Lung Cancer/Mesothelioma Cancer TRDG: Meetings and Minutes

Agenda:

  1. The current status of translational research efforts at FCCC and Temple in the particular disease site including the status of Investigator-initiated trials and opportunities based on science and feasibility.
  2. Opportunities for collaboration based on existing ongoing activities or through knowledge of developments in the field.
  3. To exchange information regarding funding opportunities.
  4. To consider multidisciplinary programmatic efforts that may be supported by P01s or SPOREs.
  5. To discuss progress that is being made through more focused presentations by specific investigators or subgroups.
  6. To take full advantage of institutional capabilities and resources in terms of genomics, tissues, CTO, and to integrate across programmatic efforts, basic or clinical research activities and tumor boards.
  7. To bring in additional investigators including lab members/trainees involved in translational research.

The TRDGs strive to recognize and develop opportunities for collaborative translational research directions by providing a focused forum for exchange of information among a diverse group of stake-holders interested in a particular disease site. Before each meeting, depending on the particular expertise, participants are asked to review/be prepared to discuss the current disease site early phase investigational protocols at FCCC, the potential opportunities in industry with available targeted agents, potential collaborations with other institutions that have activated protocols with novel agents, specific molecular targets or signaling pathways for the disease site at FCCC, resistance mechanisms, potential biomarkers that can be incorporated into protocols, and the major open questions for the disease site or other more general questions in the field that could be addressed for the disease site.

  • 9-13-16

    Dr. Margie Clapper spoke about “ Lung cancer among never smokers – a different disease?” Data on lung cancer shows that death rates in women started to decrease as in men but appear to be plateauing. A similar pattern is emerging in deaths from COPD. Non-smoking related lung cancer is not uncommon. In Asian women there is a theory about cooking oil exposure. Air pollution also plays a role. The trends are rising at the UK as well in women who are never smokers with median age of 67%... Expand

  • 4-29-16

    Dr. El-Deiry spoke about an R21 RFA from the NCI on Clinical and Translational Exploratory/Developmental Studies. Dr. Rohit Kumar spoke about “updates in lung cancer screening”. He introduced lung cancer and risk factors with a trend for the group with 1-9 cigarettes per day still rising... Expand

  • 2-9-16

    Dr. Joe Testa spoke about mouse models of malignant mesothelioma. There are frequent alterations in BAP1, CDKN2A and NF2 in malignant mesothelioma. Nat Genet 2011 Marc Ladanyi. p53 mutations are not common, Rb is rarely mutated due to frequent involvement of the p16/ARF locus. LATS1 and LATS2 are mutated. Now exon deletions are being found in BAP1 in mesothelioma. 60-65% of tumors... Expand

  • 12-8-15

    Dr. Erica Golemis spoke about how studying a drug leads to new biology. EMT correlates with poor outcome in lung cancer. She discussed the breakdown of therapeutics for NSCLC in 2015. In 2012 she started working with Synta looking at ganetespib, a HSP90 inhibitor being evaluated in lung cancer. HSP90 has hundreds of clients, many of which are oncoproteins. She mentioned that in general HSP90 inhibitors had retinal and liver toxicity while Ganetespib avoids both of these toxicities. A clinical trial in a broad population failed to show an OS benefit. Dr. Golemis spoke about a 655 gene siRNA library screen in 5 NSCLC lines with KRAS/p53 mutations or EML4-ALK fusions. She identified AMH and AMHR2 from the siRNA screen as genes whose knockdown sensitized the cells. Results were recently published (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956518/). The GNRH receptor pathway was noticed and linked to AMH and AMHR2. Additional experiments in vivo demonstrated sensitization by knockdown in two xenografts. AMH = anti-Mullerian hormone; plays role in development and reproduction in pathways seemingly unrelated to lung cancer. There were previously no reports of AMH in lung cancer but TGF-beta, BMP, and lung cancer suggested why identification of AMH is potentially important. She showed expression of AMH and AMHR2 in NSCLC cells with good antibodies and siRNAs. p-SMAD1,5,8 levels came down with AMH KD. BMPR2 levels rose demonstrating a compensatory growth suppressive pathway induction. SMAD3 phosphorylation was also seen that she attributes to BMPR2. AMH or AMHR2 KD prompted EMT with appropriate marker changes. This depletion stimulates invasion. She further showed that induction of EMT depletes AMH, AMHR2 and suggested that the mesenchymal state may sensitize to ganetespib. Dr. Golemis mentioned that AMH depletion or mesenchymal state leads to cisplatin resistance. She further stated that TCGA data shows high AMH/AMHR2 correlates with favorable DFS in lung cancer. She discussed her model and therapeutic implications. There was discussion of recent papers looking at EMT, metastasis and drug sensitivity.

  • 9-29-15

    There was discussion of an NCCN grant opportunity. The “Opportunity blood collection protocol” is open and available to look at blood components or CTCs. Dr. Hoss Borghaei spoke about NA-NOSE (breath analysis using hand held device) early stage pre and post surgery; mutation analysis may be possible through CGI... Expand

  • 5-26-15

    Dr. Margie Clapper spoke about estrogen metabolism and its modulation within the lung. She recently spoke about this topic at Temple. Drs. Edna Cukierman, Hoss Borghaei and Margie Clapper speak regularly at COPD rounds led by Dr. Criner at Temple. Dr. Clapper started in the 1990’s on lung cancer with increasing lung cancer cases being seen at that time. Rates have fallen in men over time but the same was not observed in women. However decreased smoking was observed in both men and women. Over the last 30 years there has been a rise in death rates from COPD but women have more deaths for unclear reasons. Nonsmoking lung cancer is now the 7th leading cause of death world-wide and has also been increasing... Expand

  • 5-4-15

    Dr. Joseph Testa spoke about malignant mesothelioma (MM) models for pathogenesis and therapy. He discussed work with Verastem on a novel FAK inhibitor... Expand

  • 2-3-15

    Dr. Hoss Borghaei described clinical trials that emerged from working with Dr. Erica Golemis and mentioned prevention trials and some challenges. There is not enough critical mass in lung cancer and there is a need for more translational researchers... Expand

  • 12-11-14

    Dr. El-Deiry introduced the TRDG, welcomed the attendees at the meeting and went over the standing Agenda that was circulated in the initial invitation and in the email with the schedule for the meeting. It was discussed that various meeting formats going forward would be used including the round-table as well as more focused presentations by individuals or sub-groups. This meeting is scheduled every two months and we plan to change the time from Thursday to Tuesday to maximize group participation. It was discussed that the membership of the group will very likely evolve over time and the attendees at this first meeting were asked to suggest participation by those who may be interested... Expand

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