Oncology Intelligence

Skin Cancer
2:40 AM|Bruce V. Bigelow|MIT Biotech Group - Essential Biotech RSS Feed|Labels: skin cancer, clinical trial
Ignyta CEO Jonathan Lim (Xconomy image by BVBigelow 2016)

Biotech CEO Jonathan Lim co-founded Ignyta in 2011 to commercialize a new approach to diagnosing and treating rheumatoid arthritis, based on discoveries that showed how changes in methyl group molecules associated with the human genome could change the way genes function.

Instead, Lim may end up showing how to breathe new life into a life sciences company that was flat-lining, at least in terms of developing new technology.

As a tool for diagnosing rheumatoid arthritis and other autoimmune diseases, Ignyta’s technology failed in early 2013, Lim said in a recent interview.

Lim (pictured above) was lucky in some respects, though. He had closed on $6 million in financing just a few months earlier. Of the options he faced at the time—forge ahead with the diagnostic tool despite adverse test results, close down the company and return the capital to investors, or come up with an alternative—Lim decided to pivot, and switched Ignyta’s focus from autoimmune diseases to cancer.

Now Lim is awaiting interim results of a global pivotal clinical trial that could determine Ignyta’s ultimate fate. He said he anticipates the company (NASDAQ: RXDX) will disclose its interim findings sometime next spring.

If the results of what Lim calls Startrk-2 confirms the data from a prior clinical trial, in which 24 patients with different solid tumors showed a 79 percent response rate, Ignyta would likely seek FDA approval for entrectinib, its lead drug candidate.

The outcome of the prior clinical trial (Startrk-1) was exciting, Lim said, because patients in the study were diagnosed with seven different tumor types, including non-small cell lung cancer, head and neck cancer, renal cell carcinoma, and melanoma. Despite the variety of tumor types, Ignyta’s genomic analyses showed that all of the patients enrolled in the study had one of five specific gene fusions. Such fusions occur when a piece of one chromosome fuses with part of another chromosome to form an oncogene, an abnormal gene capable of causing cancer.

Fusion oncogenes frequently act alone in driving cancers, Lim said, and the five specific oncogenes are part of … Next Page »

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Monday, September 19, 2016 7:15 AM|Avi Bitterman|Journal of the American Academy of Dermatology|Labels: melanoma, skin cancer, biomarker diagnostic
The current gold standard in the diagnosis of melanoma is histopathologic examination under hematoxylin–eosin stain, with occasional immunohistologic adjunctive staining. Despite the expert evaluation of numerous dermatopathologists, the differentiation of melanoma from benign nevi can prove quite challenging in intermediate cases. In difficult melanocytic tumors, concordance among dermatopathologists can be as low as 54.5%.1 In response to the discordance among dermatopathologists, various molecular tests designed to differentiate benign nevi from melanoma have been developed with promising results.
Wednesday, September 14, 2016 4:23 PM|E. Bernhart, I. Plastira, N. Kogelnik, M. Göritzer, K. Fan, C. Wadsack, G. Rechberger, J. Becker, W. Sattler|JournalTOCs API - Journal of Investigative Dermatology (875 articles)|Labels: S1P, skin cancer

484 Merkel cell carcinoma proliferation is regulated by sphingosine-1-phosphate-mediated pathways in vitro
V. Bhat Kumble E. Bernhart, I. Plastira, N. Kogelnik, M. Göritzer, K. Fan, C. Wadsack, G. Rechberger, J. Becker, W. Sattler
Journal of Investigative Dermatology, Vol. 136, No. 9 (2016) pp. S243 -
Merkel cell carcinoma (MCC) is an aggressive metastatic neuroendocrine skin cancer associated with high recurrence and mortality rates. Sphingolipids (SL) represent a major class of bioactive lipids potently regulating cell proliferation, migration, and apoptosis. In particular pro-survival sphingosine 1-phosphate (S1P) plays a prominent role in tumor biology. De novo synthesis of S1P and its precursor ceramide begins from condensation of serine and palmitoyl-CoA catalysed by serine palmitoyltransferases (SPTLC) 1-3.

