancers, and some of these modalities may be available for clinical use soon. Recent and forthcoming advances in imaging are also enhancing tumor visualization and surgical planning.

Key Points

Chicago - New methods for treating and preventing nonmelanoma skin cancer may be on the horizon, but surgery will continue to play a primary role in the management of basal cell and squamous cell carcinoma, said Allison T. Vidimos, M.D., at the Summer American Academy of Dermatology Meeting 2008.

"New modalities currently under investigation will likely be used as adjuncts to surgery or perhaps as alternatives in patients who are not good surgical candidates," says Dr. Vidimos, chairman, department of dermatology, Cleveland Clinic, Cleveland, Oh.

Dr. Vidimos provided an overview of some recently available and forthcoming developments in skin cancer diagnosis, treatment and prevention.

GDC-0449 is an oral compound that was investigated in a phase 1 clinical trial of 36 patients with a variety of end-stage cancers. The population included nine patients with metastatic basal cell carcinoma (BCC), and promising responses were achieved in this early-stage clinical trial.

Plant extract

Cyclopamine is a naturally occurring plant extract that is being developed for topical application.

In preclinical studies, it was found to inhibit BCC growth in mice, and it has also been shown to shrink BCCs in patients with basal cell nevus syndrome and sporadic BCCs, Dr. Vidimos tells Dermatology Times.

Nanotechnology

The potential of nanotechnology to advance diagnosis and treatment of skin cancer is also being explored. Possible applications include the delivery of PDT and chemotherapy agents into tumor cells.

In addition, noble metal nanoparticles having strong surface electric fields that absorb and scatter electromagnetic radiation offer the potential for simultaneous cancer cell imaging and photothermal therapy.

For example, when gold nanorods conjugated to anti-EGF monoclonal antibodies were incubated with a nonmalignant epithelial cell line and two malignant oral epithelial cell lines, they were found to bind specifically and with higher affinity to the malignant cells that overexpress the EGF receptor on their cytoplasmic membrane.

DNA

Research has also been ongoing evaluating the bacterial DNA repair enzyme T4 endonuclease 5 as a topical chemopreventive agent. This strategy has yielded encouraging results when tested for reducing the development of actinic keratoses and nonmelanoma skin cancers in normal individuals and patients with xeroderma pigmentosa, and it now has fast-track designation from the Food and Drug Administration (FDA).

RNA interference

RNA interference is a post-transcriptional mechanism of gene silencing that involves inhibition of protein translation or direct degradation of messenger RNA (mRNA).

In preclinical studies performed so far in cell culture systems and animal models, RNA interference has been used successfully to silence critical gene products involved in carcinogenesis.

"The challenges with RNA interference involve successful in vivo delivery, complete suppression of the targeted gene, and avoidance of nonspecific immune effects. However, initial clinical studies are on the horizon," Dr. Vidimos says.

Important radiology advances are already in the hands of clinicians, with CT and MRI now being commonplace tools in patient evaluation and management.

PET CT scanning is being used for staging, and with higher field strength units, MRI now offers improved spatial resolution so that lesion detail on MRI images almost parallels that seen on histological evaluation.

Multidetector CT scanners able to create a 3D picture by fusing axial, coronal and sagittal images are being used to visualize tumor bulk and its relationship to adjacent structures.

"These diagnostic tools are valuable for surgical planning and for helping the dermatologic surgeon identify when to engage a multidisciplinary team of surgeons.

"In addition, the information they provide can help in counseling efforts to prepare patients for extensive surgery, a complex repair and expected postoperative morbidity," Dr. Vidimos says.