.In this section, we will first discuss the future treatments for precancer and then those for skin cancer.

Past treatments for precancers (actinic keratoses) had their limitations. In this section, we will look at interesting and exciting possible future treatments for precancers and cancers of the skin. See Treatment of Precancers to review the necessary background material for this discussion.

Photodynamic therapy (PDT) has been shown in tests to be very effective against precancers, unfortunately the manufacturer did not fully reveal the results of their initial studies showing not only significant pain during the treatment but also an increased time for treatment (ALA application). PDT for precancers, a chemical aminolevulinic acid (ALA) is applied topically (rubbed directly onto the skin). Only the abnormal (precancer) cells significantly change ALA into protoporphryn IX, a chemical that can be activated or energized by light. When a special visible light or laser of the right wavelength (type/color) is shone on the precancers containing protoporphryn IX, the loaded precancer cells are destroyed and the skin heals within a week. Claimed advantages of the ALA treatment over six weeks of fluorouracil are less chance of scarring and healing in only one week, with the disadvantage of a slight stinging only at the time of shining the treatment light. Disadvantages are that the PDT treatment is less effective for thick lesions that can be treated later with spot liquid nitrogen or biopsied by your doctor for testing. Precancers are usually thinner and respond the best to PDT, while skin cancers are usually thicker, respond less well and may merit a small biopsy.

A company DUSA has patents on the use of ALA and there have been few competitors within the first years of use. Reports from Doctors treating patients in the fourth quarter of 2000 revealed that the DUSA method needs to be applied for 16 minutes during which patients are in significant pain. This has been a deterrent for doctors regarding the purchase of DUSA machinery. DUSA management is hurriedly working on ways to minimize the intense skin pain during the treatment sessions. It will be tough for PDT to beat old-fashioned liquid Nitrogen which can be used to treat 100's of precancers in a fraction the time of PDT with much less pain and/or disfigurement.

Tazarotene sold under the brand name Tazorac is a vitamin A-like compound with some similarity to Retin-A. Tazarotene was first used by the website author to treat widespread keratoacanthoma and squamous cell carcinoma successfully prior to a specific FDA allowance for this indication (any patients using such a treatment prior to FDA approval receive extensive discussion and sign their acknowledgment of the "off (FDA) label usage". Although the treatment appears to work "to the naked eye of the examining doctor" the only way to be sure that the cancer is out is of course to perform extensive biopsies or a full Mohs surgery of the wound. Few doctors/professors of dermatology in private practice or even university based/academic practice or their patients would want extensive biopsies or extensive Mohs when their cancer(s) "look" like they are "cleared." So it is impossible to tell from a few reports, even by the website author, that Tazarotene "works" for skin cancer, especially squamous and possibly basal cell carcinoma. The website author feels that an area should remain "clear" to the doctor's naked eye for at least 5 years to declare a "cure" and that studies in younger persons below 50 years of age should be followed for 10 and 15 years to determine 10 and 15 year cure rates. The website author believes that 5 year cure rates should be viewed with suspicion when a treatment either surgical or medicinal or combination therapy is hailed. (Since the writing of this section, many articles in the medical/surgical literature have indicated that tazarotene has a beneficial effect in fighting squamous and basal skin cancers.) The website author has also used tazarotene for treatment of precancers that are resistant to other treatments and is reluctant to use tazarotene for actinic keratoses for the following reasons: expensive and not for use in women of childbearing age. The website author has a US patent on the usage of tazarotene to treat verruca (warts).

Diclofenac sodium sold under the brand name Solareze gel for the treatment of precancers = actinic keratoses. The drug has a modest effect in the hands of the website author for precancers and unfortunately needs to be used for 60 to 90 days and applied twice daily. Considering the expense and irritation to the skin in the areas of treatment for such a long time compared to all other treatments, the author has not found this drug to be a first line drug in the treatment of precancers. However, the website author would use diclofenac in a novel way that does not risk the DNA altering effects of 5-FU or Effudex or Fluoroplex. The new way would be to apply diclofenac to patients of possible suspected precancers would be the following. Apply diclofenac for 7 days twice daily, wait until the precancers are highlighted by the treatment and then treat with liquid nitrogen the "previously hidden (to the naked eye)" precancers. A nurse then could reliably apply the liquid nitrogen knowing that the lesions being treated have a high likelihood of being precancers.