Wednesday, September 14, 2016 4:23 PM|C. Andres|JournalTOCs API - Journal of Investigative Dermatology (875 articles)|Labels: skin cancer

482 Toll-like receptor 7: A new marker for differentaiation of nonmelanoma skin cancer'
N. Ritter R. Franz, R. Hein, T. Biedermann, K. Eyerich, N. Garzorz-Stark, C. Andres
Journal of Investigative Dermatology, Vol. 136, No. 9 (2016) pp. S242 -
Toll-like receptors (TLR) recognizing damage/danger-associated molecular patterns (DAMPs) which are released from damaged cells but also from cells undergoing malignant transformation have been in the focus of tumor research. In particular TLR7 agonists have been established as effective agents to treat superficial cutaneous tumors such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In this context, a trend for higher tumor clearance rates upon imiquimod treatment for SCC as compared to BCC have been published suggesting different TLR7 expression on baseline level and/or during imiquimod treatment.

Wednesday, September 14, 2016 4:21 PM|Fred Hutchinson Cancer Research Center/UW Medicine Cancer Consortium - Clinical Trials|Labels: PD-1/PD-L1, skin cancer, clinical trial
This phase I/II trial studies the side effects and how well localized radiation therapy or recombinant interferon beta and avelumab with or without cellular adoptive immunotherapy works in treating patients with Merkel cell carcinoma that has spread to other parts of the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Interferon beta is a substance that can improve the body's natural response and may interfere with the growth of tumor cells. Monoclonal antibodies, such as avelumab, may help T lymphocytes kill tumor cells. For cellular adoptive immunotherapy, specific white blood cells are collected from the patient's blood and treated in the laboratory to recognize Merkel cell carcinoma. Infusing these cells back into the patient may help the body build an effective immune response to kill Merkel cell carcinoma. Giving localized radiation therapy or recombinant interferon beta and avelumab with or without cellular adoptive immunotherapy may be a better treatment for Merkel cell carcinoma.
Wednesday, September 14, 2016 4:21 PM|Fred Hutchinson Cancer Research Center/UW Medicine Cancer Consortium - Clinical Trials|Labels: PD-1/PD-L1, skin cancer, clinical trial
This phase II trial studies how well pembrolizumab works in treating patients with Merkel cell cancer that cannot be removed by surgery or controlled with treatment, or has spread to other parts of the body. Pembrolizumab may stimulate the immune system to identify and destroy cancer cells.
Wednesday, September 14, 2016 4:21 PM|Fred Hutchinson Cancer Research Center/UW Medicine Cancer Consortium - Clinical Trials|Labels: skin cancer
Phase II Study of Neukoplast (NK-92) Infusions in Patients with Unresectable Stage III (IIIB) or Distant Metastatic (IV) Merkel Cell Carcinoma (MCC).
Wednesday, September 14, 2016 4:21 PM|Fred Hutchinson Cancer Research Center/UW Medicine Cancer Consortium - Clinical Trials|Labels: cervical cancer, skin cancer, clinical trial
The purpose of this study to investigate the safety and efficacy of using nivolumab to treat subjects who have virus-associated tumors. Certain viruses that infect human cells have been known to play a role in tumor formation and growth. This study will investigate the effects of the study drug nivolumab in human subjects who have the following types of viral-associated tumors: Gastric Cancer, nasopharyngeal carcinoma , cervical cancer, vaginal cancer, vulvar cancer, squamous cell carcinoma of the head and neck, and Merkel Cell Carcinoma.
Wednesday, September 14, 2016 11:10 AM|Sini J Kalapurakal, James Malone, K. Thomas Robbins, Lucinda Buescher, John Godwin, Krishna Rao|Journal of Cancer|Labels: skin cancer

Objectives: Non-melanoma skin cancer is the most common malignancy in US, with an annual incidence of in excess of 1.5 million cases. In the majority of cases, locoregional treatment is curative and systemic therapy is not indicated. Platinum-based chemotherapy regimens have been used most commonly in refractory cases. The use of cetuximab, a monoclonal antibody targeting epidermal growth factor receptor [EGFR], has been reported for skin cancer treatment. This current study evaluated eight cases of locally advanced and refractory basal cell or squamous cell cancers which were treated with cetuximab.

Methods: This is a retrospective study on eight patients who had received cetuximab for treatment of cutaneous carcinoma since 2007 at Southern Illinois University School of Medicine (SIU-SOM) Medical Oncology clinic.

Results: Three of the four patients with basal cell carcinoma and two of the four patients with squamous cell carcinoma maintained remission on treatment.. The main side effect was acneiform rash which required termination of treatment for one patient and dose reduction in another.

Conclusion: The study indicates that cetuximab may have a beneficial role for patients with non-melanoma cutaneous carcinomas that are refractory to standard therapy.

Wednesday, August 31, 2016 6:00 PM|S. Curiel-;Olmo, S. Derdak, S. Beltran, M. Santibañez, N. Martínez, A. Castillo-;Trujillo, M. Gut, R. Sánchez-;Pacheco, C. Almaraz, L. Cereceda, B. Llombart, A. Agraz-;Doblas, J. Revert-;Arce, J.A. López Guerrero, M. Mollejo, P.I. Marrón, P. Ortiz-;Romero, L. Fernandez-;Cuesta, I. Varela, I. Gut, L. Cerroni, M.A. Piris, J.P. Vaqué|JournalTOCs API - Journal of Investigative Dermatology (875 articles)|Labels: skin cancer

Shared oncogenic pathways implicated in both virus-positive and UV-induced Merkel Cell Carcinomas
M.C. González-Vela S. Curiel-Olmo, S. Derdak, S. Beltran, M. Santibañez, N. Martínez, A. Castillo-Trujillo, M. Gut, R. Sánchez-Pacheco, C. Almaraz, L. Cereceda, B. Llombart, A. Agraz-Doblas, J. Revert-Arce, J.A. López Guerrero, M. Mollejo, P.I. Marrón, P. Ortiz-Romero, L. Fernandez-Cuesta, I. Varela, I. Gut, L. Cerroni, M.A. Piris, J.P. Vaqué
Journal of Investigative Dermatology, Vol. , No. (2016) pp. -
Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin whose molecular pathogenesis is not completely understood, despite the role that Merkel cell polyomavirus (MCPyV) can play in 55% to 90% of cases. To study potential mechanisms driving this disease in clinically characterized cases, we searched for somatic mutations using whole exome sequencing, and extrapolated our findings to study functional biomarkers reporting on the activity of the mutated pathways. Confirming previous results, MCPyV-negative tumors had higher mutational loads with UV signatures and more frequent mutations in TP53 and RB compared with their MCPyV-positive counterparts.

Wednesday, August 17, 2016 6:00 PM|Julia Zaragoza, Thibault Kervarrec, Antoine Touzé, Martine Avenel-Audran, Nathalie Beneton, Eric Esteve, Ewa Wierzbicka Hainaut, François Aubin, Laurent Machet, Mahtab Samimi|Journal of the American Academy of Dermatology|Labels: skin cancer
The prognostic relevance of a high blood neutrophil-to-lymphocyte ratio (NLR) has been reported in many cancers, although, to our knowledge, not investigated in patients with Merkel cell carcinoma (MCC) to date.
Sunday, July 17, 2016 10:05 PM|McAdam, E., Brem, R., Karran, P.|Molecular Cancer Research recent issues|Labels: skin cancer

The relationship between sun exposure and nonmelanoma skin cancer risk is well established. Solar UV (wavelength 280–400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280–320 nm). How the 20-fold more abundant UVA (320–400 nm) component of solar UV radiation increases skin cancer risk is not understood. Here it is demonstrated that the contribution of UVA to the effect of UV radiation on cultured human cells is largely independent of its ability to damage DNA. Instead, the effects of UVA reflect the induction of oxidative stress that causes extensive protein oxidation. Because NER proteins are among those damaged, UVA irradiation inhibits NER and increases the susceptibility of the cells to mutation by UVB. NER inhibition is a common consequence of oxidative stress. Exposure to chemical oxidants, treatment with drugs that deplete cellular antioxidants, and interventions that interfere with glucose metabolism to disrupt the supply of cellular reducing power all inhibit NER. Tumor cells are often in a condition of oxidative stress and one effect of the NER inhibition that results from stress-induced protein oxidation is an increased sensitivity to the anticancer drug cisplatin.