Imiquimod 5%, sold under the brand name Aldara, is a immune system "modulator" which has effects of T-lymphocyte white blood cells. The drug was originally sold and marketed and FDA approved to treat warts of the genitals (penis, scrotum, vulva and peri-vaginal areas). This drug was used early-on by the website (with patients "off label" consent) by the website author to treat widespread porokeratoses, actinic keratoses, squamous cell cancer and basal cell cancer. Again, although the treatment appears to work "to the naked eye of the examining doctor" the only way to be sure that the cancer is out is of course to perform extensive biopsies or a full Mohs surgery of the wound. Few doctors/professors of dermatology in private practice or even university based/academic practice or their patients would want extensive biopsies or extensive Mohs when their cancer(s) "look" like they are "cleared." So it is impossible to tell from a few reports, even by the website author, that imiquimod "works" for skin cancer, especially squamous and possibly basal cell carcinoma. As stated under tazarotene, the website author feels that an area should remain "clear" to the doctor's naked eye for at least 5 years to declare a "cure" and that studies in younger persons below 50 years of age should be followed for 10 and 15 years to determine 10 and 15 year cure rates. The website author believes that 5 year cure rates should be viewed with suspicion when a treatment either surgical or medicinal or combination therapy is hailed. (Since the writing of this section, many articles in the medical/surgical literature have indicated that imiquimod has a beneficial effect in fighting squamous and basal skin cancers.) The website author has also used imiquimod as a second or third-line treatment of precancers that are resistant to other treatments and not as a first line therapy because it is extremely expensive and 3M (manufacturer) knows how to put the drug into tiny non-reusable packets. For larger skin cancers, or deeper ones, imiquimod currently does not penetrate well and causes some "nasty" irritating reactions during the long treatment time and thus may be expected to have a cure rate only of about 80% for some basal and squamous cell cancers. This is not a great cure rate and thus if the website author gives imiquimod to a 30 year old model with a basal cell cancer of the nose it is with the caution that 6 month follow-ups for the next 10 years are likely needed and that imiquimod treatment will possibly fail in 1 in 5 patients and that the model is taking a "gamble" and could later lose her nose to this "gamble."

3M, the manufacturer of Imiquimod 5%, allegedly has solved some of the penetration problem of imiquimod with a new topical relative of imiquimod that has 100 times the penetration. This may increase the cure rate to over 95%. The operative word is may and everything that was said about 5 year cure rates applies. Just because a few prominent or even non-prominent doctors eyeball a treated skin cancer 3 or 6 months following any of the aforementioned treatments does not mean that the skin cancer has been "cured" for the long term. If biopsies are not taken 5 years following "treatment" of a cancer in the exact measured and photographed area of treatment of a skin cancer with these treatments, then the website author is not convinced. Too many studies in medicine are published that a high school science student could properly criticize; the reason the studies get published, money and politics (which are usually synonymous). Even the prestigious New England Journal of Medicine now prostitutes itself by allowing their publishing doctors and scientists to openly be influenced by big drug company money. This is most unfortunate for the public indeed, especially in light of the occasional surfacing of some famous doctors and medical institutions "doctoring" their results to reach the conclusions they want (or are paid to find)..

For the treatment of melanoma, anti-angiogenesis drugs may see some use. Genentech has recently announced excellent results of their anti-angiogenesis product against bowel cancer. Dr. Robert Langer of MIT has developed one of the most promising of these drugs, derived from cartilage. Langer reasoned that since human cartilage contains few blood vessels, it should contain a chemical that prevents blood-vessel growth. Solid tumors and cancers need blood from blood vessels to grow. Langer found a chemical called troponin, produced by cartilage, that inhibits blood vessel growth. Troponin is the major component of the smooth-muscle cells that make up blood vessels themselves. The system is beautifully simple because the presence of too much troponin, which makes up blood vessels, cuts down on the production of more blood vessels. One beautiful thing about troponin is that it is a very small protein molecule and is therefore easy to synthesize. It is a classic case of feedback inhibition, which is exactly the method the body's parts use to keep in balance.

Dr. Langer was trained by Dr. Folkman, whose angiostatin and endostatin are owned by the Entremed Company. Dr. Folkman's lab is above Dr. Langer's lab in Boston. The mouse studies that showed Entremed's product "worked 60% effectively" showed that troponin, held by Boston Life Sciences, Inc. (BLSI), was over 90% effective against the same melanoma mouse model. Troponin can be made recombinantly, with the genes of microorganisms, without the use of human blood and will be ready for human testing in early 1999. Entremed's product, angiostatin, is a large, complicated molecule difficult to synthesize without using human blood, which has drawbacks like AIDS, hepatitis and other diseases. As of July 1998, Entremed had not yet successfully recombinantly synthesized (made) angiostatin. Entremed and BLSI both have many hurdles to overcome just to continue to survive.

BLSI's strong suit appears to be scientists and not management. BLSI has access to some of the best scientists in the world, mostly all Harvard and MIT doctors and scientists. Previous BLSI Board Members have showered themselves with numerous options and benefits that may saddle the company financially. Another question is whether BLSI management will blunder somehow and miss yet another deadline for human testing in the clinic. Again, BLSI's scientists are among the best in the world and have numerous other patents for nerve and spinal cord regenerating compounds, Parkinson's disease, restenosis inhibitors for the heart, immune system modulators and more. The question for BLSI investors is the universal "small biotech" question. Will the company run out of money before any of their drugs "hit" and what will be left for the common shareholders?

In conclusion, melanoma and possibly squamous-cell carcinoma may see treatment with anti-angiogenesis drugs in conjunction WITH other therapy, including chemotherapy. As more promising drugs or treatments become newsworthy, they will be added to this section.