Implications: As NER is both a defense against cancer and a significant determinant of cell survival after treatment with anticancer drugs, its attenuation by protein damage under conditions of oxidative stress has implications for both cancer risk and for the effectiveness of anticancer therapy. Mol Cancer Res; 14(7); 612–22. ©2016 AACR.

Monday, June 6, 2016 7:00 AM|Unknown Author|Press Release|Labels: PD-1/PD-L1, skin cancer, clinical trial
Dateline City:
  • First pivotal study for Merck KGaA, Darmstadt, Germany, and Pfizer’s investigational anti-PD-L1 antibody avelumab shows clinically meaningful tumor responses in pre-treated metastatic Merkel cell carcinoma (MCC)
  • International, multicenter Phase II study results in metastatic MCC with 88 patients represents largest data set of any anti-PD-L1/PD-1 reported in this patient population
  • Plan to submit to regulatory authorities based on these results

CHICAGO--(BUSINESS WIRE)--Merck KGaA, Darmstadt, Germany, and Pfizer (NYSE: PFE) today announced results from the first pivotal, international, multicenter, open-label, Phase II study of avelumab*, which showed a 31.8% objective response rate (ORR) (28 of 88 patients; 95.9% CI: 21.9–43.1%), in the pre-planned primary analysis of the study, and a manageable safety profile in patients with metastatic Merkel cell carcinoma (MCC) who were treated with avelumab in second or subsequent lines of therapy.


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Thursday, June 2, 2016 10:05 PM|Unknown Author|Cancer Discovery recent issues|Labels: PD-1/PD-L1, skin cancer, clinical trial

In a phase II single-arm study, the PD-1 checkpoint inhibitor pembrolizumab effectively shrank tumors and prolonged survival in more than half of patients with Merkel cell carcinoma. Responses were significantly more durable that those typically seen with chemotherapy.

Thursday, April 28, 2016 9:59 AM|ORNAT, M., KOBIERZYCKI, C., GRZEGRZOLKA, J., PULA, B., ZAMIRSKA, A., BIENIEK, A., SZEPIETOWSKI, J. C., DZIEGIEL, P., OKOLOW, M. P.|Anticancer Research recent issues|Labels: skin cancer

Background/aim: SRY-related HMG box protein 18 (SOX18) is a transcription factor involved in a range of physiological processes, including differentiation of endothelial cells during new vessel formation. Numerous studies are being conducted to determine its role in carcinogenesis. Materials and Methods: Thirty-five cases of squamous cell carcinoma (SCC), 61 cases of basal cell carcinoma (BCC), 15 cases of actinic keratosis (AK) and 15 normal skin (NS) cases were examined in the study. Expression of SOX18 was investigated with immunohistochemistry and light optic microscopy. The obtained results were subjected to statistical analysis including available clinicopathological data. Results: Nuclear expression of SOX18 was shown in vascular endothelial cells, basal layer cells of NS epidermis, as well as in AK, BCC and SCC cancer cells. Expression of SOX18 in SCC, BCC and AK cells was significantly higher than in NS (p<0.01, p<0.001 and p<0.01, respectively). Additionally, higher expression of SOX18 in BCC than in SCC cells (p<0.001) was observed. Conclusion: SOX18 may play a role in the development of BCC and SCC. Further studies with the use of additional markers tested at the mRNA and protein level are necessary for better explanation of SOX18 function in cancer transformation.

Thursday, March 10, 2016 10:28 AM|Mass Device|MedWorm: Nonmelanoma Skin Cancer|Comments|Labels: skin cancer, financial
Sensus Healthcare yesterday set the terms on an initial public offering that would raise $20 million at the mid-point. Boca Raton, Fla.-based Sensus makes the SRT-100 and SRT-100 Vision photon X-ray low-energy superficial radiotherapy systems for treating non-melanoma skin cancers, including basal cell and squamous cell carcinoma. Sensus said it plans to float more than 1.8 million shares at $10 to $12 apiece, working out to a low-end raise of $18.2 million and a high end of $21.8 million. Sensus said it’s won 510(k) clearance from the FDA, CE Mark approval in the European Union and nods from the China Food & Drug Administration and Health Canada and has more than 200 installed SRT-100 devices in 11 countries. The company said it plans to put $3 million of the proceeds toward h...